title: Human IL-21 and IL-21R deficiencies: two novel entities of primary immunodeficiency.
abstract: OBJECTIVE
  This review highlights the recent identification of human interleukin-21 (IL-21) and interleukin-21 receptor (IL-21R) deficiencies as novel entities of primary immunodeficiency.
  
  
  RESULTS
  We recently described the first patients with IL-21R deficiency who had cryptosporidial infections associated with chronic cholangitis and liver disease. All IL-21R-deficient patients suffered from recurrent respiratory tract infections. Immunological work-up revealed impaired B cell proliferation and immunoglobulin class-switch, reduced T cell effector functions, and variable natural killer cell dysfunctions. Recently, these findings have been extended by the discovery of one patient with a mutation in the IL21 gene. This patient predominantly manifested with very early onset inflammatory bowel disease and recurrent respiratory infections. Laboratory examination showed reduced circulating B cells and impaired B cell class-switch.
  
  
  CONCLUSIONS
  Human IL-21 and IL-21R deficiencies cause severe, primary immunodeficiency reminiscent of common variable immunodeficiency. Early diagnosis is critical to prevent life-threatening complications, such as secondary liver failure. In view of the critical role of IL-21 in controlling immune homeostasis, early hematopoietic stem cell transplantation might be considered as therapeutic intervention in affected children.
authors.affiliation: aDepartment of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich bInstitute of Immunology, Hannover Medical School, Hannover, Germany cLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kotlarz
authors.forename: Natalia
authors.initials: N
authors.lastname: Ziętara
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Milner
authors.forename: Christoph
authors.initials: C
authors.lastname: Klein
mesh_terms: D002648:Child; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007378:Interleukins / Q000172:deficiency* / Q000235:genetics; D053655:Receptors, Interleukin-21 / Q000172:deficiency* / Q000235:genetics; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21