Alterations of the X-linked lymphoproliferative disease geneSH2D1A in common variable immunodeficiency syndrome

作者：Massimo Morra, Olin Silander, Silvia Calpe, Michelle J. Choi, Hans C. Oettgen, Laurie A. Myers, Amos Etzioni, Rebecca H. Buckley, Cox Terhorst · 发表于：Blood · 年份：2001 · DOI：10.1182/blood.v98.5.1321 · 被引用次数：118 · 研究领域：Immunodeficiency and Autoimmune Disorders、Immune Cell Function and Interaction、Respiratory viral infections research

X-linked lymphoproliferative (XLP) disease is a primary immunodeficiency caused by a defect in the SH2D1A gene. At least 3 major manifestations characterize its clinical presentation: fatal infectious mononucleosis (FIM), lymphomas, and immunoglobulin deficiencies. Common variable immunodeficiency (CVID) is a syndrome characterized by immunoglobulin deficiency leading to susceptibility to infection. In some patients with CVID, a defective btk or CD40-L gene has been found, but most often there is no clearly identified etiology. Here, 2 unrelated families in whom male members were affected by CVID were examined for a defect in the XLP gene. In one family previously reported in the literature as having progressive immunoglobulin deficiencies, 3 brothers were examined for recurrent respiratory infections, whereas female family members showed only elevated serum immunoglobulin A levels. A grandson of one of the brothers died of a severe Aspergillus infection secondary to progressive immunoglobulin deficiency, FIM, aplastic anemia, and B-cell lymphoma. In the second family, 2 brothers had B lymphocytopenia and immunoglobulin deficiencies. X-linked agammaglobulinemia syndrome was excluded genetically, and they were classified as having CVID. The occurrence of FIM in a male cousin of the brothers led to the XLP diagnosis. Because the SH2D1A gene was found altered in both families, these findings indicate that XLP must be considered when more than one male patient with CVID is encoun...