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On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis
Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.ORCID-id: 0000-0003-1524-0851
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2019 (Engelska)Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, nr 12, s. 1616-1620Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective: Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains). Recently, we showed that N-glycosylation sites, which are required for the incorporation of V-domain glycans, are introduced following somatic hypermutation. However, it is currently unclear when V-domain glycosylation occurs. Further, it is unknown which factors might trigger the generation of V-domain glycans and whether such glycans are relevant for the transition towards RA. Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.

Methods: ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).

Results: V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset. Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.

Conclusion: Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life. Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA.

Ort, förlag, år, upplaga, sidor
BMJ Publishing Group Ltd, 2019. Vol. 78, nr 12, s. 1616-1620
Nationell ämneskategori
Reumatologi och inflammation
Identifikatorer
URN: urn:nbn:se:umu:diva-167073DOI: 10.1136/annrheumdis-2019-215698ISI: 000500726200016PubMedID: 31471298Scopus ID: 2-s2.0-85071766205OAI: oai:DiVA.org:umu-167073DiVA, id: diva2:1385008
Tillgänglig från: 2020-01-13 Skapad: 2020-01-13 Senast uppdaterad: 2023-03-23Bibliografiskt granskad

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Lundquist, AndersKokkonen, HeidiRantapää-Dahlqvist, Solbritt

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Lundquist, AndersKokkonen, HeidiToes, ReneRantapää-Dahlqvist, Solbritt
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Annals of the Rheumatic Diseases
Reumatologi och inflammation

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