Diagnosis and risk stratification in patients with anti-RNP autoimmunity.
BACKGROUND
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.
Division of Rheumatology, University of Miami Miller School of Medicine, Miami, USA.
M F
MF
Carpintero
Miami VA Medical Center, Miami, USA.
L
L
Martinez
Division of Rheumatology, University of Miami Miller School of Medicine, Miami, USA.
I
I
Fernandez
Division of Rheumatology, University of Miami Miller School of Medicine, Miami, USA.
A C Garza
AC
Romero
Division of Rheumatology, University of Miami Miller School of Medicine, Miami, USA.
C
C
Mejia
Division of Rheumatology, University of Miami Miller School of Medicine, Miami, USA.
Y J
YJ
Zang
Eli Lilly and Company, Indianapolis, USA.
R W
RW
Hoffman
Division of Rheumatology, University of Miami Miller School of Medicine, Miami, USA Miami VA Medical Center, Miami, USA egreidinger@med.miami.edu.
E L
EL
Greidinger
D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D012313:RNA / Q000097:blood / Q000235:genetics; D011928:Raynaud Disease / Q000276:immunology; D012261:Ribonucleoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D018570:Risk Assessment / Q000379:methods
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D015415:Biomarkers; D012261:Ribonucleoproteins; D012313:RNA
Systemic lupus erythematosus; classification criteria; inflammation; mixed connective tissue disease