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Longitudinal assess...
Longitudinal assessment of reactivity and affinity profile of anti-Jo1 autoantibodies to distinct HisRS domains and a splice variant in a cohort of patients with myositis and anti-synthetase syndrome
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- Notarnicola, Antonella (författare)
- Karolinska Institutet
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- Preger, Charlotta (författare)
- Karolinska Institutet
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- Lundstrom, Susanna L. (författare)
- Karolinska Institutet
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- Renard, Nuria (författare)
- Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Rheumatol, SE-17164 Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
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- Wigren, Edvard (författare)
- Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Rheumatol, SE-17164 Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Struct Genom Consortium, Toronto, ON, Canada.
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- Van Gompel, Eveline (författare)
- Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Rheumatol, SE-17164 Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;KULeuven, Lab Tissue Homeostasis & Dis, Skeletal Biol & Engn Res Ctr, Leuven, Belgium.
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- Galindo-Feria, Angeles S. (författare)
- Karolinska Institutet
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- Persson, Helena (författare)
- KTH,Läkemedelsutveckling,Science for Life Laboratory, SciLifeLab
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- Fathi, Maryam (författare)
- Karolinska Inst, Karolinska Univ Hosp, Dept Resp Med & Allergy, Bioclinicum, J7 30, SE-17176 Stockholm, Sweden.
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- Grunewald, Johan (författare)
- Karolinska Institutet
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- Jakobsson, Per-Johan (författare)
- Karolinska Institutet
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- Gräslund, Susanne (författare)
- Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Rheumatol, SE-17164 Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Struct Genom Consortium, Toronto, ON, Canada.
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- Lundberg, Ingrid E. (författare)
- Karolinska Institutet
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- Fernandes-Cerqueira, Catia (författare)
- Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Rheumatol, SE-17164 Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;4Dcell, 14 Rue La Beaune, F-93100 Montreuil, France.
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Karolinska Institutet Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Rheumatol, SE-17164 Stockholm, Sweden;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. (creator_code:org_t)
- 2022-03-02
- 2022
- Engelska.
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Ingår i: Arthritis Research & Therapy. - : Springer Nature. - 1478-6362. ; 24:1
- Relaterad länk:
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https://doi.org/10.1...
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https://arthritis-re...
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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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Abstract
Ämnesord
Stäng
- Background To address the reactivity and affinity against histidyl-transfer RNA synthetase (HisRS) autoantigen of anti-Jo1 autoantibodies from serum and bronchoalveolar lavage fluid (BALF) in patients with idiopathic inflammatory myopathies/anti-synthetase syndrome (IIM/ASSD). To investigate the associations between the reactivity profile and clinical data over time. Methods Samples and clinical data were obtained from (i) 25 anti-Jo1(+) patients (19 sera with 16 longitudinal samples and 6 BALF/matching sera at diagnosis), (ii) 29 anti-Jo1(-) patients (25 sera and 4 BALF/matching sera at diagnosis), and (iii) 27 age/gender-matched healthy controls (24 sera and 3 BALF/matching sera). Reactivity towards HisRS full-length (HisRS-FL), three HisRS domains (WHEP, antigen binding domain (ABD), and catalytic domain (CD)), and the HisRS splice variant (SV) was tested. Anti-Jo1 IgG reactivity was evaluated by ELISA and western blot using IgG purified from serum by affinity chromatography. In paired serum-BALF, anti-Jo1 IgG and IgA reactivity was analyzed by ELISA. Autoantibody affinity was measured by surface plasmon resonance using IgG purified from sera. Correlations between autoantibody reactivity and clinical data were evaluated at diagnosis and longitudinally. Results Anti-Jo1 IgG from serum and BALF bound HisRS-FL, WHEP, and SV with high reactivity at the time of diagnosis and recognized both conformation-dependent and conformation-independent HisRS epitopes. Anti-HisRS-FL IgG displayed high affinity early in the disease. At the time of IIM/ASSD diagnosis, the highest autoantibody levels against HisRS-FL were found in patients ever developing interstitial lung disease (ILD) and arthritis, but with less skin involvement. Moreover, the reactivity of anti-WHEP IgG in BALF correlated with poor pulmonary function. Levels of autoantibodies against HisRS-FL, HisRS domains, and HisRS splice variant generally decreased over time. With some exceptions, longitudinal anti-HisRS-FL antibody levels changed in line with ILD activity. Conclusion High levels and high-affinity anti-Jo1 autoantibodies towards HisRS-FL were found early in disease in sera and BALF. In combination with the correlation of anti-HisRS-FL antibody levels with ILD and ILD activity in longitudinal samples as well as of anti-WHEP IgG in BALF with poor pulmonary function, this supports the previously raised hypothesis that the lung might have a role in the immune reaction in anti-Jo1-positive patients.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- Anti-Jo1
- HisRS
- Longitudinal samples
- ILD
- Autoantibodies
- Affinity
- Reactivity
- BALF
- Idiopathic inflammatory myopathies
- Anti-synthetase syndrome
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Notarnicola, Ant ...
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Preger, Charlott ...
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Lundstrom, Susan ...
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Renard, Nuria
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Wigren, Edvard
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Van Gompel, Evel ...
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Galindo-Feria, A ...
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Persson, Helena
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Fathi, Maryam
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Grunewald, Johan
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Jakobsson, Per-J ...
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Gräslund, Susann ...
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Lundberg, Ingrid ...
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Fernandes-Cerque ...
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