The X-linked lymphoproliferative syndrome is a result of a defect in the T-cells and natural killer cells and is characterized by an abnormal sensitivity to Epstein-Barr virus infections. This can lead to liver failure, immunodeficiency, lymphoma, fatal lymphoproliferative diseases or bone marrow aplasia.
(See also Overview of immune deficiency disorders, and approach to the patient with an immunodeficiency disorder.)
The X-linked lymphoproliferative syndrome is a result of a defect in the T-cells and natural killer cells and is characterized by an abnormal sensitivity to Epstein-Barr virus infections. This can lead to liver failure, immunodeficiency, lymphoma, fatal lymphoproliferative diseases or bone marrow aplasia. (See also Overview of immune deficiency disorders, and approach to the patient with an immunodeficiency disorder.) The X-linked lymphoproliferative syndrome (XLP) is a primary immunodeficiency disease, belong to the cellular immunity deficiencies. It is caused by mutations in genes on the X chromosome. It is a recessive disorder and therefore manifests itself only in men. Type 1 of the XLP is the most common type (about 60% of all cases). It is caused by a mutation of the gene encoding the signaling lymphocyte activation molecule (SLAM) -associated protein (SAP, also called SH2 domain protein 1A [SH2D1A] or DSHP hereinafter) encoded. Without SAP, the lymphocytes proliferate in an uncontrolled reaction to an Epstein-Barr virus (EBV) infection, while natural killer (NK) cells do not work. Type 2 of the XML type 1 is clinically similar and results in a predisposition to the hemophagocytic lymphohistiocytosis (HLH), a rare disease, immunodeficiency disorders in infants and young children caused. XLP2 is caused by mutations of the gene encoding X-linked inhibitor of apoptosis protein (XIAP) encoded. Symptoms and complaints The syndrome usually remains asymptomatic until the occurrence of an EBV infection. Then most patients develop very severe or fatal infectious mononucleosis with hepatic impairment (caused by cytotoxic T cells that respond to EBV-infected B or other tissue cells). Patients who survive the initial infection, develop B-cell lymphoma, aplastic anemia, hypogammaglobulinemia (similar to variable immunodeficiency), splenomegaly or a combination thereof. Diagnostic genetic tests The diagnosis of XLP should be considered in young men who have a severe EBV infection, HLH, a suggestive family history or other common manifestations. Genetic tests represent the gold standard to confirm the diagnosis (before and after EBV infection and the development of symptoms) and the carrier state. However, can take weeks to complete the full implementation of genetic testing so that other tests are used when the diagnosis already must be made before (z. B. flow cytometry to assess the SH2D1A protein expression). Suspicious findings include Reduced antibody responses to antigens (especially EBV nuclear antigen) Impaired T cell proliferative response to mitogens Decreased NK-cell function An inverted CD4: CD8 ratio These findings before and typically after EBV infection. A bone marrow biopsy can help in confirming HLH. Laboratory tests and imaging procedures are performed annually in survivors, to check for lymphoma and anemia. Genetic testing in relatives are performed when a case or carrier has been identified in a family. Prenatal screening is recommended for persons who are causing a mutation that XLP has been identified in the family. Therapy hematopoietic stem cell transplantation Approximately 75% of patients do not reach the age of 10, and all patients die before reaching the age of 40, unless hematopoietic stem cell transplantation is performed. About 80% of patients who receive a transplant survive. A transplant is curative, when taken before the EBV infection or other disorders have become irreversible. Rituximab can help prevent severe EBV infection before transplantation.