Pub Date : 2026-02-04DOI: 10.1186/s13075-026-03744-7
Olivia Solomon, Caroline Shiboski, Kimberly E Taylor, Hong Quach, Diana Quach, Lisa F Barcellos, Lindsey A Criswell
{"title":"Sjögren's patient subgroups identified through whole genome DNA methylation profiling.","authors":"Olivia Solomon, Caroline Shiboski, Kimberly E Taylor, Hong Quach, Diana Quach, Lisa F Barcellos, Lindsey A Criswell","doi":"10.1186/s13075-026-03744-7","DOIUrl":"10.1186/s13075-026-03744-7","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":"41"},"PeriodicalIF":4.6,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12896019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reassessing the role of watchful waiting strategy for IgG4-related disease: a real-world study.","authors":"Chengqian Liao, Yanli Huang, Guilian Shang, Wei Sun, Shaozhe Cai, Lingli Dong","doi":"10.1186/s13075-026-03743-8","DOIUrl":"10.1186/s13075-026-03743-8","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12924568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-28DOI: 10.1186/s13075-026-03750-9
Mario Navarrete, Khushali Trivedi, Clarissa Klenke, Zihao Zheng, Jun Kim, Jeba Atkia Maisha, Alina Semenenko, Xiaobo Meng, Obinna I Okeke, Carolina Munoz-Grajales, Christine Peschken, Miriam A Shelef, Hani S El-Gabalawy, Liam J O'Neil
Objectives: Citrullination is a post-translational modification that serves as an autoantigen in Rheumatoid Arthritis (RA). It remains unclear whether there is an excess production of specific citrullinated proteins in RA patients that is driving the autoantibody response. The aim of this study was to undertake an unsupervised proteomic analysis of the circulating RA citrullinome, and determine the consequences of citrullination in RA.
Methods: Citrullinated serum proteins were isolated and measured by mass spectrometry from 10 anti-citrullinated protein antibody (ACPA) positive RA patients and 10 controls. Cit-proteins and cit-immune complexes (IC) were measured in a larger cohort of unaffected first-degree relatives (FDR, ACPA- n = 31, ACPA+ n = 26) and RA (n = 31). Autoantibodies to citrullinated C9, and linear peptides of citrullinated C9 were measured. Structural changes imparted by citrullination were studied in-silico using Alphafold 3.0.
Results: Differential analysis of the RA citrullinome revealed a higher expression of complement proteins. Validation studies revealed that the levels of cit-C9 (p = 0.02) and cit-CFI (Complement Factor I, p = 0.019) were higher in RA than controls. Cit-C9 IgG, but not cit-CFI, immune complexes were elevated in ACPA+ FDR (p < 0.0001) and RA (p < 0.0001) compared to ACPA- FDR. Autoantibodies to cit-C9 were also higher in ACPA+ FDR (p = 0.01) and RA (p = 0.002). Reactivity to linear peptides of cit/homocit C9 were enriched in RA patients compared to controls. In-silico modelling revealed structural changes to the monomeric and multimeric structure of cit-C9.
Conclusion: This analysis of the circulating citrullinome in RA reveals the generation of citrullinated complement proteins that serve as autoantigens.
目的：瓜氨酸化是一种翻译后修饰，可作为类风湿关节炎（RA）的自身抗原。目前尚不清楚RA患者体内是否有过量的特定瓜氨酸化蛋白产生，从而驱动自身抗体反应。本研究的目的是对循环的RA瓜氨酸组进行无监督的蛋白质组学分析，并确定瓜氨酸化在RA中的后果。方法：分离10例抗瓜氨酸蛋白抗体（ACPA）阳性RA患者和10例对照组的瓜氨酸化血清蛋白，采用质谱法测定其蛋白含量。在未受影响的一级亲属（FDR, ACPA- n = 31, ACPA+ n = 26）和RA （n = 31）的更大队列中测量cit蛋白和cit免疫复合物（IC）。检测瓜氨酸化C9的自身抗体和瓜氨酸化C9的线性肽。用Alphafold 3.0在计算机上研究瓜氨酸化引起的结构变化。结果：RA瓜氨酸组的差异分析显示补体蛋白的表达较高。验证研究显示，RA患者cit-C9 （p = 0.02）和cit-CFI（补体因子I， p = 0.019）水平高于对照组。ACPA+ FDR的免疫复合物Cit-C9 IgG升高，而cit-CFI没有升高(p)。结论：对RA循环瓜氨酸组的分析揭示了作为自身抗原的瓜氨酸化补体蛋白的产生。
{"title":"The rheumatoid arthritis citrullinome is enriched in antigenic complement proteins.","authors":"Mario Navarrete, Khushali Trivedi, Clarissa Klenke, Zihao Zheng, Jun Kim, Jeba Atkia Maisha, Alina Semenenko, Xiaobo Meng, Obinna I Okeke, Carolina Munoz-Grajales, Christine Peschken, Miriam A Shelef, Hani S El-Gabalawy, Liam J O'Neil","doi":"10.1186/s13075-026-03750-9","DOIUrl":"10.1186/s13075-026-03750-9","url":null,"abstract":"<p><strong>Objectives: </strong>Citrullination is a post-translational modification that serves as an autoantigen in Rheumatoid Arthritis (RA). It remains unclear whether there is an excess production of specific citrullinated proteins in RA patients that is driving the autoantibody response. The aim of this study was to undertake an unsupervised proteomic analysis of the circulating RA citrullinome, and determine the consequences of citrullination in RA.</p><p><strong>Methods: </strong>Citrullinated serum proteins were isolated and measured by mass spectrometry from 10 anti-citrullinated protein antibody (ACPA) positive RA patients and 10 controls. Cit-proteins and cit-immune complexes (IC) were measured in a larger cohort of unaffected first-degree relatives (FDR, ACPA- n = 31, ACPA+ n = 26) and RA (n = 31). Autoantibodies to citrullinated C9, and linear peptides of citrullinated C9 were measured. Structural changes imparted by citrullination were studied in-silico using Alphafold 3.0.</p><p><strong>Results: </strong>Differential analysis of the RA citrullinome revealed a higher expression of complement proteins. Validation studies revealed that the levels of cit-C9 (p = 0.02) and cit-CFI (Complement Factor I, p = 0.019) were higher in RA than controls. Cit-C9 IgG, but not cit-CFI, immune complexes were elevated in ACPA+ FDR (p < 0.0001) and RA (p < 0.0001) compared to ACPA- FDR. Autoantibodies to cit-C9 were also higher in ACPA+ FDR (p = 0.01) and RA (p = 0.002). Reactivity to linear peptides of cit/homocit C9 were enriched in RA patients compared to controls. In-silico modelling revealed structural changes to the monomeric and multimeric structure of cit-C9.</p><p><strong>Conclusion: </strong>This analysis of the circulating citrullinome in RA reveals the generation of citrullinated complement proteins that serve as autoantigens.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12924597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27DOI: 10.1186/s13075-026-03742-9
Monica T Hannani, Jaume Bacardit, Jonathan Larkin, Virpi Glumoff, Morten A Karsdal, Anne-Christine Bay-Jensen, Ali Mobasheri, Christian S Thudium
{"title":"Cytokine profiling of molecular endotypes of knee osteoarthritis: insights from the IMI-APPROACH cohort.","authors":"Monica T Hannani, Jaume Bacardit, Jonathan Larkin, Virpi Glumoff, Morten A Karsdal, Anne-Christine Bay-Jensen, Ali Mobasheri, Christian S Thudium","doi":"10.1186/s13075-026-03742-9","DOIUrl":"10.1186/s13075-026-03742-9","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":"52"},"PeriodicalIF":4.6,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12918155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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