Abstract 58
Allergy, Immunology, and Rheumatology Poster Symposium, Sunday, 5/2
X-linked lymphoproliferative disease (XLP) is a rare genetic disorder that is characterized by an abnormal immune response to Epstein-Barr virus (EBV) infection. One of the following clinical conditions may ensue after infection with EBV: fatal mononucleosis, hypogammaglobulinemia, aplastic anemia and or lymphoma. The gene defect has been localized to Xq25 and the diagnosis of the defect can been determined by restriction fragment length polymorphism (RFLP) linkage analysis. An extensive genetic analysis on three generations of a kindred of a 15 year male clinically diagnosed with XLP and hypogammaglobulinemia was performed by our Allergy-Immunology division. Two males members died of what was probably fatal mononucleosis. Among the surviving family members, immunoglobulin levels, EBV serology and RFLP analysis was carried using previously identified DNA probes that are linked to the XLP gene, including DXS42, DXS37, DXS10, DXS11, DXS424, and HPRT. Using these probes we were able to identify two young asymptomatic male siblings with EBV positive serology that carry the genetic defect as well as seven female carriers. EBV IgG titers were elevated (1:640 and 1:160) on both siblings and undetectable EBV IgM titers. Total immunoglobulin concentration in the two male siblings were normal except for mild IgG 2 deficiency. None of these siblings manifested with a EBV like illness or have received intravenous immunoglobulin. It is possible for male family members in a kindred diagnosed with the XLP gene defect to remain asymptomatic and not manifest with a progressive fatal disease. The recent publication of the SLAM associated protein (SAP) gene sequence will allow the identification of the mutation associated with the different phenotypes in this kindred.
