Fcγ-receptor-IIIA bioactivity of circulating and synovial immune complexes in rheumatoid arthritis.

IF 5.1 2区 医学 Q1 RHEUMATOLOGY RMD Open Pub Date : 2024-08-28 DOI:10.1136/rmdopen-2024-004190
Ivana Andreeva, Philipp Kolb, Lea Rodon, Norbert Blank, Hanns-Martin Lorenz, Wolfgang Merkt
{"title":"Fcγ-receptor-IIIA bioactivity of circulating and synovial immune complexes in rheumatoid arthritis.","authors":"Ivana Andreeva, Philipp Kolb, Lea Rodon, Norbert Blank, Hanns-Martin Lorenz, Wolfgang Merkt","doi":"10.1136/rmdopen-2024-004190","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Previous technical limitations prevented the proof of Fcγ-receptor (FcγR)-activation by soluble immune complexes (sICs) in patients. FcγRIIIa (CD16) is a risk factor in rheumatoid arthritis (RA). We aimed at determining the presence of CD16-activating sICs in RA and control diseases.</p><p><strong>Methods: </strong>Sera from an exploratory cohort (n=50 patients with RA) and a validation cohort (n=106 patients with RA, 20 patients with psoriasis arthritis (PsA), 22 patients with systemic lupus erythematosus (SLE) and 31 healthy controls) were analysed using a new reporter cell assay. Additionally, 26 synovial fluid samples were analysed, including paired serum/synovial samples.</p><p><strong>Results: </strong>For the first time using a reliable and sensitive functional assay, the presence of sICs in RA sera was confirmed. sICs possess an intrinsic capacity to activate CD16 and can be found in both synovial fluid and in blood. In low experimental dilutions, circulating sICs were also detected in a subset of healthy people and in PsA. However, we report a significantly increased frequency of bioactive circulating sICs in RA. While the bioactivity of circulating sICs was low and did not correlate with clinical parameters, synovial sICs were highly bioactive and correlated with serum autoantibody levels. Receiver operator curves indicated that sICs bioactivity in synovial fluid could be used to discriminate immune complex-associated arthritis from non-associated forms. Finally, circulating sICs were more frequently found in SLE than in RA. The degree of CD16 bioactivity showed strong donor-dependent differences, especially in SLE.</p><p><strong>Conclusions: </strong>RA is characterised by the presence of circulating and synovial sICs that can engage and activate CD16.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367361/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"RMD Open","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/rmdopen-2024-004190","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

Abstract

Objective: Previous technical limitations prevented the proof of Fcγ-receptor (FcγR)-activation by soluble immune complexes (sICs) in patients. FcγRIIIa (CD16) is a risk factor in rheumatoid arthritis (RA). We aimed at determining the presence of CD16-activating sICs in RA and control diseases.

Methods: Sera from an exploratory cohort (n=50 patients with RA) and a validation cohort (n=106 patients with RA, 20 patients with psoriasis arthritis (PsA), 22 patients with systemic lupus erythematosus (SLE) and 31 healthy controls) were analysed using a new reporter cell assay. Additionally, 26 synovial fluid samples were analysed, including paired serum/synovial samples.

Results: For the first time using a reliable and sensitive functional assay, the presence of sICs in RA sera was confirmed. sICs possess an intrinsic capacity to activate CD16 and can be found in both synovial fluid and in blood. In low experimental dilutions, circulating sICs were also detected in a subset of healthy people and in PsA. However, we report a significantly increased frequency of bioactive circulating sICs in RA. While the bioactivity of circulating sICs was low and did not correlate with clinical parameters, synovial sICs were highly bioactive and correlated with serum autoantibody levels. Receiver operator curves indicated that sICs bioactivity in synovial fluid could be used to discriminate immune complex-associated arthritis from non-associated forms. Finally, circulating sICs were more frequently found in SLE than in RA. The degree of CD16 bioactivity showed strong donor-dependent differences, especially in SLE.

Conclusions: RA is characterised by the presence of circulating and synovial sICs that can engage and activate CD16.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
类风湿性关节炎循环和滑膜免疫复合物的 Fcγ 受体-IIIA 生物活性。
目的:以往的技术限制阻碍了对患者体内可溶性免疫复合物(sIC)激活 Fcγ 受体(FcγR)的证明。FcγRⅢa(CD16)是类风湿性关节炎(RA)的一个危险因素。我们的目的是确定类风湿性关节炎和对照疾病中是否存在 CD16 激活的 sIC:使用一种新的报告细胞检测法分析了来自探索性队列(50 名 RA 患者)和验证性队列(106 名 RA 患者、20 名银屑病关节炎(PsA)患者、22 名系统性红斑狼疮(SLE)患者和 31 名健康对照组)的血清。此外,还分析了 26 份滑液样本,包括配对的血清/滑液样本:首次使用可靠、灵敏的功能检测法证实了 RA 血清中存在 sICs。sICs 具有激活 CD16 的内在能力,可在滑液和血液中发现。在较低的实验稀释液中,也能在一部分健康人和 PsA 中检测到循环中的 sICs。然而,我们报告说,在 RA 中,具有生物活性的循环 sIC 的频率明显增加。虽然循环 sICs 的生物活性较低,且与临床参数无关,但滑膜 sICs 的生物活性很高,且与血清自身抗体水平相关。接收者运算曲线表明,滑液中的 sICs 生物活性可用于区分免疫复合物相关性关节炎和非相关性关节炎。最后,循环中的 sICs 在系统性红斑狼疮中比在 RA 中更常见。CD16的生物活性程度显示出强烈的供体依赖性差异,特别是在系统性红斑狼疮中:结论:RA的特征是存在可参与和激活CD16的循环和滑膜sICs。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
RMD Open
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.
期刊最新文献
Impact of patient characteristics on ASDAS disease activity state cut-offs in axial spondyloarthritis: results from nine European rheumatology registries. Association between musculoskeletal sonographic features and response to treatment in patients with psoriatic arthritis. Value of the central sensitisation inventory in patients with axial spondyloarthritis. Baseline and 2-year differences in spinal symptoms and spinal and hip mobility in early axial spondyloarthritis and non-axial spondyloarthritis chronic back pain patients. Disease response in rheumatoid arthritis across four biologic therapies associates with improvement in paraoxonase-1 activity and oxylipins.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1