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Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism
Abstract
Background Calprotectin (complex of S100A8 and S100A9) is the major calcium and zinc-binding protein of phagocytes. We report a new syndrome with recurrent infections, inflammation, and hyperzincaemia associated with excessively high plasma concentrations of calprotectin.Methods We measured calprotectin in plasma and protein fractions by ELISA assay and zinc by atomic absorption spectrometry. Plasma proteins were fractionated by size exclusion chromatography and electrophoresis. Mass spectra of purified proteins were determined by MALDI-TOFMS.Findings We assessed five patients, two of whom are related. All patients had much the same biochemical findings of hyperzincaemia (77-200 micromol/L, reference range 11-18 micromol/L) and raised plasma calprotectin concentrations (1.4-6.5 g/L, reference range <1 mg/L). All patients presented with recurrent infections, hepatosplenomegaly, anaemia, and evidence of systemic inflammation. Three patients had cutaneous inflammation and three presented in infancy with severe growth failure. Size exclusion chromatography showed that zinc and calprotectin were associated in a broad fraction with molecular weight range 100-300 kDa. Analysis by electrophoresis and mass spectrometry showed that the patients' protein contained normal S100A8 and S100A9 subunits.Interpretation Dysregulation of zinc metabolism associated with accumulation in plasma of S100A8 and S100A9 defines a new disease, which encompasses a pathological role for dysregulation of two members of the large S100 protein family.
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“however hypercalprotectinaemia, in which patients have excessive serum calprotectin, is associated with increased incidence of recurrent infections (Sampson et al., 2002).”
From The Impact of Dietary Transition Metals on Host-Bacterial Interactions (2018) · cites this paper as Sampson et al., 2002
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Whiteside, B. G., Titheradge, H. L., & Al‐Abadi, E. (2022) · Pediatric Rheumatology · doi:10.1186/s12969-022-00707-5 · Cited by 7
PAMI syndrome: A rare cause that can be easily misdiagnosed
Xu, X., Huang, H., Ding, F., Yang, Z., Wang, J., & Jin, Y. (2021) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.62367 · Cited by 6
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Mechanosensitive Genes in the Trabecular Meshwork at Homeostasis
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Disorders in the Transport of Copper, Iron, Magnesium, Manganese, Selenium and Zinc
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Self-citationChronic exposure to arsenite induces S100A8 and S100A9 expression in rat RBL-2H3 mast cells
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Disorders in the Transport of Copper, Iron, Magnesium, Manganese, Selenium and Zinc
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MBBS, F. B. J. B. (2021) · Wiley eBooks · doi:10.1002/9781119820307.ch3 · Cited by 4
Metadata
- Authors
- Sampson, B., Fagerhol, M. K., Sunderkötter, C., Golden, B. E., Richmond, P., Klein, N., Kovar, I. Z., Beattie, J. H., Wolska-Kusnierz, B., Saito, Y., & Roth, J.
- Affiliations
- Charing Cross Hospital (GB)
- Oslo University Hospital (NO)
- University of Münster (DE)
- University of Aberdeen (GB)
- Chelsea and Westminster Hospital (GB)
- Tokyo Women's Medical University (JP)
- Corresponding author
- Sampson, Barry
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 360
- Issue
- 9347
- Pages
- 1742-1745
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2145976476
- Cited by
- 122
- References
- 33
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 7 · 2015: 5 · 2014: 4 · 2013: 6 · 2012: 12
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- calprotectin, S100A8, S100A9, recurrent infections, systemic inflammation, hepatosplenomegaly, anemia, skin inflammation, growth failure, plasma protein fractionation, S-100 protein
- MeSH terms
- Adolescent, Adult, Child, Female, Humans, Male, Syndrome, Zinc, Leukocyte L1 Antigen Complex
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