类风湿关节炎一线治疗后，纤维母细胞样滑膜细胞靶向抗体与未能达到早期持续缓解或疾病活动度低有关。

IF 5.1 2区医学 Q1 RHEUMATOLOGY RMD Open Pub Date : 2024-11-17 DOI:10.1136/rmdopen-2024-004743

Patrick Vandormael, Sukayna Fadlallah, Pieter Ruytinx, Astrid Pues, Ellen Sleurs, Jori Liesenborgs, Johan Joly, Anouk Agten, Frank Vandenabeele, Judith Fraussen, Patrick Verschueren, Veerle Somers

{"title":"类风湿关节炎一线治疗后，纤维母细胞样滑膜细胞靶向抗体与未能达到早期持续缓解或疾病活动度低有关。","authors":"Patrick Vandormael, Sukayna Fadlallah, Pieter Ruytinx, Astrid Pues, Ellen Sleurs, Jori Liesenborgs, Johan Joly, Anouk Agten, Frank Vandenabeele, Judith Fraussen, Patrick Verschueren, Veerle Somers","doi":"10.1136/rmdopen-2024-004743","DOIUrl":null,"url":null,"abstract":"Objective: To discover antibody biomarkers that can predict a lack of response to first-line therapy in rheumatoid arthritis (RA) patients.Methods: Two RA cDNA phage display libraries were screened for novel antibodies in baseline RA sera from the Care in early RA (CareRA) trial, differentiating between patients who did or did not reach remission after first-line therapy (n=20 each). Antibody reactivity to identified University Hasselt (UH)-RA antigens was validated in baseline samples from 136 additional CareRA participants. The novel antibodies' potential to predict failure to reach remission or low disease activity (LDA), according to the Disease Activity Score 28-joint C-reactive protein/erythrocyte sedimentation rate (DAS28CRP/ESR) and Clinical/Simplified Disease Activity Index (CDAI/SDAI), was studied by multivariate analyses. The presence of the antibody targets in RA synovial tissue and the fibroblast-like synoviocyte (FLS) cell line SW982 was determined by immunofluorescence.Results: We identified antibodies to 41 novel antigens. Antibodies against any of three antigens, UH-RA.305/318/329, discriminated between RA patients not reaching week (w)8 DAS28CRP remission and those that did (36% vs 13%,p=0.0031). In all patients, anti-UH-RA.305/318/329 antibody reactivity was associated with failure to reach week 8 DAS28CRP and DAS28ESR remission (OR 3.63,p=0.0031; OR 2.92,p=0.016; respectively), SDAI/CDAI sustained remission (OR 5.59,p=0.039 for both) and DAS28CRP and DAS28ESR sustained LDA (OR 3.7,p=0.009; OR 2.76,p=0.042; respectively). In rheumatoid factor/anti-citrullinated protein antibody (RF/ACPA) seronegative patients, these antibodies were strongly associated with failure to achieve week 8 DAS28CRP remission (OR 17.3,p=0.0029). Anti-UH-RA.305/329 antibodies were shown to target FLS in RA synovial tissue and SW982 cells.Conclusion: We identified three antibody biomarkers that are associated with failure to achieve remission/LDA after first-line RA therapy.","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1000,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574395/pdf/","citationCount":"0","resultStr":"{\"title\":\"Fibroblast-like synoviocyte targeting antibodies are associated with failure to reach early and sustained remission or low disease activity after first-line therapy in rheumatoid arthritis.\",\"authors\":\"Patrick Vandormael, Sukayna Fadlallah, Pieter Ruytinx, Astrid Pues, Ellen Sleurs, Jori Liesenborgs, Johan Joly, Anouk Agten, Frank Vandenabeele, Judith Fraussen, Patrick Verschueren, Veerle Somers\",\"doi\":\"10.1136/rmdopen-2024-004743\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Objective: To discover antibody biomarkers that can predict a lack of response to first-line therapy in rheumatoid arthritis (RA) patients.Methods: Two RA cDNA phage display libraries were screened for novel antibodies in baseline RA sera from the Care in early RA (CareRA) trial, differentiating between patients who did or did not reach remission after first-line therapy (n=20 each). Antibody reactivity to identified University Hasselt (UH)-RA antigens was validated in baseline samples from 136 additional CareRA participants. The novel antibodies' potential to predict failure to reach remission or low disease activity (LDA), according to the Disease Activity Score 28-joint C-reactive protein/erythrocyte sedimentation rate (DAS28CRP/ESR) and Clinical/Simplified Disease Activity Index (CDAI/SDAI), was studied by multivariate analyses. The presence of the antibody targets in RA synovial tissue and the fibroblast-like synoviocyte (FLS) cell line SW982 was determined by immunofluorescence.Results: We identified antibodies to 41 novel antigens. Antibodies against any of three antigens, UH-RA.305/318/329, discriminated between RA patients not reaching week (w)8 DAS28CRP remission and those that did (36% vs 13%,p=0.0031). In all patients, anti-UH-RA.305/318/329 antibody reactivity was associated with failure to reach week 8 DAS28CRP and DAS28ESR remission (OR 3.63,p=0.0031; OR 2.92,p=0.016; respectively), SDAI/CDAI sustained remission (OR 5.59,p=0.039 for both) and DAS28CRP and DAS28ESR sustained LDA (OR 3.7,p=0.009; OR 2.76,p=0.042; respectively). In rheumatoid factor/anti-citrullinated protein antibody (RF/ACPA) seronegative patients, these antibodies were strongly associated with failure to achieve week 8 DAS28CRP remission (OR 17.3,p=0.0029). Anti-UH-RA.305/329 antibodies were shown to target FLS in RA synovial tissue and SW982 cells.Conclusion: We identified three antibody biomarkers that are associated with failure to achieve remission/LDA after first-line RA therapy.\",\"PeriodicalId\":21396,\"journal\":{\"name\":\"RMD Open\",\"volume\":\"10 4\",\"pages\":\"\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-11-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574395/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"RMD Open\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/rmdopen-2024-004743\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"RMD Open","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/rmdopen-2024-004743","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

目的发现可预测类风湿性关节炎（RA）患者对一线治疗缺乏反应的抗体生物标志物：方法：从早期RA护理（CareRA）试验的基线RA血清中筛选两个RA cDNA噬菌体展示文库中的新型抗体，区分一线治疗后达到或未达到缓解的患者（各20例）。在另外136名CareRA参与者的基线样本中，对已确定的哈瑟尔特大学（UH）-RA抗原的抗体反应性进行了验证。通过多变量分析研究了新型抗体预测缓解失败或低疾病活动性（LDA）的潜力（根据疾病活动性评分28关节C反应蛋白/红细胞沉降率（DAS28CRP/ESR）和临床/简化疾病活动性指数（CDAI/SDAI））。免疫荧光法测定了RA滑膜组织和成纤维细胞样滑膜细胞（FLS）细胞系SW982中抗体靶点的存在情况：结果：我们发现了 41 种新型抗原的抗体。抗UH-RA.305/318/329这三种抗原中任何一种的抗体都能区分未达到DAS28CRP缓解周（w）8的RA患者和达到缓解周（w）8的RA患者（36% vs 13%,p=0.0031）。在所有患者中，抗UH-RA.305/318/329抗体反应性与第8周DAS28CRP和DAS28ESR缓解失败（OR 3.63，p=0.0031；OR 2.92，p=0.016；分别）、SDAI/CDAI持续缓解（OR 5.59，两者p=0.039）以及DAS28CRP和DAS28ESR持续LDA（OR 3.7，p=0.009；OR 2.76，p=0.042；分别）相关。在类风湿因子/抗瓜氨酸蛋白抗体（RF/ACPA）血清阴性患者中，这些抗体与第 8 周 DAS28CRP 缓解失败密切相关（OR 17.3，p=0.0029）。抗UH-RA.305/329抗体可靶向RA滑膜组织和SW982细胞中的FLS：我们发现了三种抗体生物标志物，它们与一线RA治疗后未能达到缓解/LDA有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

Fibroblast-like synoviocyte targeting antibodies are associated with failure to reach early and sustained remission or low disease activity after first-line therapy in rheumatoid arthritis.

Objective: To discover antibody biomarkers that can predict a lack of response to first-line therapy in rheumatoid arthritis (RA) patients.

Methods: Two RA cDNA phage display libraries were screened for novel antibodies in baseline RA sera from the Care in early RA (CareRA) trial, differentiating between patients who did or did not reach remission after first-line therapy (n=20 each). Antibody reactivity to identified University Hasselt (UH)-RA antigens was validated in baseline samples from 136 additional CareRA participants. The novel antibodies' potential to predict failure to reach remission or low disease activity (LDA), according to the Disease Activity Score 28-joint C-reactive protein/erythrocyte sedimentation rate (DAS28CRP/ESR) and Clinical/Simplified Disease Activity Index (CDAI/SDAI), was studied by multivariate analyses. The presence of the antibody targets in RA synovial tissue and the fibroblast-like synoviocyte (FLS) cell line SW982 was determined by immunofluorescence.

Results: We identified antibodies to 41 novel antigens. Antibodies against any of three antigens, UH-RA.305/318/329, discriminated between RA patients not reaching week (w)8 DAS28CRP remission and those that did (36% vs 13%,p=0.0031). In all patients, anti-UH-RA.305/318/329 antibody reactivity was associated with failure to reach week 8 DAS28CRP and DAS28ESR remission (OR 3.63,p=0.0031; OR 2.92,p=0.016; respectively), SDAI/CDAI sustained remission (OR 5.59,p=0.039 for both) and DAS28CRP and DAS28ESR sustained LDA (OR 3.7,p=0.009; OR 2.76,p=0.042; respectively). In rheumatoid factor/anti-citrullinated protein antibody (RF/ACPA) seronegative patients, these antibodies were strongly associated with failure to achieve week 8 DAS28CRP remission (OR 17.3,p=0.0029). Anti-UH-RA.305/329 antibodies were shown to target FLS in RA synovial tissue and SW982 cells.

Conclusion: We identified three antibody biomarkers that are associated with failure to achieve remission/LDA after first-line RA therapy.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

RMD Open RHEUMATOLOGY-

CiteScore

7.30

自引率

6.50%

发文量

205

审稿时长

14 weeks

期刊介绍： RMD Open publishes high quality peer-reviewed original research covering the full spectrum of musculoskeletal disorders, rheumatism and connective tissue diseases, including osteoporosis, spine and rehabilitation. Clinical and epidemiological research, basic and translational medicine, interesting clinical cases, and smaller studies that add to the literature are all considered.