Background/Purpose: Although some studies suggest a possible association between clinical characteristics and isotypes of anticentromere antibodies (ACA) in patients with systemic sclerosis (SSc), characteristics of ACA response have not been described thoroughly. Therefore, we evaluated whether ACA isotype expression and levels: 1. associate with disease severity, 2. differ between patients with very early SSc and SSc, and 3. can identify very early SSc patients that will progress to SSc.

Methods: All ACA IgG+ patients fulfilling the American College of Rheumatology (ACR) 2013 criteria for SSc and ACA+ IgG patients with very early SSc (based on ACA, Raynaud and puffy fingers or abnormal nailfold capillaroscopy but not fulfilling ACR 2013 criteria), from the prospective SSc cohorts from the Leiden University Medical Centre (LUMC), the University Hospital Zurich, and the Oslo University Hospital were included. Presence and levels of ACA IgM and IgA were determined by J.B. at the LUMC. Patients were categorized in three groups according to disease severity: very early SSc, SSc without organ involvement, and SSc with organ involvement. Organ involvement was defined as any of: digital ulcers, interstitial lung disease, pulmonary arterial hypertension, renal crisis and myocardial involvement. Associations between isotype presence and levels and disease severity were evaluated with logistic regression, with adjustment for age and disease duration. ACA response characteristics were compared between very early SSc patients that progressed to ACR 2013 criteria and those who did not.

Results: ACA characteristics were measured in 445 ACA IgG + patients. Ninety patients (20%) had very early SSc and 355 (80%) fulfilled the ACR criteria, in which 41% (n=144) were classified as SSc with organ involvement (Table 1). At baseline, 86% of patients were ACA IgM+, and 75% were ACA IgA+. Very early SSc patients show lowest titers of IgM and IgG. In contrast, SSc patients with organ involvement most often express ACA IgM and show highest titers of all isotypes, indicating a more active, specific B cell responses (Table 1). With adjustment for disease duration and age, ACA IgG levels were significantly higher in SSc patients vs. very early SSc, and in SSc patients with organ involvement vs. SSc without organ involvement (Table 2). Of all very early SSc patients with follow-up (n=70; median FU 2.1 year) 30% progressed to SSc, mostly due to skin progression (88%), and 23% developed lung involvement, after a median period of 4.3 year. As age and follow-up duration were significantly higher in the progressors we were underpowered to analyse isotype characteristics by means of regression. However, again, we observed a trend for higher ACA IgG levels in the very early SSc patients progressing to SSc fulfilling ACR 2013 criteria.

Conclusion: Here we show in a large multicentre SSc cohort that ACA IgG levels increase with increasing disease severity, from very early SSc, to SSc without organ involvement and SSc with organ involvement. Our data indicate that ACA+ SSc specific B cell responses are potentially involved in disease-relevant pathogenic processes. In addition, ACA response characteristics might also be useful for risk stratification in clinical practice.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anticentromere-antibody-levels-and-isotypes-associate-with-disease-severity-in-systemic-sclerosis/