IL21R immunodeficiency is an autosomal recessive primary immunodeficiency characterized by B- and T-cell defects and variable dysfunction of NK cells. Patients tend to have normal numbers of lymphocytes, but show defective class-switched B cells, low IgG, defective antibody ... IL21R immunodeficiency is an autosomal recessive primary immunodeficiency characterized by B- and T-cell defects and variable dysfunction of NK cells. Patients tend to have normal numbers of lymphocytes, but show defective class-switched B cells, low IgG, defective antibody response, and defective T-cell responses to certain antigens (summary by Kotlarz et al., 2013).
Kotlarz et al. (2013) reported 2 sibs, born of consanguineous Lebanese parents, with immunodeficiency. The patients had early onset of recurrent infections, as well as chronic cholangitis and biliary and hepatic cirrhosis associated with Cryptosporidium infection. One patient ... Kotlarz et al. (2013) reported 2 sibs, born of consanguineous Lebanese parents, with immunodeficiency. The patients had early onset of recurrent infections, as well as chronic cholangitis and biliary and hepatic cirrhosis associated with Cryptosporidium infection. One patient died after complications of liver transplantation and the other patient died after complications from hematopoietic stem cell transplantation. Laboratory studies showed relatively normal numbers of lymphocytes, but decreased numbers of class-switched B cells, defective antibody responses, reduced proliferative capacity of B cells, decreased T-cell proliferation in responses to certain antigens, and decreased NK cell-mediated lysis. Serum IgE was increased and IgG was decreased. Patient cells also showed decreased secretion of certain cytokines, including IL17F (606496) and IL22 (605330), which may have explained the increased susceptibility to Cryptosporidium infection. Two sibs from a second family had recurrent respiratory and gastrointestinal infections and liver disease due to Cryptosporidium infection. Laboratory studies showed normal lymphocyte numbers, but there were functional abnormalities, including decreased IgG, decreased antibody and T-cell responses to activation, increased IgE, and decreased IL21-dependent class-switching. One patient had impaired NK cell-mediated cytotoxicity.
In 4 patients from 2 unrelated consanguineous families with ILR21 immunodeficiency, Kotlarz et al. (2013) identified 2 different homozygous loss-of-function mutations in the IL21R gene (605383.0002 and 605383.0003, respectively). Patient cells showed impaired IL21R-mediated signaling and severe abrogation ... In 4 patients from 2 unrelated consanguineous families with ILR21 immunodeficiency, Kotlarz et al. (2013) identified 2 different homozygous loss-of-function mutations in the IL21R gene (605383.0002 and 605383.0003, respectively). Patient cells showed impaired IL21R-mediated signaling and severe abrogation of phosphorylation of downstream mediators, including STAT proteins (see, e.g., STAT3, 102582).