Po-Ku Chen, Yi-Ming Chen, Chia-Fong Cho, Jeremy J J W Chen, Jian-Ching Wu, David Daf, Ning-Rong Gong, Der-Yuan Chen
{"title":"一个包含RIN3、NLRC3和SLX4基因变异的小组显示,在预测类风湿关节炎患者接受托法替尼治疗后的缓解方面有希望。","authors":"Po-Ku Chen, Yi-Ming Chen, Chia-Fong Cho, Jeremy J J W Chen, Jian-Ching Wu, David Daf, Ning-Rong Gong, Der-Yuan Chen","doi":"10.55563/clinexprheumatol/lkqekd","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To promote a treat-to-target goal of tofacitinib therapy, there are unmet needs to predict therapeutic response before treatment. Utilising whole-exome sequencing (WES) and real-time polymerase chain reaction (RT-PCR) analysis, we aim to identify predictors of achieving remission after tofacitinib therapy in rheumatoid arthritis (RA) patients.</p><p><strong>Methods: </strong>We enrolled 242 patients who had received 24-week tofacitinib therapy, including 94 patients (Cohort-1) underwent WES analysis in the discovery stage and 148 patients (Cohort-2) were validated with RT-PCR assays or Sanger sequencing in the replication stage. Disease activity was assessed using the 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), and therapeutic response at week24 was considered remission if DAS28-ESR <2.6.</p><p><strong>Results: </strong>The WES analysis identified ten variants of RIN3, NLRC3, and SLX4 genes that were predictive of achieving remission after tofacitinib therapy, and its results were completely consistent with those from TaqMan assay or Sanger sequencing. Combined variants of RIN3, NLRC3, and SLX4 genes could predict achieving remission with AUC 0.831, specificity 97.4%, and accuracy 91.5% (Cohort-1). With validation in Cohort-2, a panel incorporating genetic variants of RIN3, NLRC3, and SLX4 showed a high specificity 97.0% and accuracy 86.0%. Using multiplexed one-step RT-PCR assay, this genetic panel still predicts remission with a high specificity 97.0% and accuracy of 88.0%. The significant differences in plasma levels of NLRC3, caspase-1, and IL-6 between the mutant gene and naive gene support the results of the gene ontology analysis.</p><p><strong>Conclusions: </strong>Combined variants of RIN3, NLRC3, and SLX4 genes have great potential for predicting remission in tofacitinib-treated patients.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"1548-1553"},"PeriodicalIF":3.4000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A panel incorporating genetic variants of RIN3, NLRC3, and SLX4 shows promise in predicting remission after tofacitinib therapy in rheumatoid arthritis patients.\",\"authors\":\"Po-Ku Chen, Yi-Ming Chen, Chia-Fong Cho, Jeremy J J W Chen, Jian-Ching Wu, David Daf, Ning-Rong Gong, Der-Yuan Chen\",\"doi\":\"10.55563/clinexprheumatol/lkqekd\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>To promote a treat-to-target goal of tofacitinib therapy, there are unmet needs to predict therapeutic response before treatment. Utilising whole-exome sequencing (WES) and real-time polymerase chain reaction (RT-PCR) analysis, we aim to identify predictors of achieving remission after tofacitinib therapy in rheumatoid arthritis (RA) patients.</p><p><strong>Methods: </strong>We enrolled 242 patients who had received 24-week tofacitinib therapy, including 94 patients (Cohort-1) underwent WES analysis in the discovery stage and 148 patients (Cohort-2) were validated with RT-PCR assays or Sanger sequencing in the replication stage. Disease activity was assessed using the 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), and therapeutic response at week24 was considered remission if DAS28-ESR <2.6.</p><p><strong>Results: </strong>The WES analysis identified ten variants of RIN3, NLRC3, and SLX4 genes that were predictive of achieving remission after tofacitinib therapy, and its results were completely consistent with those from TaqMan assay or Sanger sequencing. Combined variants of RIN3, NLRC3, and SLX4 genes could predict achieving remission with AUC 0.831, specificity 97.4%, and accuracy 91.5% (Cohort-1). With validation in Cohort-2, a panel incorporating genetic variants of RIN3, NLRC3, and SLX4 showed a high specificity 97.0% and accuracy 86.0%. Using multiplexed one-step RT-PCR assay, this genetic panel still predicts remission with a high specificity 97.0% and accuracy of 88.0%. The significant differences in plasma levels of NLRC3, caspase-1, and IL-6 between the mutant gene and naive gene support the results of the gene ontology analysis.</p><p><strong>Conclusions: </strong>Combined variants of RIN3, NLRC3, and SLX4 genes have great potential for predicting remission in tofacitinib-treated patients.</p>\",\"PeriodicalId\":10274,\"journal\":{\"name\":\"Clinical and experimental rheumatology\",\"volume\":\" \",\"pages\":\"1548-1553\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and experimental rheumatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.55563/clinexprheumatol/lkqekd\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/21 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and experimental rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.55563/clinexprheumatol/lkqekd","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/21 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
A panel incorporating genetic variants of RIN3, NLRC3, and SLX4 shows promise in predicting remission after tofacitinib therapy in rheumatoid arthritis patients.
Objectives: To promote a treat-to-target goal of tofacitinib therapy, there are unmet needs to predict therapeutic response before treatment. Utilising whole-exome sequencing (WES) and real-time polymerase chain reaction (RT-PCR) analysis, we aim to identify predictors of achieving remission after tofacitinib therapy in rheumatoid arthritis (RA) patients.
Methods: We enrolled 242 patients who had received 24-week tofacitinib therapy, including 94 patients (Cohort-1) underwent WES analysis in the discovery stage and 148 patients (Cohort-2) were validated with RT-PCR assays or Sanger sequencing in the replication stage. Disease activity was assessed using the 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), and therapeutic response at week24 was considered remission if DAS28-ESR <2.6.
Results: The WES analysis identified ten variants of RIN3, NLRC3, and SLX4 genes that were predictive of achieving remission after tofacitinib therapy, and its results were completely consistent with those from TaqMan assay or Sanger sequencing. Combined variants of RIN3, NLRC3, and SLX4 genes could predict achieving remission with AUC 0.831, specificity 97.4%, and accuracy 91.5% (Cohort-1). With validation in Cohort-2, a panel incorporating genetic variants of RIN3, NLRC3, and SLX4 showed a high specificity 97.0% and accuracy 86.0%. Using multiplexed one-step RT-PCR assay, this genetic panel still predicts remission with a high specificity 97.0% and accuracy of 88.0%. The significant differences in plasma levels of NLRC3, caspase-1, and IL-6 between the mutant gene and naive gene support the results of the gene ontology analysis.
Conclusions: Combined variants of RIN3, NLRC3, and SLX4 genes have great potential for predicting remission in tofacitinib-treated patients.
期刊介绍:
Clinical and Experimental Rheumatology is a bi-monthly international peer-reviewed journal which has been covering all clinical, experimental and translational aspects of musculoskeletal, arthritic and connective tissue diseases since 1983.