TY - JOUR
T1 - The hyper IgM syndrome.
AU - Fuleihan, R. L.
N1 - Funding Information:
Identification of the defect in CD40 ligand in X-HIM will allow us to develop a better description of the clinical manifestations of the disease. Registries for X-HIM and other primary immune deficiency diseases have been established in Europe by the European Society for Immunodeficiencies [24], and by the Immune Deficiency Foundation and the National Institute of Allergy and Infectious Diseases in the US. A report by the European group describes the clinical manifestations and immune function in 56 patients who met the criteria for X-HIM [2]. Infection was the most common clinical manifestation, with respiratory tract infections the most frequent among them. Gastrointestinal disease was the second most common, occurring in over half the patients. This category included diarrhea, oral ulcers associated with neutropenia, sclerosing cholangitis associated with cryptosporidosis, hepatitis, and liver cirrhosis with hepatic failure or severe cholestasis requiring liver transplantation. Hematologic abnormalities included neutropenia and anemia. Thirteen of the 56 X-HIM patients in this report [2] had died between 9 months and 23 years of age. The causes of death included infection, liver failure, and cancer. The oldest living patient was 23 years old. These findings emphasize that X-HIM is a severe immune deficiency with significant morbidity and mortality.
PY - 2001/9
Y1 - 2001/9
N2 - The hyper IgM syndrome is a rare, inherited immune deficiency disorder resulting from defects in the CD40 ligand/CD40-signaling pathway. X-linked hyper IgM is caused by defects in the CD40 ligand gene, while autosomal recessive hyper IgM is caused by defects in the CD40-activated RNA-editing enzyme, activation-induced cytidine deaminase, which is required for immunoglobulin isotype switching and somatic hypermutation in B cells. The loss of interaction between CD40 and its ligand in X-linked hyper IgM results in an impairment of T cell function, of B cell differentiation, and of monocyte function, while only B cell differentiation appears to be affected in autosomal recessive hyper IgM. With genetic defects in the hyper IgM syndrome identified, it is possible to diagnose patients definitely, to perform genetic screening, and to delineate the clinical manifestations of this syndrome. Further research may lead to novel and definitive therapeutic options for patients with hyper IgM syndrome.
AB - The hyper IgM syndrome is a rare, inherited immune deficiency disorder resulting from defects in the CD40 ligand/CD40-signaling pathway. X-linked hyper IgM is caused by defects in the CD40 ligand gene, while autosomal recessive hyper IgM is caused by defects in the CD40-activated RNA-editing enzyme, activation-induced cytidine deaminase, which is required for immunoglobulin isotype switching and somatic hypermutation in B cells. The loss of interaction between CD40 and its ligand in X-linked hyper IgM results in an impairment of T cell function, of B cell differentiation, and of monocyte function, while only B cell differentiation appears to be affected in autosomal recessive hyper IgM. With genetic defects in the hyper IgM syndrome identified, it is possible to diagnose patients definitely, to perform genetic screening, and to delineate the clinical manifestations of this syndrome. Further research may lead to novel and definitive therapeutic options for patients with hyper IgM syndrome.
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U2 - 10.1007/s11882-001-0030-6
DO - 10.1007/s11882-001-0030-6
M3 - Review article
C2 - 11892071
AN - SCOPUS:0035468185
SN - 1529-7322
VL - 1
SP - 445
EP - 450
JO - Current allergy and asthma reports
JF - Current allergy and asthma reports
IS - 5
ER -