A Report of 2 Cases of Kidney Involvement in ADA2 Deficiency: Different Disease Phenotypes and the Tissue Response to Type I Interferon

Adenosine deaminase 2 (ADA2) deficiency is a rare autosomal recessive disease, caused by loss-of-function mutations in the ADA2 gene, and is considered a monogenic form of polyarteritis nodosa (PAN) with frequently positive type I interferon (IFN-I) signature. Renal manifestations in ADA2 deficiency are poorly characterised. We herein report two cases of ADA2 deficiency with different kidney patterns due respectively to a predominantly macroscopic and microscopic vasculopathy, and review the literature on kidney disease in ADA2 deficiency. Patient 1 presented with a spontaneous peri-renal haematoma; angiography demonstrated multiple micro-aneurysms but no further defects of the renal parenchyma; his kidney function remained normal. Patient 2 experienced slowly deteriorating kidney function and proteinuria. No major angiographic abnormalities were detected, while kidney biopsy revealed massive vasculopathy resembling chronic thrombotic microangiopathy (TMA) of the small and medium-sized vessels. Both patients had a positive peripheral IFN-I signature. We stained Patient 2's kidney biopsy for the IFN I-induced protein MXA: this was markedly expressed within endothelial cells, especially in vessels with TMA, and in infiltrating T-cells. Our findings confirm that the kidney phenotype of ADA2 deficiency results from small and medium-sized vessel vasculopathy and suggest that IFN-I may be involved in the pathogenesis of kidney lesions.