Dataset Information

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 ³⁵ S-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.

SUBMITTER: Mecoli CA

PROVIDER: S-EPMC7884482 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe incidence and mortality of lung cancer are the highest among all cancers. Patients with systemic sclerosis show a four-fold greater risk of lung cancer than the general population. However, the underlying mechanism remains poorly understood.MethodsThe expression profiles of 355 peripheral blood samples were integratedly analyzed, including 70 cases of lung cancer, 61 cases of systemic sclerosis, and 224 healthy controls. After data normalization and cleaning, differentially expressed genes (DEGs) between disease and control were obtained and deeply analyzed by bioinformatics methods. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed online by DAVID and KOBAS. The protein-protein interaction (PPI) networks were constructed from the STRING database.ResultsFrom a total of 14,191 human genes, 299 and 1644 genes were identified as DEGs in systemic sclerosis and lung cancer, respectively. Among them, 64 DEGs were overlapping, including 36 co-upregulated, 10 co-downregulated, and 18 counter-regulated DEGs. Functional and enrichment analysis showed that the two diseases had common changes in immune-related genes. The expression of innate immune response and response to virus-related genes increased significantly, while the expression of negative regulation of cell cycle-related genes decreased notably. In contrast, the expression of mitophagy regulation, chromatin binding and fatty acid metabolism-related genes showed distinct trends.ConclusionsStable differences and similarities between systemic sclerosis and lung cancer were revealed. In peripheral blood, enhanced innate immunity and weakened negative regulation of cell cycle may be the common mechanisms of the two diseases, which may be associated with the high risk of lung cancer in systemic sclerosis patients. On the other hand, the counter-regulated DEGs can be used as novelbiomarkers of pulmonary diseases. In addition, fat metabolism-related DEGs were consideredto be associated with clinical blood lipid data.