Lymphocytic vasculitis in X-linked lymphoproliferative disease

Systemic vasculitis is an uncommon manifestation of X-linked lymphoprolifer ative die ease (XLP), a disorder in which there is a selective immune defic iency to Epstein-Barr virus (EBV), The molecular basis for XLP has recently been ascribed to mutations within SLAM-associated protein (SAP), an SH2 do main-containing protein expressed primarily in T cells. The authors describ e a patient who died as a result of chronic systemic vasculitis and fulfill ed clinical criteria for the diagnosis of XLP. Sequencing of this patient's SAP gene uncovered a novel point mutation affecting the SH2 domain. The pa tient presented with virus-associated hemophagocytic syndrome (VAHS) and la ter had chorioretinitis, bronchiectasis, and hypogammaglobulinemia develop. He further developed mononeuritis and fatal respiratory failure. Evidence of widespread small and medium vessel vasculitis was noted at autopsy with involvement of retinal, cerebral, and coronary arteries as well as the segm ental vessels of the kidneys, testes, and pancreas. Immunohistochemical ana lysis using antibodies to CD20, CD45RO, and CD8 revealed that the vessel wa ll infiltrates consisted primarily of CD8(+) T cells, implying a cytotoxic T-lymphocyte response to antigen. EBV DNA was detected by polymerase chain reaction (PCR) in arterial wall tissue microdissected from infiltrated vess els further suggesting that the CD8(+) T cells were targeting EBV antigens within the endothelium, The authors pre pose that functional inactivation o f the SAP protein can impair the immunologic response to EBV, resulting in systemic vasculitis. (C) 2001 by The American Society of Hematology.