Autoantibodies to Rpp25 (Th/To) are specific markers for systemic sclerosis and are associated with limited cutaneous disease and young age at disease onset[MM1] 

Boyang Zheng⁴, Martial Koenig⁴, Michael Mahler¹,

¹ Inova Diagnostics, INC.  San Diego, CA, USA;

² Department of Medicine, McGill University, Montreal, Quebec, Canada

Background/Purpose:

Antinuclear antibodies (ANA), present in 80-90% of systemic sclerosis (SSc) patients, are important for disease diagnosis. Of particular utility are those with SSc-specific and SSc-associated antibodies, including anti Th/To amongst others (i.e. antibodies to centromere, Scl-70, RNA Pol-III, PM/Scl, Ro52/TRIM21 and U1RNP). However, in a significant minority of ANA positive SSc patients, no fine specificities are detected using conventional diagnostic protocols. Recently, it was found that anti-Rpp25 antibodies are an important autoantigenic component of the Th/To complex. However, no FDA cleared assay is available for the detection of anti-Th/To antibodies. Consequently, the present study aimed to analyze a large well characterized Canadian SSc patient cohort in comparison to other disease control groups for antibodies to Rpp25 in a standardized assay.

Methods:

Sera from 320 Canadian SSc patients [48 diffuse cutaneous (dc) SSc, 223 limited cutaneous (lc) SSc and 49 sine SSc] and various disease controls (n=889) were tested for anti-Rpp25 antibodies by a bead based immunoassay (research use only, Inova Diagnostics, US).

Results:

Anti-Th/To antibodies were significantly more common and present in higher titers in SSc patients compared to all controls (p<0.05). The prevalence in SSc and in the different control groups is summarized in the figure below.

Receiver operating characteristic (ROC) analysis showed an area under the curve of 0.70 (95% Confidence interval 0.67-0.73). The sensitivity and specificity for SSc was 9.7% (95% CI 6.9-13.4%) and 99.0% (95% CI 98.1-99.5%), respectively. The odds ratio for SSc was 10.6 (95% CI 5.1-22.3). Anti-Rpp25 antibodies were present in 0/48 dcSSc (0.0%), in 27/223 lcSSc (12.1%) and in 4/49 (8.2%) sine SSc patients. The difference between lcSSc and dcSSc was significant (p=0.01). In addition, anti-Rpp25 antibodies were associated with a younger age at SSc disease onset (34.3 vs. 39.8 years; p=0.048).

Conclusion:

Autoantibodies to Rpp25 as part of the Th/To autoantigen show high specificity for SSc and define a subset of SSc with lcSSc and younger age of disease onset.