The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index; 47 of the 106 sources its claims cite were checked for support.
Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome
Open accessAbstract
Mast cell activation syndrome (MCAS) is a condition characterized by recurrent episodes of clinically relevant, systemic, severe reactions to mast cell (MC)-derived mediators released in the context of anaphylaxis or another acute MC-related event. It is important to document MC involvement in these reactions in order to establish the diagnosis MCAS. The most specific and reliable marker of systemic MC activation is an acute and substantial event-related (transient) increase in the serum tryptase level over the individual's baseline value. However, the baseline level of tryptase varies depending on the underlying disease and the genetic background. For example, an estimated 3-5% of healthy individuals exhibit duplications or multiple copies of the TPSAB1 gene encoding for alpha-tryptase, and over 30% of all patients with myeloid neoplasms, including mastocytosis, have elevated basal tryptase levels. Therefore, it is of utmost importance to adjust the event-related diagnostic (MCAS-confirming) increase in tryptase over the individual baseline in a robust approach. To address this challenge, the 20% + 2 formula was proposed by the consensus group in 2012. Since then, this approach has been validated in clinical practice by independent groups and found to be sound. In the current article, we discuss the emerging importance and value of the 20% + 2 formula in clinical practice and its role as a criterion of severe systemic MC activation and MCAS.
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Claims the paper makes
17 Partly supported · 8 No full text of the sources · 7 Own interpretation · 5 No basis given · 1 Supported · 1 Couldn’t confirm · 1 Own result · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“tryptases account for >20% of the total protein content in tissue MC [9].”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Introduction
What the sources say
- Partly supportedcites [9] sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) describes human β-tryptase as abundant in mast cells. It does not state that tryptases exceed 20% of total protein in tissue mast cells, so the numerical claim is unsupported by our copy. (LLM, conf=0.82)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the most specific and reliable marker of systemic MC activation is an acute and substantial event-related (transient) increase in the serum tryptase level over the individual’s baseline value.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Abstract
What the sources say
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
The Introduction reports that serum or plasma tryptase rises during insect-sting anaphylaxis and correlates with reaction severity; the Results also note preliminary evidence of increases during mast-cell-mediator attacks. But the paper does not establish that a transient rise over an individual’s own baseline is the most specific and reliable marker of systemic mast-cell activation. Page numbers are unavailable in our copy. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [13] source
- Not checked — no full text of the sourcecites [14] source
- Partly supportedcites [15] sourceExperimental — accuracy not yet measured
The Abstract says elevated β-tryptase may be more specific for mast-cell activation than total tryptase, and the Discussion explains that β-tryptase is released when mast cells degranulate. But the Methods define elevated total tryptase using a fixed cutoff, not a rise over each patient’s baseline. The Discussion also says the clinical role of β-tryptase needs further study; it does not establish a transient baseline-relative rise as the most reliable marker. (LLM, conf=0.86)
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Introduction says tryptase selectively indicates mast-cell activation, and the Results show an event-related rise followed by a decline after venom challenge. But the paper does not establish that a substantial rise in serum tryptase over an individual’s own baseline is the most specific and reliable marker; its before-and-after challenge measurements used plasma, and its Methods describe fixed ranges for elevated levels. No page numbers are available in our copy. (LLM, conf=0.85)
- Partly supportedcites [17] sourceExperimental — accuracy not yet measured
In the proposed diagnostic criteria section (page unavailable), the paper says tryptase rises transiently during mast cell activation and recommends comparing levels measured during symptoms with the patient’s baseline. It does not establish that a substantial rise in tryptase is the most specific and reliable indicator compared with other mast-cell mediators, which it also recommends measuring. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [18] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the baseline level of tryptase varies depending on the underlying disease and the genetic background.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Abstract
What the sources say
- Not checked — no full text of the sourcecites [25] source
- Not checked — no full text of the sourcecites [26] source
- Partly supportedcites [27] sourceExperimental — accuracy not yet measured
In “Cellular origin, historical overview and development of the test” (page unavailable), the paper reports that basal tryptase is usually elevated in systemic mastocytosis but normal in most cases of cutaneous mastocytosis, supporting variation by underlying disease. The searched passages do not establish that a person’s genetic background independently determines baseline tryptase; the mention of elevated levels in familial mast-cell activation syndromes does not make that broader point. (LLM, conf=0.82)
- Partly supportedcites [28] sourceExperimental — accuracy not yet measured
In “To the Editor” (page not provided), the authors report elevated basal tryptase segregating in nine families with an autosomal dominant inheritance pattern, supporting the genetic-background part of the claim. They associate elevated tryptase with clinical features but do not establish that baseline concentrations vary according to the underlying disease; they say whether the elevation is primary or secondary remains under investigation. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [29] source
- Partly supportedcites [30] sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) links increased TPSAB1 copy number to elevated basal serum tryptase and describes a gene-dose effect in hereditary α-tryptasemia. This supports variation with genetic makeup, but the paper does not establish that baseline levels vary across underlying diseases generally. (LLM, conf=0.83)
- Not checked — no full text of the sourcecites [31] source
- Not checked — no full text of the sourcecites [32] source
- Not checked — no full text of the sourcecites [33] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“over 30% of all patients with myeloid neoplasms, including mastocytosis, have elevated basal tryptase levels.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Abstract
What the sources say
- Not checked — no full text of the sourcecites [25] source
- Not checked — no full text of the sourcecites [26] source
- Partly supportedcites [27] sourceExperimental — accuracy not yet measured
The section “Elevated basal serum tryptase levels are frequently detected in patient with myeloid neoplasms” (page not provided) reports elevated levels in more than 90% of patients with systemic mastocytosis, about 30–40% with AML, and about 30–35% with CML. It says the incidence is lower in MPN and MDS and gives no rate for all myeloid neoplasms combined, so it does not establish the claimed overall figure of over 30%. (LLM, conf=0.86)
- Could not verifycites [28] sourceExperimental — accuracy not yet measured
The 'To the Editor' section reports elevated basal tryptase in families with inherited tryptasemia and says that the patients assessed did not meet criteria for systemic mastocytosis. Searches for myeloid neoplasms and a prevalence above 30% found no passage in our copy addressing that claim; no page number is provided for the section. (LLM, conf=0.75)
- Not checked — no full text of the sourcecites [29] source
- Could not verifycites [30] sourceExperimental — accuracy not yet measured
The Introduction links increased TPSAB1 copy number to elevated basal serum tryptase, and the Subjects section mentions mastocytosis study protocols. Neither passage reports the proportion of patients with myeloid neoplasms who have elevated basal tryptase. Searches for myeloid neoplasms, mastocytosis, and the claimed 30% prevalence found no supporting passage in our copy; page numbers were not provided. (LLM, conf=0.73)
- Not checked — no full text of the sourcecites [31] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“the 20% + 2 formula was proposed by the consensus group in 2012.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Abstract
What the sources say
- Supportedcites [21] source
The main text says an international consensus group introduced the MCAS diagnostic criteria and identifies the 20% over baseline plus 2 ng/mL tryptase threshold as the second criterion. The References section lists a 2012 consensus proposal among the works cited for those criteria. (LLM, conf=0.87)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“an estimated 3–5% of healthy individuals exhibit duplications or multiple copies of the TPSAB1 gene encoding for alpha-tryptase”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Abstract
What the sources say
- Partly supportedcites [30] sourceExperimental — accuracy not yet measured
The Results report increased α-tryptase-encoding TPSAB1 copies, and the section on the ClinSeq cohort describes identifying such copies in some healthy adults. But the reported 3.0% frequency refers to a coinherited variant haplotype, not TPSAB1 duplications; the paper says duplications could not be assessed by that method. These passages do not establish the claimed 3–5% prevalence among healthy people (page numbers unavailable). (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [31] source
- Not checked — no full text of the sourcecites [32] source
- Not checked — no full text of the sourcecites [33] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“the risk of MCAS does not appear to increase with higher serum tryptase levels [43–46].”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Conditions Associated with an Elevated Baseline Serum Tryptase Level
What the sources say
- Not checked — no full text of the sourcecites [43] source
- Not checked — no full text of the sourcecites [44] source
- Could not verifycites [45] sourceExperimental — accuracy not yet measured
The Results report higher baseline tryptase in patients with clonal mast cell disorders, and the Discussion associates levels of at least 7.95 ng/mL with risk of systemic mastocytosis. These are not findings about MCAS risk: the paper identifies only one patient with monoclonal mast cell activation syndrome and does not assess whether MCAS risk changes as tryptase rises. (LLM, conf=0.75)
- Could not verifycites [46] sourceExperimental — accuracy not yet measured
The Introduction describes tryptase as a marker used in diagnosing mast-cell activation and MCAS, while the Results report tryptase changes during anaphylaxis in mastocytosis patients. Neither section assesses whether higher serum tryptase levels are associated with the risk of developing MCAS; searches for that relationship found no passage addressing it. Page numbers were unavailable in our copy. (LLM, conf=0.76)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Thus, a number of genetic, inflammatory, and neoplastic conditions are associated with an increased basal serum tryptase level.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Conditions Associated with an Elevated Baseline Serum Tryptase Level
What the sources say
- Not checked — no full text of the sourcecites [25] source
- Not checked — no full text of the sourcecites [26] source
- Partly supportedcites [27] sourceExperimental — accuracy not yet measured
The sections on myeloid neoplasms and tryptase screening (pages not provided) link elevated basal tryptase to several neoplasms and say it may occur in familial mast-cell activation syndromes. The section on healthy individuals says levels may rise slightly during chronic active helminth infection, but remain stable during viral or bacterial infections and other inflammatory processes. The claim is therefore supported for the neoplastic and familial examples but overgeneralizes the inflammatory association. (LLM, conf=0.84)
- Partly supportedcites [28] sourceExperimental — accuracy not yet measured
In “To the Editor” (page not specified), the paper reports elevated basal tryptase inherited in nine families and associated with atopic and gastrointestinal conditions, including eosinophilic gastrointestinal disease. It discusses systemic mastocytosis, but excludes that diagnosis in the patients evaluated; it does not establish the broader claim that a number of neoplastic conditions are associated with raised basal tryptase. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [29] source
- Partly supportedcites [30] sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) links increased TPSAB1 copy number, a genetic condition, to elevated basal serum tryptase. The paper does not link inflammatory or neoplastic conditions to elevated basal serum tryptase, so it supports only the genetic part of the claim. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [31] source
- Not checked — no full text of the sourcecites [32] source
- Not checked — no full text of the sourcecites [33] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“during and shortly after a severe anaphylactic event where MC release large amounts of tryptase, the serum tryptase level increases substantially over the individual’s baseline (Fig. 1) [12–17].”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Introduction
What the sources say
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
The Introduction says serum or plasma tryptase is measurable during insect-sting systemic anaphylaxis and correlates with reaction severity. The Results describe serum collected 60 minutes after onset of a hypotensive reaction, and the Discussion distinguishes tryptase released by degranulation from tryptase present at baseline. The paper does not show that these patients’ acute levels rose substantially above their own measured baselines. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [13] source
- Not checked — no full text of the sourcecites [14] source
- Partly supportedcites [15] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says tryptase elevations are believed to begin about one hour after mast-cell stimulation, and reports elevated tryptase in some patients with acute allergic reactions. It also says many patients in this study did not have severe anaphylaxis. The paper does not establish a substantial rise over each individual's baseline during or shortly after a severe event. (LLM, conf=0.84)
- Supportedcites [16] source
The Results report that tryptase rose after experimentally induced anaphylactic reactions, reaching a maximum at 1–2 hours, and that a patient presenting with systemic anaphylaxis had a markedly elevated serum level. The Abstract notes that the rise may not be detectable in the first 15–30 minutes, so it is not necessarily immediate. (LLM, conf=0.90)
- Partly supportedcites [17] sourceExperimental — accuracy not yet measured
The Proposed Criteria section says serum tryptase should be measured within four hours of symptom onset, compared with the patient’s baseline, and rises transiently during mast-cell activation. It identifies anaphylaxis as a mast-cell activation disorder, but does not establish that the rise during a severe anaphylactic event is necessarily substantial. (LLM, conf=0.83)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“tryptase has been repeatedly described as the most specific and reliable biomarker of severe systemic MC activation in daily practice [12–18].”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Introduction
What the sources say
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
The Introduction (page not provided) says tryptase is concentrated in mast cells and that blood levels correlate with the severity of insect-sting-induced systemic anaphylaxis. This supports its use as a marker of systemic mast-cell activation, but the paper does not establish that it is the most specific and reliable biomarker compared with others, or assess its reliability in daily practice. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [13] source
- Not checked — no full text of the sourcecites [14] source
- Partly supportedcites [15] sourceExperimental — accuracy not yet measured
The Abstract says elevated β-tryptase may be more specific for mast-cell activation than total tryptase. But the Discussion reports that histamine or total tryptase elevations were more strongly associated with signs such as hypotension and wheezing, and says β-tryptase’s clinical role needs further study. The paper therefore does not establish tryptase as the most reliable biomarker of severe systemic activation in daily practice. Page numbers are unavailable in our copy. (LLM, conf=0.86)
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Introduction (page not provided) says tryptase selectively indicates mast-cell activation and is more clinically practical to measure than histamine; the Discussion describes cases where testing helped confirm anaphylaxis. The paper does not establish that tryptase is the most specific and reliable biomarker in daily practice, and it notes that elevations may be missed early after a reaction. (LLM, conf=0.85)
- Partly supportedcites [17] sourceExperimental — accuracy not yet measured
The proposed diagnostic criteria section (page unavailable) identifies serum tryptase as a test for documenting mast cell activation during symptomatic episodes. It also lists other mediator tests and does not establish that tryptase is the most specific or reliable biomarker for severe systemic activation in daily practice. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [18] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
- Probably not a substantial claim. 7
- It may state two separate claims as one. 13
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“documented recurrent episodic occurrence of typical systemic symptoms that are produced by MC mediators and involve at least 2 organ systems”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Introduction
What the sources say
- Partly supportedcites [19] sourceExperimental — accuracy not yet measured
The Clinical Symptoms section (p. 3) says recurrent symptoms involving two or more organ systems increase the likelihood of systemic mast cell activation. It also says symptoms alone are not diagnostic; the Definition and Proposed MCA Criteria section (p. 3) requires evidence of increased mast-cell mediators and generally a response to mediator-targeting treatment. The claim therefore describes a clinical criterion but overstates it as sufficient for an MCAS diagnosis. (LLM, conf=0.88)
- Partly supportedcites [21] sourceExperimental — accuracy not yet measured
The paper’s diagnostic-criteria passage identifies episodic mast-cell-related symptoms affecting two or more organ systems as the first criterion. It also requires a specified rise in serum tryptase and improvement with mast-cell-targeting treatment, so the symptoms alone do not establish an MCAS diagnosis. (LLM, conf=0.86)
- Partly supportedcites [22] sourceExperimental — accuracy not yet measured
The “Symptoms Produced by Systemic MCA” section describes severe, recurrent symptoms affecting more than one organ or tissue, supporting the symptom pattern in the claim. But “Consensus Criteria and Classification of MCAS” says diagnosis also requires biochemical evidence of mast-cell involvement and a response to mediator-targeting treatment; the symptoms alone do not establish MCAS. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“After in-depth deliberations and based on shared practical experience, the faculty did come up with a consensus proposal and put forth the 20% + 2 formula during the Working Conference [21].”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Scientific and Conceptual Basis of the 20% + 2 Formula
What the sources say
- Partly supportedcites [21] sourceExperimental — accuracy not yet measured
The paper’s main text says an international consensus group met and introduced MCAS diagnostic criteria, including a serum tryptase increase of 20% over baseline plus 2 ng/mL. It does not say the formula was put forth at a Working Conference or describe the group’s deliberations and shared practical experience. No page numbers are provided in our copy. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These include tryptase gene replications such as hereditary alpha tryptasemia; chronic infections, such as helminth infections; renal insufficiency – especially hemodialysis patients; and myeloid neoplasms, including myelodysplastic syndromes, SM, acute myeloid leukemia, chronic myeloid leukemia (CML), and chronic eosinophilic leukemia [25–33].”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Conditions Associated with an Elevated Baseline Serum Tryptase Level
What the sources say
- Not checked — no full text of the sourcecites [25] source
- Not checked — no full text of the sourcecites [26] source
- Partly supportedcites [27] sourceExperimental — accuracy not yet measured
The sections on healthy individuals and myeloid neoplasms report elevated tryptase with chronic active helminth infection, renal failure, and each listed neoplasm. The References section names a study of raised baseline tryptase in hemodialysis patients. Our copy does not identify tryptase gene replication or hereditary alpha tryptasemia as a cause. (LLM, conf=0.88)
- Partly supportedcites [28] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [29] source
- Supportedcites [30] source
The Introduction states that increased α-tryptase-encoding TPSAB1 copy number is linked to elevated basal serum tryptase and identifies the condition as hereditary α-tryptasemia syndrome. This supports the hereditary α-tryptasemia example for which this paper is relevant within the citation range; the sentence does not individually attribute the other listed conditions to this source. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [31] source
- Not checked — no full text of the sourcecites [32] source
- Not checked — no full text of the sourcecites [33] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“although it was clear that tryptase is the biomarker of choice to define anaphylaxis and thus MCAS based on previous literature data and experience in specialized centers [12–18], a diagnostic threshold was missing.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Scientific and Conceptual Basis of the 20% + 2 Formula
What the sources say
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) describes tryptase measurements during insect-sting anaphylaxis that correlate with reaction severity, supporting its use as an anaphylaxis marker. The paper does not establish it as the biomarker of choice for defining anaphylaxis or MCAS, or address whether a diagnostic threshold for those conditions was missing. Its threshold discussion concerns baseline tryptase in mastocytosis, not diagnosis of anaphylaxis or MCAS. (LLM, conf=0.83)
- Not checked — no full text of the sourcecites [13] source
- Not checked — no full text of the sourcecites [14] source
- Partly supportedcites [15] sourceExperimental — accuracy not yet measured
The Introduction and Discussion describe tryptase as a potential marker of mast-cell activation, but do not establish it as the biomarker of choice for anaphylaxis or MCAS; the Discussion says its clinical role needs further study. The Methods use a cutoff for elevated total tryptase, but do not establish a diagnostic threshold for either condition. (LLM, conf=0.82)
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Introduction and Discussion describe circulating tryptase as a useful, relatively selective indicator of mast-cell activation and report its clinical use in suspected anaphylaxis. The paper does not discuss MCAS or establish tryptase as its biomarker of choice. Its Methods give ranges for normal and elevated tryptase, so it does not support an unqualified claim that no threshold existed, although it does not set out a diagnostic threshold for MCAS. (LLM, conf=0.85)
- Partly supportedcites [17] sourceExperimental — accuracy not yet measured
In “Proposed Criteria for the diagnosis of idiopathic mast cell activation syndrome” (page unavailable), the paper identifies serum tryptase as a test for mast-cell activation, calls for comparison with baseline, and says objective diagnostic guidelines lacked consensus. It does not call tryptase the biomarker of choice over other mediators, and it gives a conditional >15 ng/ml criterion rather than saying no diagnostic threshold of any kind existed. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [18] source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“one of the deliberation points was the minimal increase in serum tryptase over the individual’s baseline that would meet the criterion of a significant systemic MC activation and would thus count as a diagnostic marker of MCAS [21].”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Scientific and Conceptual Basis of the 20% + 2 Formula
What the sources say
- Partly supportedcites [21] sourceExperimental — accuracy not yet measured
The main text (page unavailable) says a consensus group met to establish MCAS diagnostic criteria and identifies a serum tryptase rise of 20% above baseline plus 2 ng/mL as one criterion. It does not identify a 2010 Working Conference or say that determining the minimum rise was a specific deliberation point. (LLM, conf=0.84)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“when taking the 11.4 threshold as denominator, an increased basal tryptase level is found frequently in otherwise healthy individuals (roughly 5–10% of the general population), in diverse reactive states, and in hematologic disorders, especially in myeloid malignancies (roughly 20–30%; Table 2) [25–31].”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Conditions Associated with an Elevated Baseline Serum Tryptase Level
What the sources say
- Not checked — no full text of the sourcecites [25] source
- Not checked — no full text of the sourcecites [26] source
- Partly supportedcites [27] sourceExperimental — accuracy not yet measured
In “Total serum tryptase levels in healthy individuals” (page unavailable), the paper recognizes 11.4 ng/mL as a cutoff used by many centers and says many healthy people have levels between 10 and 15 ng/mL, but it does not give a 5–10% prevalence above 11.4 ng/mL. In “Elevated basal serum tryptase levels are frequently detected in patient with myeloid neoplasms” (page unavailable), it reports elevations in several myeloid disorders, but gives disease-specific figures measured against >15 ng/mL rather than an overall 20–30% figure at 11.4 ng/mL. It mentions some nonmalignant causes of increases, while saying infections and other inflammatory processes generally leave levels stable. (LLM, conf=0.85)
- Could not verifycites [28] sourceExperimental — accuracy not yet measured
The To the Editor section reports elevated basal tryptase in nine families referred for allergic disease or suspected mastocytosis; it does not establish how frequently elevated levels occur in otherwise healthy people. Searches for the 11.4 ng/mL threshold, the 5–10% and 20–30% estimates, reactive states, and myeloid malignancies found no passage supporting those claims in our copy. (LLM, conf=0.76)
- Not checked — no full text of the sourcecites [29] source
- Could not verifycites [30] sourceExperimental — accuracy not yet measured
The Introduction links increased TPSAB1 copy number to elevated basal serum tryptase, and the ClinSeq methods describe measuring tryptase in healthy adults. Neither those passages nor searches for the 11.4 ng/mL threshold, population prevalence, reactive states, or myeloid malignancies establish the frequencies claimed; the paper’s reported screening threshold is >8 ng/mL. (LLM, conf=0.72)
- Not checked — no full text of the sourcecites [31] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“a documented clinically meaningful response to drugs that either target MC-derived mediators (e.g., H1 antihistamines or antileukotrienes) and/or suppress MC activation (e.g., cromoglycate, ketotifen, or omalizumab) [19, 21, 22].”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Introduction
What the sources say
- Partly supportedcites [19] sourceExperimental — accuracy not yet measured
The Definition and Proposed MCA Criteria (p. 3) includes an objective major response to drugs affecting mast-cell mediators as one diagnostic criterion, and Response to Therapy (p. 4) names histamine receptor blockers, leukotriene receptor blockers and cromolyn. The paper requires clinical symptoms and a mediator increase as well; it does not establish a drug response alone as sufficient for diagnosis or name ketotifen or omalizumab among the examples. (LLM, conf=0.85)
- Supportedcites [21] source
In the paper’s discussion of consensus diagnostic criteria (page unavailable), the third criterion is a clear improvement in symptoms with drugs targeting mast-cell-derived mediators, mast-cell-stabilizing agents, or both. The paper also requires the first two criteria; it does not present treatment response alone as sufficient for diagnosis. (LLM, conf=0.91)
- Supportedcites [22] source
The Consensus Criteria and Classification of MCAS section identifies response to mast-cell-stabilizing or mediator-targeting drugs as a diagnostic criterion. It also states that severe recurrent symptoms and biochemical evidence are required; treatment response alone does not establish MCAS. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Later, the 20% + 2 formula was further validated in independent case series – see below.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Scientific and Conceptual Basis of the 20% + 2 Formula
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 20% + 2 formula was subsequently validated against the available literature and all retrospective cases published, and the formula was found to be applicable and robust both in the context of allergy and in the context of mastocytosis (K.B., L.B., and P.V., unpublished observation)”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Scientific and Conceptual Basis of the 20% + 2 Formula
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Whereas mature tryptases are mostly stored in the heparin-containing metachromatic granules of human MC, the precursor forms (pro-tryptases) are released spontaneously and constantly from resting MC [10, 11].”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Since then, this approach has been validated in clinical practice by independent groups and found to be sound.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Abstract
What the sources say
- Not checked — no full text of the sourcecites [48] source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on a constant release rate in the steady state and the chemical and biological stability of tryptases, the resulting basal serum tryptase level is remarkably consistent in healthy individuals.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Introduction
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In other cases, a constantly increased basal release or an extra amount of alpha tryptase gene copies can lead to a persistently elevated basal tryptase – again, however, such persistently elevated tryptase is not an indication of systemic MC activation or MCAS.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Scientific and Conceptual Basis of the 20% + 2 Formula
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“Thereafter, the tryptase level returns to baseline, which may take several hours (up to 24 h), providing a reliable diagnostic window of about 2–4 h for laboratory investigations [18].”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Introduction
What the sources say
- Not checked — no full text of the sourcecites [18] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Employing only an absolute amount of extra tryptase as criterion (e.g., plus extra 20 ng/mL) would fail in those who have very low basal tryptase levels (1–5 ng/mL) and in those with systemic mastocytosis (SM) with a tryptase level exceeding 100 or 200 ng/mL.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Scientific and Conceptual Basis of the 20% + 2 Formula
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, these markers may qualify as criteria for less severe forms of MC activation or as indicators of targets of therapeutic intervention (PGD2), but not as a robust criterion for MCAS.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Are There Alternative Biochemical Parameters Available?
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 20% + 2 consensus equation is a sound tool to measure a clinically relevant increase in tryptase independent of the baseline level, including individuals with normal/low tryptase (<10 ng/mL), those with slightly elevated tryptase (<50 ng/mL) and those with clearly or even massively elevated tryptase.”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Summary and Future Perspectives
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“More recently, diamino-oxidase, a histamine-degrading enzyme, has been described as a marker that increases in MCAS patients and has a similar specificity and time course compared to serum tryptase levels [48].”
§ Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome > Are There Alternative Biochemical Parameters Available?
What the sources say
- Not checked — no full text of the sourcecites [48] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
Many users are unfamiliar with the 20% + 2 formula and ask questions about it and why it was proposed in the MCAS context.
“many users are not familiar with this approach and ask questions related to this formula and why it has been proposed in the MCAS context.”
The paper relies on this without support.
There is ongoing discussion about the use and usefulness of the MCAS criteria in daily practice.
“there remains an ongoing discussion on their use and usefulness in daily practice.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These criteria were developed by consensus based on literature review and expert opinion, have been validated, and are considered standard.6–9”
From Mast cell activation syndrome: Current understanding and research needs (2024) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Tryptase has proven to be a very useful and specific marker to demonstrate mast cell activation and degranulation when an acute (i.e., within 4 h after the event) and baseline value (i.e., at least 24 h after the event) are compared and meet the consensus formula (i.e., an increase of 20% + 2).”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [10]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This approach has been validated and is broadly accepted.”
From Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review (2021) · cites this paper as [44]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“According to the consensus formula, an aST ≥ [(1.2 × bST) + 2], depicts MCA [10,11].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“A tryptase > 20 ng/mL serves as a minor criterion to diagnose systemic mastocytosis and an increase in tryptase > 20% + 2 during an acute event is a required criterion in the diagnosis of mast cell activation syndrome.”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“Overall, the most used and validated approach is the consensus formula.”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“For the time being, the consensus formula is still widely used as a criterion and considered as the golden standard [10].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“This so-called “20% + 2 formula” was subsequently validated by several studies (31–33).”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [33]
In the citing paper
“MCAS is defined by severe recurrent systemic symptoms related to MCA, which resemble anaphylaxis.8,9,13”
From Mast cell activation syndrome: Current understanding and research needs (2024) · cites this paper as [8]
In the citing paper
“Systemic MCA may be documented by an increase in the serum tryptase level by 20% above the individual’s baseline level + 2 ng/mL.8,13”
From Mast cell activation syndrome: Current understanding and research needs (2024) · cites this paper as [8]
In the citing paper
“The event-related increase in serum tryptase levels over baseline is the most specific marker of MCA.6–8”
From Mast cell activation syndrome: Current understanding and research needs (2024) · cites this paper as [8]
In the citing paper
“Lifetime risk of anaphylaxis in mastocytosis is significantly increased in adults (approximately 49%). 120,121”
From Sinus Tachycardia: a Multidisciplinary Expert Focused Review (2022) · cites this paper as [120]
Citations
Cites
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Anaphylaxis and Mast Cell Disease: What Is the Risk?
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Self-citation
Metadata
- Authors
- Valent, P., Bonadonna, P., Hartmann, K., Broesby-Olsen, S., Brockow, K., Butterfield, J. H., Triggiani, M., Lyons, J. J., Oude Elberink, J. N. G., Arock, M., Metcalfe, D. D., & Akin, C.
- Affiliations
- Ludwig Boltzmann Institute for Hematology and Oncology (AT)
- Azienda Ospedaliera Universitaria Integrata Verona (IT)
- University of Basel (CH)
- Technical University of Munich (DE)
- Mayo Clinic (US)
- University of Salerno (IT)
- National Institutes of Health (US)
- Pitié-Salpêtrière Hospital (FR)
- University of Michigan (US)
- ORCID
- Venue
- International Archives of Allergy and Immunology
- Publisher
- S. Karger AG
- Published
- 2019
- Volume
- 180
- Issue
- 1
- Pages
- 44-51
- ISSN
- 1018-2438 (ISSN-L)
- 1423-0097
- PMC
- PMC7115850
- OpenAlex
- W2953893361
- Cited by
- 146
- References
- 58
- Citations by year
- 2026: 21 · 2025: 12 · 2024: 20 · 2023: 17 · 2022: 29 · 2021: 23 · 2020: 18 · 2019: 3
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Archives of Allergy and Immunology (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (acceptedVersion, other-oa)
- PubMed Central (acceptedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, other-oa)
- edoc (University of Basel) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Pfizer
- Universität Basel
- Austrian Science Fund (#F4704-B20, F4701, F4701-B20)
- National Institute of Allergy and Infectious Diseases
- NHLBI Division of Intramural Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Keywords
- mast cell activation syndrome, tryptase, serum tryptase, mast cell activation, anaphylaxis, mastocytosis, diagnostic criteria
- MeSH terms
- Anaphylaxis, Humans, Mast Cells, Mastocytosis, Reference Values, Sensitivity and Specificity, Reproducibility of Results, Biomarkers, Tryptases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-28, under version 3 of the claim definition (prompt extract-v3).
A second model labelled each claim on 2026-09-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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