Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Non-Jo-1 Anti-Synthetase Autoantibodies Are Not Specific for Myositis and Are Associated with Poor Survival.
Cassidy1, Elaine A., Aggarwal3, Rohit, Fertig3, Noreen, Lucas3, Mary, Ascherman3, Dana P., Oddis2, Chester V.
Children's Hospital of Pittsburgh Division of Rheumatology, Pittsburgh, PA
University of Pittsburgh, Pittsburgh, PA
University of Pittsburgh School of Medicine Division of Rheumatology and Clinical Immunology, Pittsburgh, PA
Purpose:
To compare clinical features and outcome in patients (pts) with Jo-1 vs. non-Jo-1 anti-tRNA synthetase autoantibodies (anti-synAb).
Methods:
All anti-synAb positive pts in a Connective Tissue Disease (CTD) Registry were included regardless of initial or subsequent CTD diagnosis. Demographic and clinical data were collected from the medical record and registry. Current status and cause of death was determined by query of the National Death Index or Social Security Death Index, and medical record. For lung survival an endpoint of lung transplant or death was used. Survival was compared by Kaplan-Meier and log rank test. Cox proportional hazards ratios were calculated to compare survival after controlling for co-variates.
Results:
202 of 3880 (5.2%) CTD pts were anti-synAb positive [122 Jo-1; 80 non-Jo-1 (35 PL-12; 25 PL-7; 9 EJ; 6 KS; 5 OJ]. Both groups had similar demographic features (Table 1), but non-Jo-1 pts had a greater delay in diagnosis, and a diagnosis at 1st visit in 60% that did not include PM or DM.
Table 1. Demographic and Clinical Features of Synthetase Cohort
| Diagnoses at First Visit | Median Delay in Dx from 1st | |||||||
|---|---|---|---|---|---|---|---|---|
| Mean Age at Symptom Onset (yrs) | % Female | % Caucasian | Myositis (%) | Overlap or UCTD | (%) | SSc (%) | CTD Symptom (mths; IQR) | |
| Jo-1 (n = 122) | 45 | 67 | 82 | 83 | PM 58 DM 25 | 17 | 0 | 6 (2–13) |
| non-Jo-1 (n = 80) | 46 | 70 | 75 | 40 | PM 23 DM 17 | 49 | 11 | 9 (3–24) |
| p value | NS | NS | NS | p < 0.0002 | p = 0.03 | |||
| NS = not significant; IQR-interquartile ratio; UCTD = undifferentiated connective tissue disease | ||||||||
Sixty-six pts are deceased with pulmonary fibrosis and pulmonary hypertension the most common causes. Twelve pts (7 Jo-1; 5 non-Jo-1) underwent lung transplantation. Although a pulmonary cause of death was similar between Jo-1 and non-Jo-1 cohorts, the 5 and 10 yr unadjusted cumulative and median survival was significantly different.
Table 2. Outcome and Survival of Synthetase Cohort
| Pulmonary Cause of Death | Cumulative Survival | |||||
|---|---|---|---|---|---|---|
| Deceased (%) | Mean Age at Death (yrs) | Fibrosis PHT | 5 year (%) | 10 year (%) | Median Survival (yrs; IQR) | |
| Jo-1 (n = 122) | 36 (30%) | 58 +/-14 | 19/36 | 90 | 74 | 15 (7.9–21.3) |
| 16/36 3/36 | ||||||
| non-Jo-1 (n = 80) | 30 (38%) | 62 +/-14 | 20/30 | 70 | 48 | 9 (4.3–18) |
| 16/30 4/30 | ||||||
| p value | NS | NS | P <0.01 | P <0.01 | ||
| PHT = pulmonary hypertension | ||||||
After adjusting for gender, ethnicity and age at diagnosis, non-Jo-1 pts had decreased survival (HR 1.86; p=0.02; 95% CI 1.10–3.14) and lung survival (HR 1.96; p= 0.008; 95% CI 1.19–3.23) compared to Jo-1 pts. After adjusting for diagnosis delay, non-Jo-1 pts had decreased lung survival (HR 1.77; p= 0.03; 95% CI 1.06–2.97), and a trend toward decreased cumulative survival (HR 1.71; p =0.051; 95% CI 1.00– 2.96). Non-Jo-1 PM pts had the worst cumulative survival (HR 3.75; p=0.02; 95% CI 1.21– 11.68) and lung survival (HR 2.84; p=0.01; 95% CI 1.23–6.52).
Conclusions:
In the largest reported anti-synAb+ cohort to date, the previously described myositis specificity of non-Jo-1 anti-synAb was not supported. Non-Jo-1 pts have decreased cumulative survival and lung survival compared to Jo-1 pts, with non-Jo-1 pts with PM having the worst cumulative and lung survival. The difference in survival may be attributable to a delay in diagnosis in the non-Jo-1 group due to nonspecific symptoms at presentation and negative commercial antibody testing. Increased awareness of this CTD subset among rheumatologists and pulmonologists is emphasized.
To cite this abstract, please use the following information:
Cassidy, Elaine A., Aggarwal, Rohit, Fertig, Noreen, Lucas, Mary, Ascherman, Dana P., Oddis, Chester V.; Non-Jo-1 Anti-Synthetase Autoantibodies Are Not Specific for Myositis and Are Associated with Poor Survival. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :929
DOI: 10.1002/art.28697
