PROGRESSIVE DECREASE IN T CELL QUANTITY AND FUNCTION IN A PATIENT WITH IL-12 PATHWAY DEFECT

Abstract

Introduction T helper 1 (TH1) and IFN-g are key players in the cell-mediated immune response. Furthermore, IL-12 is an important cytokine that promotes TH1 cell differentiation and mediates its affects through signal transducer and activator of transcription 4 (STAT4). Mutations in the gene encoding the IL-12 receptor beta1 subunit have been identified in patients with disseminated Salmonella and nontuberculous mycobacterial (NTM) infections or disseminated Bacillus Calmette-Guerin (BCG) infection following vaccine administration. Case Description 5-month old female with history of recurrent salmonella enteritis and meningitis at 3 weeks and 3 months of age who presented to our Immunology clinic for an immune evaluation. Initial T cell lymphocyte subsets showed elevated CD3, CD4, CD8 and CD16/CD56 absolute values. Her mitogen culture proliferation assay was reported as low lymphocyte proliferation to ConA and PHA, however based on our assessment she had greater than tenfold response to stimulus and therefore normal function. The patient's lymphocyte subsets have been reassessed on a yearly basis and have showed progressive decline. This year, her CD4 and CD8 were 754 and 338 respectively. Mitogen proliferation culture re-assessment this year also showed significant decline in her T cell function and she was therefore started on Bactrim prophylaxis. Discussion Our patient showed progressive decline in her T cell subset values and decrease in overall function. Although classically MSMD (mendelian susceptibility to mycobacterial disease) patients showed increase susceptibility to disseminated BCG and Salmonella disease and is managed with interferon gamma and azithromycin prophylaxis, our patient now requires additional Bactrim prophylaxis. IL-12 Signaling Pathway