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(American Journal of Pathology. 1999;155:915-925.)
© 1999 American Society for Investigative Pathology

Regular Articles

Involvement of Soluble CD95 in Churg-Strauss Syndrome

Markus Müschen^*§, Ulrich Warskulat^*, Andreas Perniok, Jos Even^§, Cordula Moers, Berrin Kismet^*, Nazan Temizkan^*, Dietmar Simon, Matthias Schneider and Dieter Häussinger^*

From the Departments of Gastroenterology, Hepatology and Infectiology,^*
Rheumatology,
and General Surgery,
University of Düsseldorf, Düsseldorf, Germany; and the Department of Immunology,^§
Unité de Biologie Moléculaire du Gène, Institut Pasteur, Paris, France

Deficiency of CD95 (Apo-1/Fas)-mediated apoptosis has recently been found in some autoimmune lymphoproliferative disorders due to inherited mutations of the CD95 gene. In this study, impairment of CD95 ligand-mediated killing of lymphocytes and eosinophils in Churg-Strauss Syndrome (CSS), which was a result of variation of CD95 receptor isoform expression, is demonstrated. Compared to those from healthy individuals, peripheral blood lymphocytes from eight CSS patients exhibit a switch from the membrane-bound CD95 receptor expression to its soluble splice variant, which protects from CD95L-mediated apoptosis. In five out of seven CSS patients recurrent oligoclonal T cell expansions were found, all using a Vß-gene from the Vß21 family associated with similar CDR3 motifs, indicating the predominance of T cell clones of a similar specificity in the CSS patients. In two of them, the effect of immunosuppressive therapy was studied. In both cases aberrant overexpression of the soluble CD95 receptor isoform and deviations from normal TCR Vß-gene usage normalized in parallel with the clinical improvement. Furthermore, soluble CD95 was identified as a survival factor for eosinophils rescuing eosinophils from apoptosis in the absence of growth factors in vitro. Given the role of eosinophils as effector cells in CSS, these findings suggest that soluble CD95 may be mechanistically involved in the disease.

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