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Sökning: WFRF:(Anca Catrina I.) > (2015-2019) > Recognition of Amin...

  • Steen, JohannaKarolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden. (författare)

Recognition of Amino Acid Motifs, Rather Than Specific Proteins, by Human Plasma Cell-Derived Monoclonal Antibodies to Posttranslationally Modified Proteins in Rheumatoid Arthritis

  • Artikel/kapitelEngelska2019

Förlag, utgivningsår, omfång ...

  • 2019-01-29
  • WILEY,2019
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-377676
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-377676URI
  • https://doi.org/10.1002/art.40699DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-244539URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:140179914URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • QC 20190404
  • Objective: Antibodies against posttranslationally modified proteins are a hallmark of rheumatoid arthritis (RA), but the emergence and pathogenicity of these autoantibodies are still incompletely understood. The aim of this study was to analyze the antigen specificities and mutation patterns of monoclonal antibodies (mAb) derived from RA synovial plasma cells and address the question of antigen cross-reactivity.Methods: IgG-secreting cells were isolated from RA synovial fluid, and the variable regions of the immunoglobulins were sequenced (n = 182) and expressed in full-length mAb (n = 93) and also as germline-reverted versions. The patterns of reactivity with 53,019 citrullinated peptides and 49,211 carbamylated peptides and the potential of the mAb to promote osteoclastogenesis were investigated.Results: Four unrelated anti-citrullinated protein autoantibodies (ACPAs), of which one was clonally expanded, were identified and found to be highly somatically mutated in the synovial fluid of a patient with RA. The ACPAs recognized >3,000 unique peptides modified by either citrullination or carbamylation. This highly multireactive autoantibody feature was replicated for Ig sequences derived from B cells from the peripheral blood of other RA patients. The plasma cell-derived mAb were found to target distinct amino acid motifs and partially overlapping protein targets. They also conveyed different effector functions as revealed in an osteoclast activation assay.Conclusion: These findings suggest that the high level of cross-reactivity among RA autoreactive B cells is the result of different antigen encounters, possibly at different sites and at different time points. This is consistent with the notion that RA is initiated in one context, such as in the mucosal organs, and thereafter targets other sites, such as the joints.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Forsström, BjörnKTH,Systembiologi(Swepub:kth)u11i5nju (författare)
  • Sahlström, PeterKarolinska Institutet (författare)
  • Odowd, VictoriaUCB Pharma, Slough, Berks, England. (författare)
  • Israelsson, LenaKarolinska Institutet (författare)
  • Krishnamurthy, AkilanKarolinska Institutet (författare)
  • Badreh, SaraKarolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden. (författare)
  • Mathsson Alm, LindaUppsala universitet,Klinisk immunologi,Thermo Fisher Sci, Uppsala, Sweden.;Uppsala Univ, Uppsala, Sweden.(Swepub:uu)limat990 (författare)
  • Compson, JoanneUCB Pharma, Slough, Berks, England. (författare)
  • Ramsköld, DanielKarolinska Institutet (författare)
  • Ndlovu, WelcomeUCB Pharma, Slough, Berks, England. (författare)
  • Rapecki, StephenUCB Pharma, Slough, Berks, England. (författare)
  • Hansson, MonikaKarolinska Institutet (författare)
  • Titcombe, Philip J.Karolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden.;Univ Minnesota, Med Sch, Minneapolis, MN 55455 USA. (författare)
  • Bang, HolgerOrgentec Diagnost, Mainz, Germany. (författare)
  • Mueller, Daniel L.Univ Minnesota, Med Sch, Minneapolis, MN 55455 USA.,UCB Pharma, Slough, Berks, England. (författare)
  • Catrina, Anca I.Karolinska Institutet (författare)
  • Grönwall, CarolineKarolinska Institutet(Swepub:kth)u18yqokz (författare)
  • Skriner, KarlCharite, Berlin, Germany. (författare)
  • Nilsson, PeterKTH,Affinitets-proteomik(Swepub:kth)u1ws88sk (författare)
  • Lightwood, DanielUCB Pharma, Slough, Berks, England (författare)
  • Klareskog, LarsKarolinska Institutet (författare)
  • Malmström, VivianneKarolinska Institutet(Swepub:kth)u19ev7g4 (författare)
  • Karolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden.Systembiologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Arthritis & Rheumatology: WILEY71:2, s. 196-2092326-51912326-5205

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