National Institute of Arthritis and Musculoskeletal and Skin Diseases

September 6, 1995

Contact: Elia Ben-Arii 
Office of Scientific and 
Health Communications 
(301) 496-8188

Researchers have discovered a new cause of severe combined immune deficiency (SCID) in infants. Children with SCID are born with extensive immune system defects that make them highly susceptible to infections. In the September 7 issue of the journal Nature, investigators from Italy and their colleagues at the National Institutes of Health (NIH) in Bethesda, Md., describe two patients with autosomal recessive SCID who have mutations in the gene encoding a protein called Jak-3. These findings raise the possibility of designing gene therapy for this form of SCID. In the long term these findings might lead to development of a new class of drugs to treat autoimmune diseases such as lupus and rheumatoid arthritis by selectively turning off the immune response.

Jak-3 is an enzyme found inside some cells, including white blood cells. It is part of a complex biochemical bucket brigade that transmits growth-stimulating signals received from certain cells across the cell membrane and into the nucleus of other cells. These growth signals start out in the form of cytokines, factors secreted by white blood cells, or lymphocytes, that cause other white blood cells to mature, grow, and develop specialized functions. Previous research at NIH showed that another form of SCID, X-linked SCID, is caused by mutations in certain cytokine receptor molecules, which are the first step in the bucket brigade that responds to cytokine stimulation. Dr. John O'Shea and his colleagues first cloned human Jak-3, the next step in this chain of events, and predicted that other forms of SCID might be caused by mutations in this gene. Now, Dr. Anna Villa and colleagues in Italy have identified two patients with autosomal recessive SCID who have mutations in the Jak-3 gene. NIH researchers led by O'Shea have shown that these mutations result in a marked reduction in the amount of Jak-3 protein in cells from these patients.

SCID refers to a group of inherited disorders that includes the disease from which the "bubble boy" suffered (X-linked SCID). These disorders are the most serious of the primary immune deficiency disorders, in which inborn defects of the immune system lead to often chronic, frequent, and sometimes severe bacterial, viral and fungal infections. The current treatment of choice for infants with SCID is bone marrow transplantation, which is successful in more than half of all cases. Without treatment, infants with SCID rarely survive beyond their first year.

Last Reviewed: