CoChat
Sign Up
Cited by 104Pain Mechanisms and TreatmentsIon Channels and ReceptorsRheumatoid Arthritis Research and Therapies

Cartilage-binding antibodies induce pain through immune complex–mediated activation of neurons

Open access
Bersellini Farinotti, Alex, Wigerblad, Gustaf, Nascimento, Diana, Bas, Duygu B., Morado Urbina, Carlos, Nandakumar, Kutty Selva, Sandor, Katalin, Xu, Bingze +23 more·2019·Journal of Experimental Medicine
DOI 10.1084/jem.20181657PMC PMC6683987
Open this paper in CoChat — free accountOpen PDF

Abstract

Rheumatoid arthritis–associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications of inflammation. Cartilage antibody–induced pain-like behavior does not depend on complement activation or joint inflammation, but instead on tissue antigen recognition and local immune complex (IC) formation. smFISH and IHC suggest that neuronal Fcgr1 and Fcgr2b mRNA are transported to peripheral ends of primary afferents. CII-ICs directly activate cultured WT but not FcRγ chain–deficient DRG neurons. In line with this observation, CII-IC does not induce mechanical hypersensitivity in FcRγ chain–deficient mice. Furthermore, injection of CII antibodies does not generate pain-like behavior in FcRγ chain–deficient mice or mice lacking activating FcγRs in neurons. In summary, this study defines functional coupling between autoantibodies and pain transmission that may facilitate the development of new disease-relevant pain therapeutics.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1084/jem.20181657

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 58

  1. Agalave N.M., Larsson M., Abdelmoaty S., Su J., Baharpoor A., Lundbäck P., Palmblad K., Andersson U., Harris H., and Svensson C.I. 2014 Spinal HMGB1 induces TLR4-mediated long-lasting hypersensitivity and glial activation and regulates pain-like behavior in experimental arthritis. Pain. 155: 1802– 1813. 10.1016/j.pain.2014.06.007 24954167 · DOI
  2. Amirahmadi S.F., Whittingham S., Crombie D.E., Nandakumar K.S., Holmdahl R., Mackay I.R., van Damme M.P., and Rowley M.J. 2005 Arthritogenic anti-type II collagen antibodies are pathogenic for cartilage-derived chondrocytes independent of inflammatory cells. Arthritis Rheum. 52: 1897– 1906. 10.1002/art.21097 15934095 · DOI
  3. Andoh T., and Kuraishi Y. 2004 Direct action of immunoglobulin G on primary sensory neurons through Fc gamma receptor I. FASEB J. 18: 182– 184. 10.1096/fj.02-1169fje 14630707 · DOI
  4. Bas D.B., Su J., Sandor K., Agalave N.M., Lundberg J., Codeluppi S., Baharpoor A., Nandakumar K.S., Holmdahl R., and Svensson C.I. 2012 Collagen antibody-induced arthritis evokes persistent pain with spinal glial involvement and transient prostaglandin dependency. Arthritis Rheum. 64: 3886– 3896. 10.1002/art.37686 22933386 · DOI
  5. Boyle D.L., Rosengren S., Bugbee W., Kavanaugh A., and Firestein G.S. 2003 Quantitative biomarker analysis of synovial gene expression by real-time PCR. Arthritis Res. Ther. 5: R352– R360. 10.1186/ar1004 14680510 PMC333415 · DOI
  6. Burkhardt H., Koller T., Engström A., Nandakumar K.S., Turnay J., Kraetsch H.G., Kalden J.R., and Holmdahl R. 2002 Epitope-specific recognition of type II collagen by rheumatoid arthritis antibodies is shared with recognition by antibodies that are arthritogenic in collagen-induced arthritis in the mouse. Arthritis Rheum. 46: 2339– 2348. 10.1002/art.10472 12355481 · DOI
  7. Chaplan S.R., Bach F.W., Pogrel J.W., Chung J.M., and Yaksh T.L. 1994 Quantitative assessment of tactile allodynia in the rat paw. J. Neurosci. Methods. 53: 55– 63. 10.1016/0165-0270(94)90144-9 7990513 · DOI
  8. Cho H., Jang Y., Lee B., Chun H., Jung J., Kim S.M., Hwang S.W., and Oh U. 2013 Voluntary movements as a possible non-reflexive pain assay. Mol. Pain. 9: 25 10.1186/1744-8069-9-25 23688027 PMC3716716 · DOI
  9. Clague R.B., and Moore L.J. 1984 IgG and IgM antibody to native type II collagen in rheumatoid arthritis serum and synovial fluid. Evidence for the presence of collagen-anticollagen immune complexes in synovial fluid. Arthritis Rheum. 27: 1370– 1377. 10.1002/art.1780271207 6095870 · DOI
  10. Codeluppi S., Borm L.E., Zeisel A., La Manno G., van Lunteren J.A., Svensson C.I., and Linnarsson S. 2018 Spatial organization of the somatosensory cortex revealed by osmFISH. Nat. Methods. 15: 932– 935. 10.1038/s41592-018-0175-z 30377364 · DOI
  11. Collin M., and Olsén A. 2001 EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG. EMBO J. 20: 3046– 3055. 10.1093/emboj/20.12.3046 11406581 PMC150189 · DOI
  12. Croxford A.M., Crombie D., McNaughton D., Holmdahl R., Nandakumar K.S., and Rowley M.J. 2010 Specific antibody protection of the extracellular cartilage matrix against collagen antibody-induced damage. Arthritis Rheum. 62: 3374– 3384. 10.1002/art.27671 20662051 · DOI
  13. Dawes J.M., Weir G.A., Middleton S.J., Patel R., Chisholm K.I., Pettingill P., Peck L.J., Sheridan J., Shakir A., Jacobson L., 2018 Immune or Genetic-Mediated Disruption of CASPR2 Causes Pain Hypersensitivity Due to Enhanced Primary Afferent Excitability. Neuron. 97: 806– 822.e10. 10.1016/j.neuron.2018.01.033 29429934 PMC6011627 · DOI
  14. de Hair M.J., van de Sande M.G., Ramwadhdoebe T.H., Hansson M., Landewé R., van der Leij C., Maas M., Serre G., van Schaardenburg D., Klareskog L., 2014 Features of the synovium of individuals at risk of developing rheumatoid arthritis: implications for understanding preclinical rheumatoid arthritis. Arthritis Rheumatol. 66: 513– 522. 10.1002/art.38273 24574210 PMC4034588 · DOI
  15. Eyre D.R. 1991 The collagens of articular cartilage. Semin. Arthritis Rheum. 21(3, Suppl 2): 2– 11. 10.1016/0049-0172(91)90035-X 1796302 · DOI
  16. Galligan C.L., and Fish E.N. 2012 Circulating fibrocytes contribute to the pathogenesis of collagen antibody-induced arthritis. Arthritis Rheum. 64: 3583– 3593. 10.1002/art.34589 22729466 · DOI
  17. Geng H., Nandakumar K.S., Pramhed A., Aspberg A., Mattsson R., and Holmdahl R. 2012 Cartilage oligomeric matrix protein specific antibodies are pathogenic. Arthritis Res. Ther. 14: R191 10.1186/ar4022 22906101 PMC3580587 · DOI
  18. Haag S., Schneider N., Mason D.E., Tuncel J., Andersson I.E., Peters E.C., Burkhardt H., and Holmdahl R. 2014 Identification of new citrulline-specific autoantibodies, which bind to human arthritic cartilage, by mass spectrometric analysis of citrullinated type II collagen. Arthritis Rheumatol. 66: 1440– 1449. 10.1002/art.38383 24470447 · DOI
  19. Hazenbos W.L., Gessner J.E., Hofhuis F.M., Kuipers H., Meyer D., Heijnen I.A., Schmidt R.E., Sandor M., Capel P.J., Daëron M., 1996 Impaired IgG-dependent anaphylaxis and Arthus reaction in Fc gamma RIII (CD16) deficient mice. Immunity. 5: 181– 188. 10.1016/S1074-7613(00)80494-X 8769481 · DOI
  20. Holmdahl R., Rubin K., Klareskog L., Larsson E., and Wigzell H. 1986 Characterization of the antibody response in mice with type II collagen-induced arthritis, using monoclonal anti-type II collagen antibodies. Arthritis Rheum. 29: 400– 410. 10.1002/art.1780290314 2421741 · DOI
  21. Holmdahl R., Carlsen S., Mikulowska A., Vestberg M., Brunsberg U., Hansson A.-S., Sundvall M., Jansson L., and Pettersson U. 1998 Genetic analysis of mouse models for rheumatoid arthritis. In Human Genome Methods. CRC Press, Boca Raton, FL pp. 215– 238.
  22. Jiang H., Shen X., Chen Z., Liu F., Wang T., Xie Y., and Ma C. 2017 Nociceptive neuronal Fc-gamma receptor I is involved in IgG immune complex induced pain in the rat. Brain Behav. Immun. 62: 351– 361. 10.1016/j.bbi.2017.03.001 28263785 · DOI
  23. Jiménez-Díaz L., Géranton S.M., Passmore G.M., Leith J.L., Fisher A.S., Berliocchi L., Sivasubramaniam A.K., Sheasby A., Lumb B.M., and Hunt S.P. 2008 Local translation in primary afferent fibers regulates nociception. PLoS One. 3: e1961 10.1371/journal.pone.0001961 18398477 PMC2276314 · DOI
  24. Johansson A.C., Sundler M., Kjellén P., Johannesson M., Cook A., Lindqvist A.K., Nakken B., Bolstad A.I., Jonsson R., Alarcón-Riquelme M., and Holmdahl R. 2001 Genetic control of collagen-induced arthritis in a cross with NOD and C57BL/10 mice is dependent on gene regions encoding complement factor 5 and FcgammaRIIb and is not associated with loci controlling diabetes. Eur. J. Immunol. 31: 1847– 1856. 10.1002/1521-4141(200106)31:6<1847::AID-IMMU1847>3.0.CO;2-F 11433381 · DOI
  25. Jonsson R., Karlsson A.L., and Holmdahl R. 1989 Demonstration of immunoreactive sites on cartilage after in vivo administration of biotinylated anti-type II collagen antibodies. J. Histochem. Cytochem. 37: 265– 268. 10.1177/37.2.2911008 2911008 · DOI
  26. Klein C.J., Lennon V.A., Aston P.A., McKeon A., and Pittock S.J. 2012 Chronic pain as a manifestation of potassium channel-complex autoimmunity. Neurology. 79: 1136– 1144. 10.1212/WNL.0b013e3182698cab 22895588 PMC3525306 · DOI
  27. Li C., and Wong W.H. 2001 Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc. Natl. Acad. Sci. USA. 98: 31– 36. 10.1073/pnas.98.1.31 11134512 PMC14539 · DOI · Paper page
  28. Lindh I., Snir O., Lönnblom E., Uysal H., Andersson I., Nandakumar K.S., Vierboom M., ’t Hart B., Malmström V., and Holmdahl R. 2014 Type II collagen antibody response is enriched in the synovial fluid of rheumatoid joints and directed to the same major epitopes as in collagen induced arthritis in primates and mice. Arthritis Res. Ther. 16: R143 10.1186/ar4605 25005029 PMC4226996 · DOI
  29. Lohmander L.S., Atley L.M., Pietka T.A., and Eyre D.R. 2003 The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis. Arthritis Rheum. 48: 3130– 3139. 10.1002/art.11326 14613275 · DOI
  30. Mantyh P.W., Koltzenburg M., Mendell L.M., Tive L., and Shelton D.L. 2011 Antagonism of nerve growth factor-TrkA signaling and the relief of pain. Anesthesiology. 115: 189– 204. 10.1097/ALN.0b013e31821b1ac5 21602663 PMC3121917 · DOI
  31. Mohamed H.A., Mosier D.R., Zou L.L., Siklós L., Alexianu M.E., Engelhardt J.I., Beers D.R., Le W.D., and Appel S.H. 2002 Immunoglobulin Fc gamma receptor promotes immunoglobulin uptake, immunoglobulin-mediated calcium increase, and neurotransmitter release in motor neurons. J. Neurosci. Res. 69: 110– 116. 10.1002/jnr.10271 12111822 · DOI
  32. Nandakumar K.S., and Holmdahl R. 2005 Efficient promotion of collagen antibody induced arthritis (CAIA) using four monoclonal antibodies specific for the major epitopes recognized in both collagen induced arthritis and rheumatoid arthritis. J. Immunol. Methods. 304: 126– 136. 10.1016/j.jim.2005.06.017 16125192 · DOI
  33. Nandakumar K.S., Svensson L., and Holmdahl R. 2003 Collagen type II-specific monoclonal antibody-induced arthritis in mice: description of the disease and the influence of age, sex, and genes. Am. J. Pathol. 163: 1827– 1837. 10.1016/S0002-9440(10)63542-0 14578183 PMC1892447 · DOI
  34. Nandakumar K.S., Collin M., Olsén A., Nimmerjahn F., Blom A.M., Ravetch J.V., and Holmdahl R. 2007 Endoglycosidase treatment abrogates IgG arthritogenicity: importance of IgG glycosylation in arthritis. Eur. J. Immunol. 37: 2973– 2982. 10.1002/eji.200737581 17899548 · DOI
  35. Nandakumar K.S., Bajtner E., Hill L., Böhm B., Rowley M.J., Burkhardt H., and Holmdahl R. 2008 Arthritogenic antibodies specific for a major type II collagen triple-helical epitope bind and destabilize cartilage independent of inflammation. Arthritis Rheum. 58: 184– 196. 10.1002/art.23049 18163493 · DOI
  36. Nandakumar K.S., Collin M., Happonen K.E., Lundström S.L., Croxford A.M., Xu B., Zubarev R.A., Rowley M.J., Blom A.M., Kjellman C., and Holmdahl R. 2018 Streptococcal Endo-β-N-Acetylglucosaminidase Suppresses Antibody-Mediated Inflammation In Vivo. Front. Immunol. 9: 1623 10.3389/fimmu.2018.01623 30061892 PMC6054937 · DOI
  37. Nimmerjahn F., Bruhns P., Horiuchi K., and Ravetch J.V. 2005 FcgammaRIV: a novel FcR with distinct IgG subclass specificity. Immunity. 23: 41– 51. 10.1016/j.immuni.2005.05.010 16039578 · DOI
  38. Nimmerjahn F., Lux A., Albert H., Woigk M., Lehmann C., Dudziak D., Smith P., and Ravetch J.V. 2010 FcγRIV deletion reveals its central role for IgG2a and IgG2b activity in vivo. Proc. Natl. Acad. Sci. USA. 107: 19396– 19401. 10.1073/pnas.1014515107 20974962 PMC2984189 · DOI
  39. Obara I., Géranton S.M., and Hunt S.P. 2012 Axonal protein synthesis: a potential target for pain relief? Curr. Opin. Pharmacol. 12: 42– 48. 10.1016/j.coph.2011.10.005 22033338 · DOI
  40. Pereira R.S., Black C.M., Duance V.C., Jones V.E., Jacoby R.K., and Welsh K.I. 1985 Disappearing collagen antibodies in rheumatoid arthritis. Lancet. 2: 501– 502. 10.1016/S0140-6736(85)90436-2 2863522 · DOI
  41. Price T.J., and Géranton S.M. 2009 Translating nociceptor sensitivity: the role of axonal protein synthesis in nociceptor physiology. Eur. J. Neurosci. 29: 2253– 2263. 10.1111/j.1460-9568.2009.06786.x 19490023 PMC2914561 · DOI
  42. Qu L., Zhang P., LaMotte R.H., and Ma C. 2011 Neuronal Fc-gamma receptor I mediated excitatory effects of IgG immune complex on rat dorsal root ganglion neurons. Brain Behav. Immun. 25: 1399– 1407. 10.1016/j.bbi.2011.04.008 21521651 PMC3150223 · DOI
  43. Qu L., Li Y., Pan X., Zhang P., LaMotte R.H., and Ma C. 2012 Transient receptor potential canonical 3 (TRPC3) is required for IgG immune complex-induced excitation of the rat dorsal root ganglion neurons. J. Neurosci. 32: 9554– 9562. 10.1523/JNEUROSCI.6355-11.2012 22787041 PMC3437229 · DOI
  44. Rantapää-Dahlqvist S., de Jong B.A., Berglin E., Hallmans G., Wadell G., Stenlund H., Sundin U., and van Venrooij W.J. 2003 Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 48: 2741– 2749. 10.1002/art.11223 14558078 · DOI
  45. Raposo B., Merky P., Lundqvist C., Yamada H., Urbonaviciute V., Niaudet C., Viljanen J., Kihlberg J., Kyewski B., Ekwall O., 2018 T cells specific for post-translational modifications escape intrathymic tolerance induction. Nat. Commun. 9: 353 10.1038/s41467-017-02763-y 29367624 PMC5783942 · DOI
  46. Ray P., Torck A., Quigley L., Wangzhou A., Neiman M., Rao C., Lam T., Kim J.Y., Kim T.H., Zhang M.Q., 2018 Comparative transcriptome profiling of the human and mouse dorsal root ganglia: an RNA-seq-based resource for pain and sensory neuroscience research. Pain. 159: 1325– 1345. 10.1097/j.pain.0000000000001217 29561359 PMC6008200 · DOI
  47. Rowley M.J., Williamson D.J., and Mackay I.R. 1987 Evidence for local synthesis of antibodies to denatured collagen in the synovium in rheumatoid arthritis. Arthritis Rheum. 30: 1420– 1425. 10.1002/art.1780301215 3435570 · DOI
  48. Saxne T., and Heinegård D. 1992 Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in synovial fluid and blood. Br. J. Rheumatol. 31: 583– 591. 10.1093/rheumatology/31.9.583 1381980 · DOI
  49. Su J., Gao T., Shi T., Xiang Q., Xu X., Wiesenfeld-Hallin Z., Hökfelt T., and Svensson C.I. 2015 Phenotypic changes in dorsal root ganglion and spinal cord in the collagen antibody-induced arthritis mouse model. J. Comp. Neurol. 523: 1505– 1528. 10.1002/cne.23749 25631752 · DOI
  50. Takai T., Li M., Sylvestre D., Clynes R., and Ravetch J.V. 1994 FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell. 76: 519– 529. 10.1016/0092-8674(94)90115-5 8313472 · DOI
  51. Taylor P., Manger B., Alvaro-Gracia J., Johnstone R., Gomez-Reino J., Eberhardt E., Wolfe F., Schwartzman S., Furfaro N., and Kavanaugh A. 2010 Patient perceptions concerning pain management in the treatment of rheumatoid arthritis. J. Int. Med. Res. 38: 1213– 1224. 10.1177/147323001003800402 20925993 · DOI
  52. Terato K., Hasty K.A., Reife R.A., Cremer M.A., Kang A.H., and Stuart J.M. 1992 Induction of arthritis with monoclonal antibodies to collagen. J. Immunol. 148: 2103– 2108. 1545120
  53. Tutt A.L., James S., Laversin S.A., Tipton T.R., Ashton-Key M., French R.R., Hussain K., Vaughan A.T., Dou L., Earley A., 2015 Development and Characterization of Monoclonal Antibodies Specific for Mouse and Human Fcγ Receptors. J. Immunol. 195: 5503– 5516. 10.4049/jimmunol.1402988 26512139 · DOI
  54. van Rossum D., Hanisch U.K., and Quirion R. 1997 Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci. Biobehav. Rev. 21: 649– 678. 10.1016/S0149-7634(96)00023-1 9353797 · DOI
  55. Wigerblad G., Bas D.B., Fernades-Cerqueira C., Krishnamurthy A., Nandakumar K.S., Rogoz K., Kato J., Sandor K., Su J., Jimenez-Andrade J.M., 2016 Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann. Rheum. Dis. 75: 730– 738. 10.1136/annrheumdis-2015-208094 26613766 PMC4819624 · DOI
  56. Wiśniewski J.R. 2016 Quantitative Evaluation of Filter Aided Sample Preparation (FASP) and Multienzyme Digestion FASP Protocols. Anal. Chem. 88: 5438– 5443. 10.1021/acs.analchem.6b00859 27119963 · DOI
  57. Wiśniewski J.R., Zougman A., Nagaraj N., and Mann M. 2009 Universal sample preparation method for proteome analysis. Nat. Methods. 6: 359– 362. 10.1038/nmeth.1322 19377485 · DOI · Paper page
  58. Yoshida M., Tsuji M., Kurosaka D., Kurosaka D., Yasuda J., Ito Y., Nishizawa T., and Yamada A. 2006 Autoimmunity to citrullinated type II collagen in rheumatoid arthritis. Mod. Rheumatol. 16: 276– 281. 10.3109/s10165-006-0498-y 17039307 PMC2780673 · DOI

Cited by

Sorted by citations

Authors
Bersellini Farinotti, A., Wigerblad, G., Nascimento, D., Bas, D. B., Morado Urbina, C., Nandakumar, K. S., Sandor, K., Xu, B., Abdelmoaty, S., Hunt, M. A., Ängeby Möller, K., Baharpoor, A., Sinclair, J., Jardemark, K., Lanner, J. T., Khmaladze, I., Borm, L. E., Zhang, L., Wermeling, F., Cragg, M. S., Lengqvist, J., Chabot-Doré, A.-J., Diatchenko, L., Belfer, I., Collin, M., Kultima, K., Heyman, B., Jimenez-Andrade, J. M., Codeluppi, S., Holmdahl, R., & Svensson, C. I.
Affiliations
  • Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden 1
  • Karolinska Institutet (SE)
  • Uppsala University (SE)
  • Karolinska University Hospital (SE)
  • Southampton General Hospital (GB)
  • Alan Edwards Centre for Research on Pain, McGill University, Montréal, Quebec, Canada 8
  • McGill University (CA)
  • National Institutes of Health (US)
  • Lund University (SE)
  • Department of Unidad Academica Multidisciplinaria Reynosa Aztlan, Universidad Autonoma de Tamaulipas, Reynosa, Tamaulipas, Mexico 12
Corresponding author
  • Holmdahl, Rikard
  • Svensson, Camilla I.
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2019-06-13
Volume
216
Issue
8
Pages
1904-1924
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20181657
PMC
PMC6683987
OpenAlex
W2997764258
Cited by
104
References
0
Citations by year
2026: 11 · 2025: 14 · 2024: 13 · 2023: 10 · 2022: 13 · 2021: 17 · 2020: 17 · 2019: 9
FWCI
9.60
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • arXiv (Cornell University) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion, other-oa)
  • Diva portal (Dalarna University Library) (submittedVersion, other-oa)
  • Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
  • arXiv (Cornell University)
Funders
  • Swedish Research Council
  • Swedish Foundation for Strategic Research
  • Knut och Alice Wallenberg Foundation
  • Ragnar Söderberg Foundation
  • Torsten Söderberg Foundation
  • Åke Wiberg Foundation
  • Alfred Österlund Foundation
  • Gyllenstierna-Krapperup Foundation
  • Konung Gustaf V’s 80-year foundation
  • Swedish Arthritis Association
  • Hansa Medical AB
  • Royal Physiographic Society
  • Karolinska Institutet
  • Canadian Institutes of Health Research (G237818/CERC09/CIHR)
  • Government of Guangdong Province (201001Y04675344)
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Keywords
rheumatoid arthritis, joint pain, type II collagen, cartilage oligomeric matrix protein, immune complexes, mechanical hypersensitivity, Fc gamma receptor, FcRγ chain, dorsal root ganglion neurons, autoantibodies, pain transmission, Fc gamma receptor IIb
MeSH terms
Animals, Antibodies, Monoclonal, Antigen-Antibody Complex, Arthritis, Rheumatoid, Autoantibodies, Behavior, Animal, Cartilage, Disease Models, Animal, Female, Male, Mice, Inbred BALB C, Mice, Inbred CBA, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Receptors, IgG, Arthralgia, Collagen Type II, Mice, Cartilage Oligomeric Matrix Protein

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review