Partial RAG deficiency in a patient with varicella infection, autoimmune cytopenia, and anticytokine antibodies

RAG1/2 deficiency has a broad phenotypic spectrum including combined immunodeficiency with granulomatous disease and/or autoimmunity (CID-G/AI) where milder impairment of RAG1/2 recombinase activity results in relatively preserved T- and B-lymphocyte counts and immunoglobulin levels; however, naive T-cell counts progressively decrease.5 Therefore, measurement of T-cell receptor excision circles (TRECs), reflecting naive T-cell count, may identify these patients at birth in asymptomatic stage (via newborn screening) or later in life in the midst of infectious or autoimmune complications. [...]in countries where newborn screening for SCID is not available, serological testing with a panel of anticytokine autoantibodies targeting IFN-α, IFN-ω, and IL-12 may serve as a complementary tool to raise suspicion for an underlying RAG deficiency with CID-G/AI phenotype in a child with a history of refractory AIC with severe viral infections.3 Hereby we report a 26-month-old female with partial RAG deficiency, nonvaccine strain varicella infection, and severe refractory AIC and discuss our diagnostic approach in Hungary where newborn screening for SCID is not available. [...]in countries where TREC screening is not available, such as Hungary, using autoantibody profiling with anticytokine antibody testing may help to identify those with an underlying combined immunodeficiency, such as partial RAG deficiency, and expedite early recognition and confirmation by genetic testing, which is essential for timely preparation for stem cell transplantation and favorable outcomes.Appendix Results Normal value CD3 152/μL 900-4,500/μL CD4+ 92.8/μL 500-2,400/μL CD8+ 32.5/μL 300-1,600/μL CD4+CD45RA+ 19% >60% CD19+ 213.8/μL 200-2,100/μL CD16+ CD 56+ 444.7/μL 100-1,000/μL IgG 1,997 mg/dL 453-916 mg/dL IgA 0.01 mg/dL 20-100 mg/dL IgM 128 mg/dL 19-146 mg/dL Table I Lymphocyte subsets and immunoglobulin levels at first assessment of the child Pt Phenotype Mutation Live vaccination Onset of VZV or CMV infection Onset of autoimmune cytopenia Time diffence between infection and AIC Age of diagnosis of RAG deficiency Time difference between AIC and diagnosis of RAG deficiency Immune modulation HCT Age at testing for autoantibodies Anticytokine antibodies Reference 1 Leaky SCID RAG 1 a. R474C b. K983NfsX9 None VZV—20 mo Coombs+ AIHA— 21 mo 1 mo 24 mo 3 mo Nonresponsive to GCSF.