Related Experiment Videos
Lymphocytic vasculitis in X-linked lymphoproliferative disease.
1Departments of Medicine, Pathology & Laboratory Medicine and Pediatrics, University of British Columbia and British Columbia's Children's Hospital, British Columbia, Canada.
Blood
|January 3, 2001
Summary
Systemic vasculitis can be a rare symptom of X-linked lymphoproliferative disease (XLP), linked to Epstein-Barr virus (EBV) susceptibility. A novel mutation in the SLAM-associated protein (SAP) gene was identified in a patient with XLP-associated vasculitis.
Area of Science:
- Immunology
- Genetics
- Pathology
Background:
- X-linked lymphoproliferative disease (XLP) is a rare immune disorder characterized by susceptibility to Epstein-Barr virus (EBV).
- Mutations in the SLAM-associated protein (SAP) gene are the known molecular basis for XLP.
- Systemic vasculitis is an uncommon but severe manifestation of XLP.
Observation:
- A patient presenting with chronic systemic vasculitis met clinical criteria for XLP.
- The patient exhibited virus-associated hemophagocytic syndrome (VAHS), chorioretinitis, bronchiectasis, hypogammaglobulinemia, mononeuritis, and fatal respiratory failure.
- Autopsy revealed widespread small and medium vessel vasculitis affecting multiple organs, including the eyes, brain, heart, kidneys, testes, and pancreas.
Findings:
- Sequencing identified a novel point mutation in the SH2 domain of the patient's SAP gene.
- Immunohistochemistry showed vessel wall infiltrates composed primarily of CD8(+) T cells, suggesting a cytotoxic T-lymphocyte response.
- EBV DNA was detected in arterial wall tissue, indicating T cells targeted EBV antigens within endothelial cells.
Implications:
- Functional inactivation of SAP impairs the immune response to EBV, potentially leading to systemic vasculitis.
- This finding highlights the critical role of SAP in regulating immune responses to viral infections.
- Understanding this mechanism may inform diagnostic and therapeutic strategies for XLP and related vasculitic disorders.