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Protective Effect Against Cancer of Antibodies to the Large Subunits of Both RNA Polymerases I and III in Scleroderma
Author(s) -
Shah Ami A.,
Laiho Marikki,
Rosen Antony,
CasciolaRosen Livia
Publication year - 2019
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40893
Subject(s) - cancer , medicine , autoantibody , antibody , scleroderma (fungus) , ovarian cancer , autoimmunity , immunology , cancer research , inoculation
Objective While compelling data suggest a cancer‐induced autoimmunity model in scleroderma patients with anti– RNA polymerase III large subunit (anti‐ RPC 155) antibodies, ~85% of these patients do not manifest cancer. This study was undertaken to determine whether additional autoantigens are targeted in anti‐ RPC 155–positive scleroderma patients without detectable cancer. Methods The study included 168 scleroderma patients with anti‐ RPC 155 antibodies (80 with a history of cancer and 88 with no cancer diagnosis after >5 years of follow‐up). Thirty‐five sera (17 from patients with cancer and 18 from patients without cancer) were randomly selected for autoantibody discovery using immunoprecipitation ( IP ). An ~194‐kd band was enriched in the subgroup without cancer; this was identified as RNA polymerase I large subunit ( RPA 194). Results RPA 194 generated by in vitro transcription/translation was used for IPs performed on the entire cohort to test whether anti‐ RPA 194 was enriched among anti‐ RPC 155–positive patients without cancer. Anti‐ RPA 194 antibodies were significantly more common in the group without cancer (16 [18.2%] of 88) than in the group with cancer (3 [3.8%] of 80) ( P = 0.003). Patients with both anti‐ RPA 194 and anti‐ RPC 155 were significantly less likely to have severe gastrointestinal disease than patients with anti‐ RPC 155 only (26.3% versus 51.0%; P = 0.043). Conclusion Anti‐ RPA 194 antibodies are enriched in anti‐ RPC 155–positive scleroderma patients without cancer. Since somatic mutations in the gene encoding RPC155 in cancer in scleroderma patients appears to play a role in immune response initiation against RPC 155 in those patients, these data raise the possibility that the development of immune responses to both RPC 155 and RPA 194 may influence clinical cancer emergence. Further study is required to define whether different autoantibody combinations have utility as tools for cancer risk stratification in scleroderma.