65 X-linked hyper IgM syndrome是由於下列何種分子之缺陷所引起？

CD28/B7 Fas/Fas ligand（FasL）

CD40/CD40 ligand（CD40L） Interferon-γ受體

answer CD40 ligand

Disease characteristics. X-linked hyper IgM syndrome (HIGM1), a disorder of abnormal T- and B-cell function, is characterized by low serum concentrations of IgG and IgA and normal or elevated serum concentrations of IgM. Mitogen proliferation may be normal, but NK- and T-cell cytotoxicity are frequently impaired. Antigen-specific responses may be decreased or absent. The range of clinical findings varies, even within the same family. Over 50% of males with HIGM1 develop symptoms by age one year, and more than 90% are symptomatic by age four years. HIGM1 usually presents in infancy with recurrent upper and lower respiratory tract bacterial infections, opportunistic infections, and recurrent or protracted diarrhea associated with failure to thrive. Neutropenia, thrombocytopenia, and anemia are common. Autoimmune and/or inflammatory disorders, such as sclerosing cholangitis, have been reported. Significant neurologic complications, often the result of a CNS infection, are seen in 10%-15% of affected males. Liver disease, including primary cirrhosis and carcinomas (bile duct carcinomas, hepatocellular carcinomas, adenocarcinomas of the liver and gall bladder), and tumors of the gastrointestinal tract (carcinoid of the pancreas, glucagonoma of the pancreas) are common life-threatening complications in adolescents and young adults with HIGM1. Affected males also have an increased risk of lymphoma, particularly Hodgkin's disease associated with Epstein-Barr virus (EBV) infection.

Diagnosis/testing. The diagnosis of HIGM1 is based on a combination of clinical findings, family history, absent or decreased expression of the CD40 ligand (CD40L) protein on flow cytometry following in vitro stimulation of white cells, and molecular genetic testing of CD40LG (previously known as TNFSF5 or CD154), the only gene known to be associated with HIGM1. Direct sequencing of the entire coding region and intron/exonboundaries detects mutations in approximately 99% of affected males.