Vasculitis as a Major Morbidity Factor in Patients With Partial RAG Deficiency

Area of Science:

• Immunology
• Genetics
• Pediatrics

Background:

• Vasculitis is a severe complication in primary immunodeficiencies (PIDs), particularly severe and combined immunodeficiencies (SCIDs).
• Understanding of vasculitis in partial Recombination Activating Gene (RAG) deficiency, a SCID variant, is limited.
• Systematic evaluation of diagnostic and therapeutic approaches for vasculitis in partial RAG deficiency is lacking.

Purpose of the Study:

• To define clinical and laboratory features of vasculitis in partial RAG deficiency.
• To evaluate treatment outcomes for vasculitis in this patient group.
• To improve diagnostic and therapeutic strategies for vasculitis in partial RAG deficiency.

Main Methods:

• Retrospective analysis of 62 patients with partial RAG deficiency.
• Clinical data collection on vasculitis onset, manifestations, and complications.
• Laboratory testing for autoantibodies (cytokine, ANCA) and genetic diagnosis of RAG deficiency.

Main Results:

• Vasculitis occurred in 13% of patients, often as the initial sign, leading to significant end-organ damage.
• Viral infections frequently preceded vasculitis, which was typically small-vessel and non-granulomatous.
• High prevalence of autoantibodies against cytokines (80%) and low ANCA positivity (>80%) were observed; diagnosis was delayed up to 2 years.

Conclusions:

• Vasculitis is a prevalent and high-morbidity complication in partial RAG deficiency.
• Partial RAG deficiency should be considered in early-onset systemic vasculitis differential diagnoses.
• Diagnostic serology can be misleading; testing for cytokine autoantibodies is recommended alongside conventional autoantibody screening.