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Autoantibodies to c...
Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism
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- Wigerblad, G. (författare)
- Karolinska Institutet, Stockholm, Sweden
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- Bas, D. B. (författare)
- Karolinska Institutet, Stockholm, Sweden
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- Fernades-Cerqueira, C. (författare)
- Karolinska Institutet,Karolinska Institutet, CMM, Karolinska University Hospital Solna, Stockholm, Sweden
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visa fler...
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- Krishnamurthy, A. (författare)
- Karolinska Institutet,Karolinska Institutet, CMM, Karolinska University Hospital Solna, Stockholm, Sweden
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- Nandakumar, Kutty Selva, 1965- (författare)
- Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
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- Rogoz, K. (författare)
- Karolinska Institutet, Stockholm, Sweden
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- Kato, J. (författare)
- Karolinska Institutet, Stockholm, Sweden
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- Sandor, K. (författare)
- Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
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- Su, J. (författare)
- Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
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- Jimenez-Andrade, J. M. (författare)
- Universidad Autonoma de Tamaulipas, Reynosa, Tamaulipas, Mexico
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- Finn, A. (författare)
- Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
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- Bersellini Farinotti, A. (författare)
- Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
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- Amara, K. (författare)
- Karolinska Institutet, CMM, Karolinska University Hospital Solna, Stockholm, Sweden
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- Lundberg, K. (författare)
- Karolinska Institutet,Karolinska Institutet, CMM, Karolinska University Hospital Solna, Stockholm, Sweden
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- Holmdahl, R. (författare)
- Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
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- Jakobsson, P. J. (författare)
- Karolinska Institutet,Karolinska Institutet, CMM, Karolinska University Hospital Solna, Stockholm, Sweden
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- Malmström, V. (författare)
- Karolinska Institutet,Karolinska Institutet, CMM, Karolinska University Hospital Solna, Stockholm, Sweden
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- Catrina, A. I. (författare)
- Karolinska Institutet,Karolinska Institutet, CMM, Karolinska University Hospital Solna, Stockholm, Sweden
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- Klareskog, L. (författare)
- Karolinska Institutet, CMM, Karolinska University Hospital Solna, Stockholm, Sweden
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- Svensson, C. I. (författare)
- Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
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(creator_code:org_t)
- 2015-11-27
- 2016
- Engelska.
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:4, s. 730-738
- Relaterad länk:
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https://doi.org/10.1...
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visa fler...
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https://ard.bmj.com/...
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https://hh.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- OBJECTIVE: An 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. METHODS: Antibodies 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. RESULTS: Mice 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. CONCLUSIONS: The 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- Animals
- Arthralgia/*immunology
- Autoantibodies/*immunology/pharmacology
- Behavior
- Animal/drug effects
- Case-Control Studies
- Chemokine CXCL1/drug effects/*immunology
- Chemokines
- Citrulline/*immunology
- Inflammation
- Interleukin-8/drug effects/*immunology
- Male
- Mice
- Mice
- Inbred BALB C
- Nociception/drug effects/*physiology
- Osteoclasts/drug effects/*immunology
- Receptors
- Interleukin-8/antagonists & inhibitors
- Sulfonamides/pharmacology
- Ant-CCP
- Autoantibodies
- Fibromyalgis/Pain Syndromes
- Rheumatoid Arthritis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Wigerblad, G.
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Bas, D. B.
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Fernades-Cerquei ...
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Krishnamurthy, A ...
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Nandakumar, Kutt ...
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Rogoz, K.
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visa fler...
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Kato, J.
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Sandor, K.
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Su, J.
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Jimenez-Andrade, ...
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Finn, A.
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Bersellini Farin ...
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Amara, K.
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Lundberg, K.
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Holmdahl, R.
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Jakobsson, P. J.
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Malmström, V.
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Catrina, A. I.
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Klareskog, L.
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Svensson, C. I.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Reumatologi och ...
- Artiklar i publikationen
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Annals of the Rh ...
- Av lärosätet
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Högskolan i Halmstad
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Karolinska Institutet