{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:28:54Z","timestamp":1793320134556,"version":"4.5.0"},"reference-count":45,"publisher":"The Journal of Rheumatology","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) strongly associated with anti-RNA polymerase III antibody (ARA) autoantibodies. We investigated genetic susceptibility and altered protein expression in renal biopsy specimens in ARA-positive patients with SRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>ARA-positive patients (n = 99) with at least 5 years\u2019 follow-up (49% with a history of SRC) were selected from a well characterized SSc cohort (n = 2254). Cases were genotyped using the Illumina Human Omni-express chip. Based on initial regression analysis, 9 single-nucleotide polymorphisms (SNP) were chosen for validation in a separate cohort of 256 ARA-positive patients (40 with SRC). Immunostaining of tissue sections from SRC or control kidney was used to quantify expression of candidate proteins based upon genetic analysis of the discovery cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Analysis of 641,489 SNP suggested association of POU2F1 (rs2093658;\n                      <jats:italic>P<\/jats:italic>\n                      = 1.98 \u00d7 10\n                      <jats:sup>\u22125<\/jats:sup>\n                      ), CTNND2 (rs1859082;\n                      <jats:italic>P<\/jats:italic>\n                      = 5.58 \u00d7 10\n                      <jats:sup>\u22125<\/jats:sup>\n                      ), HECW2 (rs16849716;\n                      <jats:italic>P<\/jats:italic>\n                      = 1.2 \u00d7 10\n                      <jats:sup>\u22124<\/jats:sup>\n                      ), and GPATCH2L (rs935332;\n                      <jats:italic>P<\/jats:italic>\n                      = 4.92 \u00d7 10\n                      <jats:sup>\u22125<\/jats:sup>\n                      ) with SRC. Further, the validation cohort showed an association between rs935332 within the\n                      <jats:italic>GPATCH2L<\/jats:italic>\n                      region, with SRC (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.025). Immunostaining of renal biopsy sections showed increased tubular expression of GPATCH2L (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.026) and glomerular expression of CTNND2 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.026) in SRC samples (n = 8) compared with normal human kidney controls (n = 8), despite absence of any genetic replication for the associated SNP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Increased expression of 2 candidate proteins, GPATCH2L and CTNND2, in SRC compared with control kidney suggests a potential role in pathogenesis of SRC. For GPATCH2L, this may reflect genetic susceptibility in ARA-positive patients with SSc based upon 2 independent cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3899\/jrheum.190945","type":"journal-article","created":{"date-parts":[[2020,3,15]],"date-time":"2020-03-15T12:25:18Z","timestamp":1584275118000},"page":"1668-1677","source":"Crossref","is-referenced-by-count":26,"title":["Analysis of Anti-RNA Polymerase III Antibody-positive Systemic Sclerosis and Altered GPATCH2L and CTNND2 Expression in Scleroderma Renal Crisis"],"prefix":"10.3899","volume":"47","author":[{"given":"Edward P.","family":"Stern","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra G.","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Chinque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Acquaah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9533-7081","authenticated-orcid":false,"given":"David","family":"Gonz\u00e1lez-Serna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markella","family":"Ponticos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Voon H.","family":"Ong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korsa","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana I.","family":"Nihtyanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Harber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aine","family":"Burns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen D.","family":"Mayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shervin","family":"Assassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3975-8938","authenticated-orcid":false,"given":"Christopher P.","family":"Denton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2262","published-online":{"date-parts":[[2020,3,15]]},"reference":[{"key":"2022062017050995000_47.11.1668.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30933-9"},{"key":"2022062017050995000_47.11.1668.2","first-page":"8","article-title":"Relationship between cutaneous and pulmonary involvement in systemic sclerosis","volume":"24","author":"Morelli","year":"1997","journal-title":"J Rheumatol"},{"key":"2022062017050995000_47.11.1668.3","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.062901"},{"key":"2022062017050995000_47.11.1668.4","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcm052"},{"key":"2022062017050995000_47.11.1668.5","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.091048"},{"key":"2022062017050995000_47.11.1668.6","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/art.40809","article-title":"Generation of a core set of items to develop classification criteria for scleroderma renal crisis using consensus methodology","volume":"71","author":"Butler","year":"2019","journal-title":"Arthritis Rheum"},{"key":"2022062017050995000_47.11.1668.7","first-page":"106","article-title":"UK Scleroderma Study Group (UKSSG) guidelines on the diagnosis and management of scleroderma renal crisis","volume":"5","author":"Lynch","year":"2016","journal-title":"Clin Exp Rheumatol"},{"key":"2022062017050995000_47.11.1668.8","first-page":"1","article-title":"Management of renal involvement in scleroderma","volume":"8","author":"Stern","year":"2015","journal-title":"Curr Treat Options Rheumatol"},{"key":"2022062017050995000_47.11.1668.9","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1002\/art.30111","article-title":"HLA-DRB1*0407 and *1304 are risk factors for scleroderma renal crisis","volume":"63","author":"Nguyen","year":"2011","journal-title":"Arthritis Rheum"},{"key":"2022062017050995000_47.11.1668.10","doi-asserted-by":"publisher","DOI":"10.1002\/art.38098"},{"key":"2022062017050995000_47.11.1668.11","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"2022062017050995000_47.11.1668.12","unstructured":"R Development Core Team. 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