Diagnosis and risk stratification in patients with anti-RNP autoimmunity

INTRODUCTION: Anti-RNP autoantibodies occur either in Mixed Connective Tissue Disease (MCTD) (with a frequently favorable prognosis), or in systemic lupus (SLE) cases with aggressive major organ disease. It is uncertain how to assess for the risk of severe disease in anti-RNP+ patients. METHODS: Following IRB-approved protocols, clinical data and blood was collected from patients with known or suspected anti-RNP autoimmunity and normal controls in a cohort study. Samples were screened for parameters of immune activation. Groups were compared based on clinical diagnoses, disease classification criteria, disease activity, and specific end-organ clinical manifestations. RESULTS: 97% of patients satisfying Alarcon-Segovia MCTD criteria also met SLICC SLE criteria, while 47% of the anti-RNP+ SLE patients also met MCTD criteria. Among SLICC SLE patients, MCTD criteria were associated with reduced rates of renal disease (Odds Ratio 4.3, 95% confidence interval 1.3–14.0), increased rates of Raynaud’s Phenomenon (OR 3.5, 95% c.i. 1.3–9.5), and increased serum BCMA, TACI, and TNFa levels. Circulating immune markers and markers of Type I Interferon activation were not effective at distinguishing clinical subgroups. CONCLUSIONS: Among anti-RNP patients, the question of MCTD versus SLE is not either/or: most MCTD patients also have lupus. MCTD classification criteria (but not a broad set of immune markers) distinguish a subset of SLE patients at reduced risk for renal disease