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Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis
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- Andersson, Maria L.E. (författare)
- Lund University,Lunds universitet,Karolinska Institute,Karolinska Institutet,Karolinska Inst, Sweden,Spenshult Res & Dev Ctr, Sweden; Lund Univ, Sweden,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Spenshults artrit grupp,Forskargrupper vid Lunds universitet,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Spenshults arthritis group,Lund University Research Groups
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- Leu Agelii, Monica, 1977 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden.,Sahlgrenska Academy
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- Sareila, Outi, 1976 (författare)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,Karolinska Inst, Dept Med Biochem & Biophys, Sect Med Inflammat Res, Stockholm, Sweden.;Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden.,Sahlgrenska Academy
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- Andersson, M. L. E. (författare)
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- (creator_code:org_t)
- 2023-01-31
- 2023
- Engelska.
- Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:7, s. 1110-1119
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Objective. This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints.Methods. We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n = 2,110), Swedish age- and sex-matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE).Results. Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98-100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19-26%) of early RA patients seronegative for anti-cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE.Conclusion. A multiplex immunoassay with peptides from disease-related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- classification criteria
- citrullinated peptide
- revised criteria
- antibodies
- validation
- cohort
- Rheumatology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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