Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism

B. Sampson, M. K. Fagerhol, C. Sunderkotter, Barbara Elaine Golden, P. Richmond, N. Klein, I. Z. Kovar, J. H. Beattie, B. Wolska-Kusnierz, Y. Saito, J. Roth

    Research output: Contribution to journalArticle

    92 Citations (Scopus)

    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 mumol/L, reference range 11-18 mumol/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.

    Original languageEnglish
    Pages (from-to)1742-1745
    Number of pages3
    JournalThe Lancet
    Volume360
    Issue number9347
    DOIs
    Publication statusPublished - 2002

    Keywords

    • CALCIUM-BINDING PROTEINS
    • MYELOID DIFFERENTIATION
    • IMMUNE-RESPONSE
    • S100 PROTEIN
    • CALPROTECTIN
    • CELLS
    • PLASMA
    • FAMILY
    • MRP14
    • NEUTROPHILS

    Cite this

    Sampson, B., Fagerhol, M. K., Sunderkotter, C., Golden, B. E., Richmond, P., Klein, N., ... Roth, J. (2002). Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism. The Lancet, 360(9347), 1742-1745. https://doi.org/10.1016/S0140-6736(02)11683-7

    Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism. / Sampson, B.; Fagerhol, M. K.; Sunderkotter, C.; Golden, Barbara Elaine; Richmond, P.; Klein, N.; Kovar, I. Z.; Beattie, J. H.; Wolska-Kusnierz, B.; Saito, Y.; Roth, J.

    In: The Lancet, Vol. 360, No. 9347, 2002, p. 1742-1745.

    Research output: Contribution to journalArticle

    Sampson, B, Fagerhol, MK, Sunderkotter, C, Golden, BE, Richmond, P, Klein, N, Kovar, IZ, Beattie, JH, Wolska-Kusnierz, B, Saito, Y & Roth, J 2002, 'Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism', The Lancet, vol. 360, no. 9347, pp. 1742-1745. https://doi.org/10.1016/S0140-6736(02)11683-7
    Sampson B, Fagerhol MK, Sunderkotter C, Golden BE, Richmond P, Klein N et al. Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism. The Lancet. 2002;360(9347):1742-1745. https://doi.org/10.1016/S0140-6736(02)11683-7
    Sampson, B. ; Fagerhol, M. K. ; Sunderkotter, C. ; Golden, Barbara Elaine ; Richmond, P. ; Klein, N. ; Kovar, I. Z. ; Beattie, J. H. ; Wolska-Kusnierz, B. ; Saito, Y. ; Roth, J. / Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism. In: The Lancet. 2002 ; Vol. 360, No. 9347. pp. 1742-1745.
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    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 mumol/L, reference range 11-18 mumol/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.",
    keywords = "CALCIUM-BINDING PROTEINS, MYELOID DIFFERENTIATION, IMMUNE-RESPONSE, S100 PROTEIN, CALPROTECTIN, CELLS, PLASMA, FAMILY, MRP14, NEUTROPHILS",
    author = "B. Sampson and Fagerhol, {M. K.} and C. Sunderkotter and Golden, {Barbara Elaine} and P. Richmond and N. Klein and Kovar, {I. Z.} and Beattie, {J. H.} and B. Wolska-Kusnierz and Y. Saito and J. Roth",
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    language = "English",
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    TY - JOUR

    T1 - Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism

    AU - Sampson, B.

    AU - Fagerhol, M. K.

    AU - Sunderkotter, C.

    AU - Golden, Barbara Elaine

    AU - Richmond, P.

    AU - Klein, N.

    AU - Kovar, I. Z.

    AU - Beattie, J. H.

    AU - Wolska-Kusnierz, B.

    AU - Saito, Y.

    AU - Roth, J.

    PY - 2002

    Y1 - 2002

    N2 - 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 mumol/L, reference range 11-18 mumol/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.

    AB - 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 mumol/L, reference range 11-18 mumol/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.

    KW - CALCIUM-BINDING PROTEINS

    KW - MYELOID DIFFERENTIATION

    KW - IMMUNE-RESPONSE

    KW - S100 PROTEIN

    KW - CALPROTECTIN

    KW - CELLS

    KW - PLASMA

    KW - FAMILY

    KW - MRP14

    KW - NEUTROPHILS

    U2 - 10.1016/S0140-6736(02)11683-7

    DO - 10.1016/S0140-6736(02)11683-7

    M3 - Article

    VL - 360

    SP - 1742

    EP - 1745

    JO - The Lancet

    JF - The Lancet

    SN - 0140-6736

    IS - 9347

    ER -