XLP is expanded as X-linked lymphoproliferative syndrome which is a very rare immunodeficiency disease that leads to fatal Epstein-Barr virus or EBV infection. Epstein Barr virus infection leads to infectious mononucleosis especially in childhood which may cause subsequent hypogammaglobulinemia, and predisposes a patient to markedly increased risk of lymphoma or other lymphoproliferative diseases.

 

In this disorder there is a mutation on the X chromosome which is associated with a T and NK cell lymphoproliferative disorder. The mutation affects the long arm of the chromosome located at position 25 which is refers as Xq25. Due to mutation at this position a gene known as SH2D1A gene is deleted. This gene codes for an SH2 domain on a signal transducing protein called SLAM-associated protein or SAP. The SH2 domain is a src-homology 2 domain, it is a three-dimensional domain structure formed by 100 amino acid residues. These domains are constituents of signaling proteins because they permit specific, non-covalent bonding to proteins that contain phosphotyrosines. The amino acid residues adjacent to the phosphotyrosines on the target protein are what determine the unique binding specificity. The SAP protein signals which lead to activation of T and NK cells. It functions as an intracellular adapter and transduces T and NK cell activation. SAP protein expresses in the cytoplasm of T and NK cells, where it binds to the cytoplasmic domain of the surface receptor known as Signaling Lymphocyte Activation Molecule or SLAM. This binding leads to the initiation of a signal transduction pathway, which results in the modulation of Interferon. A deletion in the SH2D1A gene makes SH2 domain non-functional on the SAP protein, thus it is unable to bind to the SLAM molecule, leading to a lack of modulation of IFN, causing uncontrolled cell proliferation. Boys with X-linked lymphoproliferative disorder show overwhelming T-cell mediated response to the Epstein - Barr virus, which may leads to death from bone marrow failure, or the condition, can pass into irreversible hepatitis, and malignant Lymphoma. The connection between EBV and X-linked lymphoproliferative disorder is not fully understood and established yet. The patients usually have insufficient numbers of CD27 memory B cells.

Signs and Symptoms

• Fever
• Pallor
• Pharyngitis
• Hepatosplenomegaly
• Lymphadenopathy
• Jaundice
• Ecchymosis