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Liver disease predicts mortality in patients with X-linked immunodeficiency with hyper-IgM but can be prevented by early hematopoietic stem cell transplantation

      X-linked immunodeficiency with hyper-IgM (XHIM) is a severe primary immunodeficiency disorder characterized by low levels of, or absence of IgG, IgA, and IgE, with normal to raised serum IgM concentrations.
      • Rosen F.S.
      • Kevy S.V.
      • Merler E.
      • Janeway C.A.
      • Gitlin D.
      Recurrent bacterial infections and dysgamma-globulinemia: deficiency of 7S gamma-globulins in the presence of elevated 19S gamma-globulins. Report of two cases.
      XHIM results from mutations in the CD40 ligand (CD40L) gene found on activated CD4 T cells
      • Etzioni A.
      • Ochs H.D.
      The hyper IgM syndrome–an evolving story.
      ; disruption of this gene results in aberrant interaction with CD40 on B-cell membranes, thus inhibiting B-cell proliferation and immunoglobulin class switching.
      • Hollenbaugh D.
      • Grosmaire L.S.
      • Kullas C.D.
      • Chalupny N.J.
      • Braesch-Andersen S.
      • Noelle R.J.
      • et al.
      The human T cell antigen gp39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co-stimulatory activity.
      CD40 is also found on other cells such as monocytes and endothelial and epithelial cells. Therefore, patients with XHIM have a combined immunodeficiency, resulting in recurrent bacterial and opportunistic infections. Sinopulmonary infections occur in approximately 80% of patients; gastrointestinal manifestations, including chronic diarrhea, affect approximately 50% of patients; and hepatic complications, which are principally biliary in nature, are reported to affect approximately 20% of patients with XHIM.
      • Winkelstein J.A.
      • Marino M.C.
      • Ochs H.
      • Fuleihan R.
      • Scholl P.R.
      • Geha R.
      • et al.
      The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients.
      • Levy J.
      • Espanol-Boren T.
      • Thomas C.
      • Fischer A.
      • Tovo P.
      • Bordigoni P.
      • et al.
      Clinical spectrum of X-linked hyper-IgM syndrome.
      The clinical presentation was broadly reflected in our cohort (see Table E1 in this article's Online Repository at www.jacionline.org).
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      References

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