Genetic Studies of X-linked Lymphoproliferative Disease

This study will study the effects of the gene on the X chromosome that is associated with X-linked lymphoproliferative disease (XLPD)-an inherited disease affecting the immune system-on the function of the immune system. XLPD has been linked to an abnormality in a specific region of the X chromosome (one of 23 chromosome pairs that contain the genes that determine a person's hereditary makeup). The disease may develop after infection with the Epstein-Barr virus (EBV). EBV affects more than 95 percent of people in the United States. It usually does not cause any symptoms in children. In adolescents and adults, however, EBV can cause infectious mononucleosis and sometimes lymphoproliferative disease, such as XLPD. In these diseases lymph tissues, such as lymph nodes, may become enlarged and immune function (infection-fighting ability) impaired. This study will compare DNA from patients with XLPD with that of their unaffected relatives, of patients with other lymphoproliferative diseases and of normal controls. Patients of any age with XLPD, their unaffected relatives 18 years of age and older, and patients with other lymphoproliferative diseases may participate in this study. Blood samples will be collected from all participants to study the effects of the gene on the X chromosome that appears to be abnormal in XLPD on the function of the immune system. In a 6-week period, no more than 100 milliliters (about 7 tablespoons) of blood will be drawn from adults and no more than 1 ml (1/6 teaspoon) of blood per pound of body weight from children. Blood from patients with XLPD and their relatives will also be tested for HLA type (similar to blood type testing) and the ability of HLA-matched cells from patients and relatives to interact will be examined. ...

Sex

All

* INCLUSION CRITERIA:

Patients known to have XLPD and their relatives will be recruited from families who have enrolled in a national XLPD registry.

All racial and ethnic groups will be considered.

To be considered having XLPD, a patient must be a male who has had:

* severe infectious mononucleosis, or
* acquired hypogammaglobulinemia following infectious mononucleosis, or
* nonHodgkin's lymphoma, or
* hyper-IgM or an IgG subclass deficiency with evidence of linkage to the DXS42 locus

and

have no other known immunocompromising condition and belong to a family in which another related male has had one or more of the above listed phenotypes.

EXCLUSION CRITERIA:

Known HIV infection in any patient with XLPD or their relative (blood will not be tested for HIV), complicating medical or psychiatric conditions in unrelated controls.

• BACKGROUNDPurtilo DT, Cassel CK, Yang JP, Harper R. X-linked recessive progressive combined variable immunodeficiency (Duncan's disease). Lancet. 1975 Apr 26;1(7913):935-40. doi: 10.1016/s0140-6736(75)92004-8. PMID 48119
• BACKGROUNDSkare JC, Milunsky A, Byron KS, Sullivan JL. Mapping the X-linked lymphoproliferative syndrome. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2015-8. doi: 10.1073/pnas.84.7.2015. PMID 2882515
• BACKGROUNDCohen JI. Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency. Medicine (Baltimore). 1991 Mar;70(2):137-60. doi: 10.1097/00005792-199103000-00005. PMID 1848644