Association Observed Between Centromere and Topoisomerase Antibody Expression and Microangiopathy in SSc

There is an association between specific anticentromere antibodies (ACA) and antitopoisomerase antibodies (ATA) responses and the degree of microangiopathy in systemic sclerosis (SSc), according to study results published in The Journal of Rheumatology. According to the researchers, this association indicated that dysregulated B-cell responses and microvascular damage interact with each other in SSc pathophysiology.

Previous studies have shown that increased severe microangiopathy has been associated with worse disease outcomes for patients with SSc. In this study, researchers evaluated whether ACA and ATA isotype expression was associated with degree of microangiopathy in SSc and determined the effect of activated immune responses for the prediction of organ involvement.

In this Dutch observational cohort study, a total of 231 patients with SSc (129 ACA+ and 102 ATA+) were included. The average age of patients was 55±14 years, a majority of whom were women (80.5%). Levels of ACA and ATA immunoglobulin (Ig) G, IgA and IgM were measured in serum samples of ACA IgG+ and ATA IgG+ patients with SSc. The degree of microangiopathy was determined based on nailfold videocapillaroscopy (NVC) images, with SSc “late” pattern reflecting more severe microangiopathy. Researchers assessed the association between ATA and ACA isotype expression and NVC patterns. Logistic regression analyses were performed, with autoantibodies, clinical characteristics, isotype expression and ACA resp. [sic] ATA IgG, IgM and IgA levels NVC patterns as independent and dependent variables, respectively; the variables were adjusted for age, sex, and disease duration.

Isotype levels and degree of microangiopathy were evaluated for 164 patients (ACA, n=100; ATA, n=64). Logistic regression confirmed the association between more severe microangiopathy and organ involvement, including interstitial lung disease (OR, 3.2; 1.1-9.7), pulmonary arterial hypertension (OR, 5.25; 1.69-16.36), and digital ulcers (OR, 3.1; 1.4-6.6). Patients who were ATA+ vs ACA- were observed to have more severe microangiopathy (OR, 2.09; 1.05-4.13). Furthermore, the results indicated a possible association between characteristics of specific antibody responses and degree of microangiopathy. Compared with patients who expressed ACA IgM and/or IgA, levels of ACA IgG and ATA IgM, those who exclusively expressed ACA IgG showed a trend towards less severe microangiopathy.

Study limitations included that treatment before inclusion in the trial was uncontrolled, previous immunosuppressive medications may be possible confounders, and only patients who showed ATA IgG or ACA IgG positivity at baseline were included, thus no conclusions could be drawn for the remaining antibody subgroups in SSc.

Researchers concluded, “Further research is needed to confirm these observations, and to identify the possible mechanism behind this association.”

Reference

Van Leeuwen NM, Wortel CM, Fehres CM, Bakker JA, Scherer HU, Toes REM, et al. Association between centromere and topoisomerase specific immune responses and the degree of microangiopathy in systemic sclerosis [published online June 1, 2020]. J Rheumatol. doi:10.3899/jrheum.191331