Abstract
We identified PRKDC mutations in both patients. These patients exhibited a defect in DNA DSB repair and V(D)J recombination. Circulating T cells had a skewed cytokine response typical of Th1 and Th2 profiles. Moreover, mutated DNA-PKcs failed to promote AIRE-dependent transcription of peripheral tissue antigens in vitro .T he latter defect correlated in vivo, with the production of antiCalcium Sensing Receptor (anti-CaSR) autoantibodies, which are usually found in AIRE-deficient patients. Conclusion Deficiency of DNA-PKcs, a key AIRE partner, can present as an inflammatory disease with organ-specific autoantibodies and these findings highlight the essential role of DNA-PKcs in regulating autoimmune responses and maintaining AIRE-dependent tolerance in human. Disclosure of interest None declared.
Highlights
PRKDC encodes for DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a kinase that forms part of a complex (DNA-PK) crucial for DNA double-strand break (DSB) repair and V(D)J recombination
PRKDC mutations associated with immunodeficiency, granuloma and aire-dependent autoimmunity
We sought to understand the causes of an inflammatory disease with granuloma and autoimmunity, associated to decreasing T and B cell counts over time diagnosed in two unrelated patients
Summary
PRKDC encodes for DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a kinase that forms part of a complex (DNA-PK) crucial for DNA double-strand break (DSB) repair and V(D)J recombination. PRKDC mutations associated with immunodeficiency, granuloma and aire-dependent autoimmunity From 21st European Pediatric Rheumatology (PReS) Congress Belgrade, Serbia.
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