Background/Purpose:

Anti-Th/To antibodies (anti-Th) are one of the specificities that show nucleolar staining in indirect immunofluorescence antinuclear antibody test. Anti-Th is associated with systemic sclerosis (SSc), mainly the limited cutaneous variant.  However, cases of anti-Th also have been reported in other diseases. Although known for over 20 years, anti-Th is rarely used in routine testing algorithms because immunoprecipitation (IP) is not widely available. One of the components of the Th-complex, namely Rpp25, has been reported as a major autoantigen, recognized by ~80% of anti-Th positive sera in ELISA.  The goal of the study was to better characterize the clinical features associated with anti-Th in various autoimmune disease cohorts as identified by anti-Rpp25 ELISA followed by confirmation IP.

Methods:

Patients enrolled were seen at Autoimmune Disease Center from 2000 to 2012.  All SSc patients’ sera had previously undergone RNA-IP. Patients with other rheumatic diseases including 462 systemic lupus erythematosus (SLE), 131 autoimmune inflammatory myopathy (AIM), 63 primary Sjogren’s syndrome (SS) and 138 Rheumatoid Arthritis (RA) were screened by anti-Rpp25 ELISA. Borderline and positive cases underwent confirmatory IP. Additionally, anti-nucleolar staining ANA positives were tested by RNA-IP. The clinical characteristics of the anti-Th (+) patients were then more closely evaluated by reviewing database and chart records.

Results:

Overall, anti-Th was confirmed in 17 cases (7 SSc and 10 non-SSc) via Rpp25 ELISA and IP.  Prevalence of anti-Th was 6% (7/125) in SSc, 0.6% (3/462) in SLE, 0.7% (1/131) in AIM, 0% (0/138) in RA, 3% (2/63) in SS and 4 others without a rheumatologic diagnosis. Of the 17 anti-Th patients, 15 were Caucasian and 2 were African American and had SLE.  The anti-Th SSc patients were mainly the limited cutaneous variant (4/7) and none of them had interstitial lung disease (ILD) or pulmonary arterial hypertension (PAH).  Of the non-SSc patients with other rheumatologic diagnoses 3 had SLE, 2 had SS and 1 had AIM but some also had features associated with SSc: 2/6 ILD, 3/6 Raynaud’s (RP), 1/6 telangiectasia (TG), 1/6 pitting scars (PS).  Four other non-SSc patients without a rheumatologic diagnosis had features typical of SSc: 3/4 RP, 1/4 PS, 3/4 TG, 1/4 ILD, 1/4 PAH which may represent sine-SSc variant. 

Conclusion:

Based on anti-Rpp25 ELISA and IP screening, anti-Th is fairly specific for SSc. However, anti-Th was also found in other connective tissue diseases with features associated with SSc and some cases had feature of SSc without sclerodermatous skin changes, thus may be classified sine-SSc.