Background/Purpose: Detection of serum autoantibodies is useful in diagnosis, disease subgrouping, and prediction of subsequent organ involvement and prognosis in patients with systemic sclerosis (SSc). Currently, SSc-related autoantibodies consisted of at least 9 specificities, which are identified in ~80% of the entire SSc population, suggesting the possibility that other autoantibodies remain undiscovered. In this study, we have identified a novel SSc-related antibody against a complex consisting of RuvBL1 and RuvBL2 (RuvBL1/2) and evaluated its clinical correlations.

Methods: We first analyzed 316 consecutive patients with SSc, 290 disease controls including, patients with SLE, PM, DM, RA, interstitial lung disease alone, or autoimmune hepatitis, and 50 healthy subjects (Kanazawa cohort). Autoantibody specificities were analyzed using RNA and protein immunoprecipitation assays. Autoimmune targets were affinity-purified using patients’ sera and subjected to liquid chromatography-mass spectrometry. SSc patients in two additional cohorts (Keio and Pittsburgh) were also included in analysis for evaluating prevalence and clinical correlations.

Results: By protein immunoprecipitation assay, 6 SSc sera (1.9%) reacted with doublets with molecular weights around 50 kDa. This antibody specificity was not detected in any sera obtained from a total of 290 disease controls or 50 healthy controls. Liquid chromatography-mass spectrometory of the partially purified autoantigen and additional immunoblots-based analysis revealed that this antibody specificity recognized RuvBL1/2, which is involved in many important cellular processes, such as transcription and DNA repair. Anti-RuvBL1/2 antibody was also found in 4 (1.5%) of 272 consecutive SSc patients in the Keio cohort, and in 5 (1.1%) of 463 consecutive SSc patients in the Pittsburgh cohort. In all three cohorts, SSc in overlap was the predominant disease subset in patients with anti-RuvBL1/2 (P < 0.0001). Diffuse skin thickening was more common in patients with anti-RuvBL1/2 in general and in those with SSc in overlap, compared to those without (P < 0.04). In terms of organ involvement, skeletal muscle involvement was frequent in patients with anti-RuvBL1/2 than those without (P < 0.0003). When we examined potential differences in clinical correlations between anti-RuvBL1/2 and other SSc-related antibodies associated with inflammatory myopathy, such as anti-PM-Scl and anti-Ku, age at onset was older and the proportion of males was higher in patients with anti-RuvBL1/2 than in those without (P = 0.0001 and 0.002, respectively). In patients with anti-RuvBL1/2, diffuse skin thickening was more prevalent (P = 0.004), the maximum mRSS in patients with diffuse cutaneous involvement was greater (P = 0.001), and dermatomyositis rashes were less common (P= 0.01), compared to patients with anti-PM-Scl or anti-Ku. 

Conclusion: We have identified a novel SSc-related antibody reactive with a RuvBL1/2 complex, which is associated with a unique combination of clinical features, including myositis overlap and diffuse cutaneous involvement.

---

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantibodies-to-ruvbl1-and-ruvbl2-a-novel-systemic-sclerosis-related-antibody-associated-with-diffuse-cutaneous-and-skeletal-muscle-involvement/