XLP primarily affects boys, and is characterized by a life-long vulnerability to Epstein-Barr virus (EBV), a common type of herpes virus that usually does not cause symptoms other than a brief infection or mononucleosis. However, boys with XLP can have severe reactions to EBV infections.
XLP is associated with mutations in a gene called SH2D1A, which is located on the X chromosome and provides instructions for making SAP protein. These mutations can alter the structure and function of SAP or the amount of SAP produced. Lack of functional SAP causes defects in T- and B-cell interactions, which leads to abnormal immune responses to EBV.
Symptoms & Diagnosis
Boys with XLP are healthy until they are exposed to Epstein-Barr virus (EBV). Then, they can become seriously ill and experience swollen lymph nodes, an enlarged liver and spleen, hepatitis, and lymphoma. Some boys with XLP have developed lymphoma in the absence of EBV infection.
XLP may be suspected based on an overactive immune response to viral infection, such as development of severe mononucleosis in response to EBV infection. A blood test showing low antibody, or immunoglobulin, levels also may suggest XLP. Diagnosis of XLP requires a demonstrated lack of functional SAP or identification of a loss-of-function mutation in the SH2D1A gene.
Evidence suggests that rituximab, a drug that targets B cells, can be life-saving in boys with XLP and severe mononucleosis caused by EBV. Doctors may use immunoglobulin replacement therapy to treat the low level of immunoglobulin that occurs in some patients with XLP, but this will not necessarily protect a child against EBV infection. Bone marrow or umbilical cord blood transplantation, which re-set and replenish the immune system, can effectively cure XLP.