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Increases in circulating and lymphoid tissue interleukin-10 in autoimmune lymphoproliferative syndrome are associated with disease expression

  1. Author:
    Lopatin, U.
    Yao, X.
    Williams, R. K.
    Bleesing, J. J.
    Dale, J. K.
    Wong, D.
    Teruya-Feldstein, J.
    Fritz, S.
    Morrow, M. R.
    Fuss, I.
    Sneller, M. C.
    Raffeld, M.
    Fleisher, T. A.
    Puck, J. M.
    Strober, W.
    Jaffe, E. S.
    Straus, S. E.

  2. Author Address

    Laboratory of Clinical Investigation, Clinical Research Training Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
    1. Year: 2001
  2. Journal: Blood
    1. 97
    2. 10
    3. Pages: 3161-3170
  4. Type of Article: Article
  1. Abstract:

    Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which genetic defects in proteins that mediate lymphocyte apoptosis, most often Fas, are associated with enlargement of lymph nodes and the spleen and a variety of autoimmune manifestations. Some patients with ALPS have relatives with these same apoptotic defects, however, who are clinically well. This study showed that the circulating levels of interleukin 10 (IL-10) were significantly higher (P <.001) in 21 patients with ALPS than in healthy controls. Moreover, the peripheral blood mononuclear cells (PBMCs) and lymphoid tissues of these patients with ALPS contained significantly higher levels of IL-10 messenger RNA (mRNA; P <.001 and P <.01, respectively). By fractionating PBMC populations, disproportionately high concentrations of IL-10 mRNA were found in the CD4(-)CD8(-) T-cell population, expansion of which is virtually pathognomonic for ALPS. Immunohistochemical staining showed intense IL-10 protein signals in lymph node regions known to contain CD4(-)CD8(-) T cells. Nonetheless, in vitro studies showed no influence of IL-10 on the survival of CD4(-)CD8(-) T cells. Overexpression of IL-10 in patients with inherited apoptotic defects is strongly associated with the overt manifestations of ALPS.

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