X-Linked Lymphoproliferative Disease (XLP)

XLP primarily affects boys and is characterized by a life-long vulnerability to Epstein-Barr virus (EBV), a common type of herpesvirus that usually does not cause symptoms other than a brief infection or mononucleosis. Boys with XLP, however, can have severe reactions to EBV infections.

Why Is the Study of X-Linked Lymphoproliferative Disease (XLP) a Priority for NIAID?

XLP is a rare genetic disease that may be chronic, debilitating, and costly. By learning more about this disease and its effects on the body, scientists gain a greater understanding of immune function that can inform multiple areas of research.

How Is NIAID Addressing This Critical Topic?

NIAID-supported investigators examine the causes and complications of rare diseases like XLP to improve the lives of patients and families. NIAID aims to improve diagnosis, develop prevention strategies, and explore new treatments to improve health and expand scientific knowledge through research.

XLP is a primary immune deficiency disease (PIDD). For more information on PIDD research and patient care at NIAID, visit the NIAID PIDD site.

To learn about risk factors for XLA and current management and treatment strategies visit the National Library of Medicine, Genetics Home Reference X-linked lymphoproliferative disease site.

Epstein-Barr virus (green dots) is shown inside B cells (blue circles) but not T cells (red circles).
Credit: NIAID
Epstein-Barr virus (green dots) is shown inside B cells (blue circles) but not T cells (red circles).
Causes

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.

Treatment

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.

What's New: 

Content last reviewed on June 27, 2016