Cancer in Systemic Sclerosis: Analysis of Antibodies Against Components of the Th/To Complex

Abstract

Objective The aim of this study is to describe 4 of the most common autoantibodies against components of the Th/To complex: human POP1 (hPOP1), RPP25, RPP30, and RPP40. We report their prevalence and clinical characteristics in a systemic sclerosis (SSc) population, and determine whether these specificities are associated with cancer. Methods A case–control study was performed using data from the Johns Hopkins Scleroderma Center Cohort. A total of 804 adult patients with SSc were included; 401 SSc patients with no history of cancer after at least 5 years of disease were compared to 403 SSc patients who ever had a history of cancer. Antibodies against hPOP1, RPP25, RPP30, and RPP40 were assayed by immunoprecipitation of 35S‐methionine–labeled proteins generated by in vitro transcription/translation. Demographic and clinical characteristics were compared between groups. Results Of 804 patients, 67 (8.3%) had antibodies against any component of the Th/To complex. Patients with antibodies to any component were significantly more likely to have limited cutaneous disease, less likely to have tendon friction rubs, and more likely to have findings consistent with interstitial lung disease or pulmonary hypertension. Patients with antibodies against hPOP1, RPP25, RPP30, and/or RPP40 were significantly less likely to develop cancer within 2 years of SSc onset (0% versus 11% of antibody‐negative patients; P = 0.009). Conclusion SSc patients who produce autoantibodies to components of the Th/To complex have a clinical phenotype characterized by limited cutaneous disease and pulmonary involvement. Our findings show that the presence of any Th/To autoantibody may have a protective effect against contemporaneous cancer.

Development of Pulmonary Hypertension in Over One‐Third of Patients With Th/To Antibody–Positive Scleroderma in Long‐Term Follow‐Up

“…Recently, several SSc studies have described anti‐Th/To antibody frequency in various populations. The incidence of anti‐Th/To antibody positivity ranged from 2% to 8% in studies in SSc patients who were American, Algerian, or Han Chinese (29–31). A study comparing a total of 260 SSc patients who were African Brazilian or White Brazilian showed a higher proportion of anti‐Th/To positivity among White Brazilian patients (5% compared to 2% of African Brazilian patients) that was not statistically significant (32).…”

Anti‐Th/To Antibodies: Association With Lung Disease and Potential Protection From Systemic Sclerosis–Related Cancer? Comment on the Article by Mecoli et al

“…Autoantibodies in systemic sclerosis (SSc) can help stratify patients into more clinically relevant subsets (1). We read with interest the article by Mecoli et al on their study of 804 adult SSc patients (2), which represents one of the largest studies of anti‐Th/To antibodies. The prevalence of autoantibodies to 4 in vitro transcribed and translated Th/To components (hPOP1, RPP25, RPP30, and RPP40) as assessed by immunoprecipitation (IP) is consistent with results from previous studies (3) (Figure 1).…”

“…Given the importance of the study findings, additional data extraction and further studies could benefit the scientific field. Since the IP technique used (2) is not widely available, interassay comparisons would be informative with regard to the consistency of the results with those obtained using commercially available IP (in vitro diagnostic/research use only) and other Th/To immunoassays (e.g., the line immunoassay used for selected analyses in this study a chemiluminescence immunoassay [3], and/or novel particle‐based multianalyte technology assays [1]). Furthermore, the study established the specificity of IP based on only 34 healthy controls, although previous studies demonstrated that some Th/To complex subunits are targeted by antibodies in patients with other autoimmune conditions (3).…”

Long‐term risk of cancer development among anti‐Th/To antibody–positive systemic sclerosis patients: comment on the article by Mecoli et al

“…We read with great interest the article by Dr. Mecoli and colleagues on the relationship between cancer and anti-Th/To antibodies in patients with systemic sclerosis (SSc) (1). Interestingly, the presence of anti-Th/To antibodies was reported to confer a protective effect against the development of cancer in patients with SSc.…”

“…One of our major concerns regarding the study by Mecoli et al (1) is that it lacks a description of the causes of death in the anti-Th/To antibody-positive SSc patients. Although none of the anti-Th/To antibody-positive SSc patients from our study have died to date, 8 (27.6%) of 29 deaths in our SSc cohort were cancer-related.…”