Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations

作者：Bradford Kathryn L; Moretti Federico A; Carbonaro Sarracino Denise A; Gaspar Hubert B; Kohn Donald B

来源：Journal of Clinical Immunology, 2017, 37(7): 626-637.

DOI：10.1007/s10875-017-0433-3

• Adenosine Deaminase
• Purine metabolism
• SCID
• Lymphopenia
• Gene therapy
• Clinical trials

Deficiency of adenosine deaminase (ADA, EC3.5.4.4), a housekeeping enzyme of purine metabolism encoded by the Ada gene, is a cause of human severe combined immune deficiency (SCID). Numerous deleterious mutations occurring in the ADA gene have been found in patients with profound lymphopenia (T- B- NK-), thus underscoring the importance of functional purine metabolism for the development of the immune defense. While untreated ADA SCID is a fatal disorder, there are multiple life-saving therapeutic modalities to restore ADA activity and reconstitute protective immunity, including enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) with autologous gene-corrected hematopoietic stem cells (HSC). We review the pathogenic mechanisms and clinical manifestations of ADA SCID.

• 出版日期2017-10