Immunodeficiency and Defective Purine Catabolism

Persons with severe combined immune deficiency (SCID) are totally unable to mount an immune response to antigens. Both the B and T lymphocytes are affected. The disease arises from an inherited lack of a degradative enzyme, adenosine deaminase (ADA). The reaction shown here illustrates the pathways affected. Lack of ADA allows deoxyadenosine triphophosphate (dATP) to accumulate from the degradation of DNA. High dATP levels inhibit production of the other dNTPs needed for DNA replication because of their allosteric effects on the enzyme ribonucleotide reductase.

White blood cells are the most affected by lack of ADA. White blood cells must proliferate for an immune response to occur, and proliferations requires ample synthesis of DNA and its precursors. Thus, DNA replication is inhibited and white blood cells are unable to proliferate, a necessary step for antibody production.

See also: Purine Degradation, The Immune Response (from Chapter 7), Antibody Structure (from Chapter 7), Generation of Antibody Diversity (from Chapter 7)