ArticleAnnals of the rheumatic diseases2016
Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism.
Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04474392 (Sputum Studies of Anti-Citrullinated Protein Antibodies), which is not on this map. Cited by 145 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Sputum Studies of Anti-Citrullinated Protein Antibodies (ACPA) and Rheumatoid Arthritis (RA) Origins
Who cites it
145 citing papers in PubMed, 3 syntheses or guidelines pooled it, 251 citations in OpenAlex.
- Screening for Circulating Inflammatory Proteins Does Not Reveal Plasma Biomarkers of Constant Tinnitus.Journal of the Association for Research in Otolaryngology : JARO · 2023Pooled it
- Fc Gamma Receptors as Regulators of Bone Destruction in Inflammatory Arthritis.Frontiers in immunology · 2021Pooled it
- Effects of moxibustion on pain behaviors in patients with rheumatoid arthritis: A meta-analysis.Medicine · 2019Pooled it
- Baseline synovitis-tenosynovitis is associated with remission in early rheumatoid arthritis, but discordance with disease activity is a changeable state.Rheumatology (Oxford, England) · 2025Trial
- The Efficacy of Moxibustion on the Serum Levels of CXCL1 andPain research & managementTrial
- Inhibition of Janus kinase/signal transducer and activator of transcription reduces nociceptive sensitization in a murine model of complex regional pain syndrome.Pain reports · 2026Article
- Anti-Modified Protein Antibodies in Rheumatoid Arthritis: Pathogenic, Protective, or Passive Bystander?Immunological reviews · 2026Review
- Clinical outcomes in psoriatic arthritis patients with rheumatoid factor positivity.Rheumatology (Oxford, England) · 2026Article
- Human pain transcriptomics: lessons learned so far.Pain reports · 2026Review
- Cytotoxic CD4Signal transduction and targeted therapy · 2026Review
- Pathogenic Drivers of Difficult-to-Treat Rheumatoid Arthritis: Synovium and Beyond.International journal of molecular sciences · 2026Review
- Age-associated B-cells across the rheumatoid arthritis continuum: from early immunopathogenesis to comorbidities.Frontiers in aging · 2026Review
- Rheumatoid Arthritis: A Comprehensive Review of Etiology, Pathophysiology, and Innovative Therapeutic Advancements.Current pharmaceutical design · 2026Review
- Immunological heterogeneity in rheumatoid arthritis: challenges in early-stage stratification, non-response to targeted therapy, and the restoration of immune tolerance.Frontiers in immunology · 2026Review
- Article
- Article
- Synovial fibroblast activation occurs before the onset of rheumatoid arthritis and influences the risk of developing disease.RMD open · 2025Article
- Presence and reactivities of antibodies directed to citrullinated peptides in a Swedish JIA cohort.Pediatric rheumatology online journal · 2025Article
- Aβ low threshold mechanoreceptors contribute to sensory abnormalities in fibromyalgia.Brain : a journal of neurology · 2025Article
- Pain in systemic lupus erythematosus: emerging insights and paradigms.Nature reviews. Rheumatology · 2025Review
85 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Erratum issuedCorrection:2019
Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAn interesting and so far unexplained feature of chronic pain in autoimmune disease is the frequent disconnect between pain and inflammation. This is illustrated well in rheumatoid arthritis (RA) where pain in joints (arthralgia) may precede joint inflammation and persist even after successful anti-inflammatory treatment. In the present study, we have addressed the possibility that autoantibodies against citrullinated proteins (ACPA), present in RA, may be directly responsible for the induction of pain, independent of inflammation.
methodsAntibodies purified from human patients with RA, healthy donors and murinised monoclonal ACPA were injected into mice. Pain-like behaviour was monitored for up to 28 days, and tissues were analysed for signs of pathology. Mouse osteoclasts were cultured and stimulated with antibodies, and supernatants analysed for release of factors. Mice were treated with CXCR1/2 (interleukin (IL) 8 receptor) antagonist reparixin.
resultsMice injected with either human or murinised ACPA developed long-lasting pronounced pain-like behaviour in the absence of inflammation, while non-ACPA IgG from patients with RA or control monoclonal IgG were without pronociceptive effect. This effect was coupled to ACPA-mediated activation of osteoclasts and release of the nociceptive chemokine CXCL1 (analogue to human IL-8). ACPA-induced pain-like behaviour was reversed with reparixin.
conclusionsThe data suggest that CXCL1/IL-8, released from osteoclasts in an autoantibody-dependent manner, produces pain by activating sensory neurons. The identification of this new pain pathway may open new avenues for pain treatment in RA and also in other painful diseases associated with autoantibody production and/or osteoclast activation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.