Presenting Author:

Aaruni Khanolkar, M.B.B.S.

Principal Investigator:

Aaruni Khanolkar, MBB.S.

Department:

Pathology

Keywords:

IFNgR1; Mycobacterium; pSTAT5; pSTAT1; IFNg; CD4 T cells; CD8 T cells; IL-2; phosflow-signaling.

Location:

Ryan Family Atrium, Robert H. Lurie Medical Research Center

C79 - Clinical

CD4-T cell-restricted IL-2 signaling-defect in a patient with a novel-IFNGR1-deficiency

We identified a patient who is a compound heterozygote for mutations in the interferon-gamma receptor-1 gene [a maternally-derived frame-shift mutation in exon 4 and a paternally-derived premature stop-codon in exon 5]. Clinically, the patient has experienced pulmonary infections with mycobacterium fortuitum, mycobacterium-avium complex that were controlled with medications targeting rapid and slow-growing mycobacteria. In addition the patient developed chicken-pox following Varivax administration and also experienced a prolonged episode of severe eczema starting right after birth that was controlled at 6 months of age with topical medication. The patient who is now ~ 4. 5 years old continues to experience intermittent episodes of HSV-induced gingivo-stomatitis but is clinically-stable and awaiting a peripheral blood stem cell transplant. Immunologically the patient had slightly depressed CD8 T cell and NK cell counts at initial analysis and mildly elevated frequencies of both isotype-switched and unswitched circulating B cells and normal mitogen-induced lymphocyte proliferation. We also observed a loss of IFNgR1 expression on the patient's lymphocytes and complete abrogation of STAT1 phosphorylation following treatment with recombinant human IFNg. In depth analysis of immune function additionally identified an IL-2 associated signaling deficiency that was restricted primarily to the circulating CD4 T cell subset.