Diagnosis and risk stratification in patients with anti-RNP autoimmunity

Lupus. 2015 Sep;24(10):1057-66. doi: 10.1177/0961203315575586. Epub 2015 Mar 2.


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.

Keywords: Systemic lupus erythematosus; classification criteria; inflammation; mixed connective tissue disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Antibodies, Antinuclear / immunology
  • Autoantibodies / blood*
  • Autoantibodies / metabolism
  • Biomarkers / blood
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Gene Expression
  • Humans
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Middle Aged
  • Mixed Connective Tissue Disease / blood
  • Mixed Connective Tissue Disease / diagnosis*
  • Mixed Connective Tissue Disease / immunology
  • RNA / blood
  • RNA / genetics
  • Raynaud Disease / immunology
  • Ribonucleoproteins / antagonists & inhibitors*
  • Ribonucleoproteins / immunology
  • Risk Assessment / methods


  • Antibodies, Antinuclear
  • Autoantibodies
  • Biomarkers
  • Ribonucleoproteins
  • RNA