NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation, and hyperinflammation

Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

Checked by a reasoning model — may be wrong.

The Clinical phenotype section (Table 1; page unavailable) reports protective tetanus antibody titers for both patients studied. The same section reports that both patients were EBV-IgG seropositive. These findings contradict the attributed claim of impaired vaccine- or EBV-specific antibody production in six patients; this paper describes two patients, not six. (LLM, conf=0.85)

Checked by a reasoning model — may be wrong.

The Introduction reports that human NCKAP1L mutations cause immunodeficiency, lymphoproliferation, and inflammation, and discusses immune defects in Nckap1l-deficient mice. But the Results and discussion section describes the mouse defect as a premature stop codon produced by mutagenesis, not a HEM1 deletion. Page numbers are not available in our copy. (LLM, conf=0.85)

In Results and discussion, the immunological-phenotype section reports increased activation and senescence markers in patient CD8+ T cells, with similar but less pronounced findings in CD4+ T cells. The transcriptomics section reports activated T-cell exhaustion signaling pathways in patient blood cells, but does not establish exhaustion separately in CD4+ and CD8+ cells. The paper discusses DOCK8 deficiency in relation to NK-cell killing, not a closely resembling T-cell exhaustion or senescence phenotype. (LLM, conf=0.88)

The Results and discussion section (‘Immunological phenotype of NCKAP1L-deficient patients’; page not provided) reports a slight increase in naïve B cells in both patients and an abnormal proportion of CD19+CD21− B cells in only one patient, consistent with a less consistent subset finding. It links CD19+CD21− cells to autoimmunity, but does not report the specified CD19+CD21loCD38lo innate-like memory subset. (LLM, conf=0.86)

The Clinical phenotype section reports mild anemia with anisopoikilocytosis in patient 1 and anisopoikilocytosis in patient 2. Table 1 shows that patient 1's mean corpuscular volume was within the listed normal range, while patient 2 had microcytosis with severe anemia at age 9 and a normal hemoglobin value at age 11. Thus, the paper supports anisopoikilocytosis and anemia, but not the combined description of mild microcytic anemia in these patients. (LLM, conf=0.87)

The Clinical phenotype table reports elevated CD4+ central-memory and effector-memory percentages in both patients relative to their reference ranges. CD4+ TEMRA percentages, however, fall within those ranges (3% versus 0–5%, and 1% versus 1–2%). The paper studied two patients, so it also does not establish how frequently this pattern occurs among HEM1-deficient patients. (LLM, conf=0.90)

Table 1 (Clinical phenotype; page not provided) shows markedly reduced proportions of naïve CD4+ and CD8+ T cells in both NCKAP1L/HEM1-deficient patients compared with reference ranges. The Clinical phenotype and Immunological phenotype sections report a high antinuclear-antibody titer in one patient, but do not establish severe autoimmune features in both patients, so that qualifier is not supported by this source. (LLM, conf=0.85)

In Results and discussion > Clinical phenotype (page not provided), Patient 2 had recurrent otitis media, sinopulmonary infections, and viral illnesses including upper respiratory infections. Patient 1 is described as developing BCG lymphadenitis, not recurrent infections; the cited paper therefore does not support “all patients.” The cited passages also do not report pneumonia or abscesses. (LLM, conf=0.88)

The Clinical phenotype section reports that patient 2 had gastroenteritis among recurrent viral illnesses and low-titer Epstein–Barr virus viremia. It does not report disseminated herpes simplex virus infection; searches for that term found no supporting passage in our copy. Page numbers were not available. (LLM, conf=0.90)

The Results and discussion, Clinical phenotype section reports formal HLH diagnoses in two NCKAP1L-deficient patients, with fever or splenomegaly and elevated ferritin, triglycerides, and soluble IL-2 receptor. It does not report three such patients or identify hypofibrinogenemia among their diagnostic features. Page numbers are unavailable in our copy. (LLM, conf=0.90)

In the Clinical phenotype table (Table 1), naïve CD8+ T-cell percentages are low in both patients relative to their reference ranges. But the Immunological phenotype section reports increased percentages of CD8+ memory subsets, rather than concluding that CD8+ memory cells show no consistent pattern; the table does show variation between patients for central and effector memory subsets. (LLM, conf=0.85)

Table 1 in the Clinical phenotype section shows an elevated CD19+ B-cell count for patient 1 at one measurement, while the other reported counts are within their stated normal ranges. The paper reports two patients, not nine, and does not establish that six of nine had increased total B cells. (LLM, conf=0.88)

The Clinical phenotype section (page unavailable) reports transaminitis in patient 2 and sinusoidal dilatation in his liver tissue. This paper describes two HEM1-deficient patients, not three, so it does not by itself support the claim about all three patients. (LLM, conf=0.88)

Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

The Clinical phenotype section reports a high antinuclear antibody titer in patient 1, and the Immunological phenotype section describes a B-cell finding associated with lupus. However, the Clinical phenotype table records anti-dsDNA antibodies as negative in both patients, and the passages do not report immune-complex glomerulonephritis. (LLM, conf=0.88)

The Results and discussion (page unavailable) report impaired F-actin polymerization in NCKAP1L-deficient T cells and normal or sometimes increased degranulation markers. They do not establish that loss of a mechanical actin barrier causes vesicular hypersecretion; cytotoxicity remained normal under the tested conditions. (LLM, conf=0.84)

The Clinical phenotype section and Table 1 report elevated IgA in both NCKAP1L-deficient patients, supporting the elevated-IgA portion of the claim. They do not report selective IgA deficiency or celiac disease; the section describes patient 2’s IgA elevation as massive, not mild. (LLM, conf=0.90)

The Results and discussion section on T-cell activation reports that, after strong stimulation, cytotoxic T cells from two patients had normal or even increased surface CD107a—not uniformly elevated levels. The section on impaired actin polymerization describes abnormal synapse and leading-edge formation, but does not report reduced cortical actin thickness; it says basal F-actin content in resting T cells did not differ from controls. Page numbers are unavailable in our copy. (LLM, conf=0.88)

The Clinical phenotype section (page unavailable) reports elevated IgE in patient 1, but normal IgE in patient 2. It does not establish that elevated IgE is frequent among HEM1-deficient patients or that it is especially associated with asthma or atopic symptoms. (LLM, conf=0.88)

The Results and discussion section reports higher basal degranulation in patient 1’s NK cells. It also says patient 2’s NK cells showed no abnormalities compared with the control, so the finding does not apply to both patients. (LLM, conf=0.88)

Table 1 in the Clinical phenotype section reports normal-range CD16/CD56 cell counts at the later measurement for both patients. It does not show decreased counts: at the earlier measurement, both patients’ counts were above their respective normal ranges. Thus, the paper supports 'normal' at one time point, but not 'normal or decreased across the cohort' without qualification. (LLM, conf=0.88)

The Clinical phenotype section describes two NCKAP1L-deficient patients but does not report food allergy, allergic rhinitis, asthma, or a prevalence of atopic disease. Searches for those conditions and for atopy in a HEM1-deficient cohort found no passage addressing the claim; the reported IgE level alone does not establish it. No page numbers were available in the indexed passages. (LLM, conf=0.73)

The Clinical phenotype section reports BCG lymphadenitis in one HEM1-deficient patient and recurrent otitis media and sinopulmonary infections in another. Searches for cellulitis, septic arthritis, and cholecystitis found no passage in our copy reporting any of those three conditions. (LLM, conf=0.75)