Diagnosis and risk stratification in patients with anti-RNP autoimmunity

• Published in: Lupus 2015-09, Vol.24 (10), p.1057-1066
• Main Authors: Carpintero, M F, Martinez, L, Fernandez, I, Romero, A C Garza, Mejia, C, Zang, Y J, Hoffman, R W, Greidinger, E L
• Format: Article
• Language: English
• Subjects: Adult; Antibodies; Antibodies, Antinuclear - immunology; Antigens; Autoantibodies - blood; Autoantibodies - metabolism; Biomarkers - blood; Case-Control Studies; Cohort Studies; Connective tissue diseases; Female; Gene Expression; Humans; Interferon; Kidney diseases; Lung diseases; Lupus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - diagnosis; Lupus Erythematosus, Systemic - immunology; Male; Medical laboratories; Middle Aged; Mixed Connective Tissue Disease - blood; Mixed Connective Tissue Disease - diagnosis; Mixed Connective Tissue Disease - immunology; Pulmonary hypertension; Raynaud disease; Raynaud Disease - immunology; Review boards; Rheumatology; Ribonucleoproteins - antagonists & inhibitors; Ribonucleoproteins - immunology; Risk Assessment - methods; RNA - blood; RNA - genetics
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/0961203315575586

Introduction Anti-RNP autoantibodies occur either in mixed connective tissue disease (MCTD) (with a frequently favorable prognosis), or in systemic lupus erythematosus (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 institutional review board-approved protocols, clinical data and blood were 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 Ninety-seven per cent of patients satisfying Alarcon-Segovia MCTD criteria also met Systemic Lupus International Collaborating Clinic (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 (OR) 4.3, 95% confidence interval (CI) 1.3–14.0), increased rates of Raynaud's phenomenon (OR 3.5, 95% CI 1.3–9.5) and increased serum B-cell maturation antigen, transmembrane activator and CAML interactor and TNFα 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.