Molecular diagnosis of immunodeficiencies

• Published in: Biologicals Vol. 24; no. 3; p. 212
• Main Author: Elder, ME
• Format: Journal Article
• Language: English
• Published: 01.09.1996
• ISSN: 1045-1056

In the past few years, the mutations underlying several inherited immunodeficiencies have been identified. This has resulted in significant improvements in the diagnosis, the treatment, and in the genetic counselling of affected families. For example, a male infant with a history of recurrent bacterial infections and Pneumococcus carnii pneumonia, decreased serum immunoglobulin levels and normal to decreased B-cell numbers, would previously been considered to have an unusual form of X-linked hypogammaglobulinemia vs. combined B- and T-cell immunodeficiency. Currently, molecular probes and monoclonal antibodies are available that can distinguish between these diseases; in particular, the diagnosis of X-linked agammaglobulinaemia (Bruton's disease) vs. X-linked hyper IgM syndrome may be made. Severe combined immunodeficiency syndrome (SCID) is characterized by profound defects in T-cell and B-cell immunity. Approximately 40% of cases are inherited as X-linked traits and 25% of cases are due to adenosine deaminase deficiency; the remainder are thought to be due to sporadic or other inherited autosomal recessive mutations. Molecular techniques are now available to diagnose X-linked SCID and a rare, recessive form of SCID due to a defect in the signalling kinase ZAP-70. Chronic granulomatous disease (CGD) is characterized by defects in superoxide production by activated neutrophils. Approximately 60% of cases are X-linked defects. Mutations in at least four different genes encoding cytochrome b558 and additional oxidase components have been demonstrated in patients with CGD. Identification of gene defects in patients with CGD has resulted in significant improvement in genetic counselling of affected kindreds.