CD40L deficiency
Definition: The X-linked hyper-IgM (XHIGM) syndrome is an uncommon primary immunodeficiency disease caused by mutations in the gene for CD40 ligand and characterized by normal or elevated serum IgM, reduced levels of IgG and IgA, and defective T-cell function.
The most prominent clinical infections were pneumonia (81% of patients), upper respiratory infections (49%) including sinusitis (43%) and recurrent otitis (43%), recurrent/protracted diarrhea (34%), central nervous system infections (14%), sepsis (13%), cellulitis (13%), hepatitis (9%), and osteomyelitis (1%).
Synopsis
significant IgG deficiency
+/- IgA deficiency
+/- elevated IgM levels
increased susceptibility to infection
- Pneumocystis carinii pneumonia
- infections caused by encapsulated bacteria
- opportunistic infections
- members of the herpes virus family (including cytomegalovirus)
- Cryptosporidium
- Cryptococcus
- Candida
- Histoplasma
- Bartonella
tonsillar hypertrophy
gingivitis
ulcerative stomatitis
hepatomegaly
chronic hepatitis
splenomegaly
diarrhea
proctitis
neutropenia, chronic or cyclic
anemia
hemolytic anemia
thrombocytopenia
immunodeficiency
dysgammaglobulinemia
primary dysfunction of B-lymphocyte isotype switching and memory B-cell generation
lymph nodes lacking germinal centers
normal or increased IgM
serum IgA, IgG, and IgE severely deficient
B-cell count normal
decreased T cell activation
recurrent bacterial infections with onset in the first or second year of life
Pneumocystis carinii infection (12 to 42%)
opportunistic infections
sclerosing cholangitis
- ascending Cryptosporidium sp. infection
tumors
- gallbladder tumors (12790080)
- hepatocellular carcinoma (14663287)
Etiology
caused by mutations in CD40L gene coding for the tumor necrosis factor ligand superfamily, member 5 gene (TNFSF5) or CD40-Ligand
References
Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, Stiehm ER, Conley ME. The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients.Medicine (Baltimore). 2003 Nov;82(6):373-84. PMID: 14663287