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.
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.
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.
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
Correspondence to Christoph Klein, MD, PhD, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Lindwurmstr. 4, D-80337 Munich, Germany. Tel: +49 89 4400 57701; fax: +49 89 4400 57702; e-mail: firstname.lastname@example.org