Sökning: id:"swepub:oai:DiVA.org:kth-279400" >
Serum and balf-deri...
Serum and balf-derived anti-JO1 autoantibodies exhibit high reactivity to distinct HISRS domains and associate with lung and joint involvement in patients with IIM/ASS
-
- Notarnicola, A. (författare)
- Karolinska Inst, Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
-
- Preger, C. (författare)
- Karolinska Inst, Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Struct Genom Consortium, Stockholm, Sweden.
-
- Lundström, S. (författare)
- Karolinska Inst, Stockholm, Sweden.;Dept Med Biochem & Biophys, Div Physiol Chem 1, Stockholm, Sweden.
-
visa fler...
-
- Renard, N. (författare)
- Karolinska Inst, Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
-
- Wigren, E. (författare)
- Karolinska Inst, Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Struct Genom Consortium, Stockholm, Sweden.
-
- Van Gompel, E. (författare)
- Karolinska Inst, Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
-
- Galindo-Feria, A. S. (författare)
- Karolinska Inst, Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
-
- Persson, Helena (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Proteinteknologi
-
- Fathi, M. (författare)
- Karolinska Inst, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Resp Med & Allergy, Bioclinicum, J7 30, Stockholm, Sweden.
-
- Grunewald, J. (författare)
- Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Resp Med & Allergy, Bioclinicum, J7 30, Stockholm, Sweden.
-
- Jakobsson, P. J. (författare)
- Karolinska Inst, Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
-
- Gräslund, S. (författare)
- Karolinska Inst, Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Struct Genom Consortium, Stockholm, Sweden.
-
- Lundberg, I. E. (författare)
- Karolinska Inst, Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
-
- Cerqueira, C. (författare)
- Karolinska Inst, Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
-
visa färre...
-
Karolinska Inst, Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. Karolinska Inst, Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Struct Genom Consortium, Stockholm, Sweden. (creator_code:org_t)
- 2020-06-02
- 2020
- Engelska.
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 79, s. 1109-1110
- Relaterad länk:
-
https://ard.bmj.com/...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
http://kipublication...
-
visa färre...
Abstract
Ämnesord
Stäng
- Autoantibodies that target aminoacyl transfer(t) RNA synthetases (aaRS) represent the serological marker of the anti-synthetase syndrome (ASS), a major subgroup of the idiopathic inflammatory myopathies (IIM) (1). Among the anti-aaRS, anti-histidyl tRNA synthetase (HisRS) autoantibodies (anti-Jo1) are the most common. Up to 90% of IIM/ASS patients diagnosed with interstitial lung disease (ILD) harbor anti-Jo1 autoantibodies (2).Objectives:Reactivity and affinity of anti-Jo1 autoantibodies from serum and broncheoalveolar lavage fluid (BALF) were investigated against HisRS autoantigen. Associations with clinical data from patients IIM/ASS were addressed.Methods:Total IgGs were purified by affinity chromatography. Samples and clinical data were obtained from: i) 26 anti-Jo1+patients (19 at diagnosis, 16/19 at follow-up, 7 BALF/matching serum at baseline; ii) 29 anti-Jo1-(25 serum at diagnosis, 4 BALF/matching serum at baseline); iii) 24 age/gender matched healthy controls. Anti-Jo1 IgG and IgA response against HisRS was evaluated by ELISA and western blot. Affinity was measured by surface plasmon resonance. HisRS full-length (HisRS-FL), two HisRS domains (ABD and CD), and two HisRS splice variants (WHEP and WHEP + ABD splice variant (SV)) were tested. Correlations between autoantibody reactivity and clinical data, at baseline and over disease course, were evaluated.Results:Anti-Jo1 autoantibodies from serum and lung bound HisRS-FL, WHEP and SV with high reactivity and affinity already at diagnosis and recognized both conformational and linear HisRS epitopes (Fig. 1). Levels of autoantibodies (against HisRS-FL, -domains and -splice variants) varied among patients and overtime. Patients with ILD, arthritis and less skin involvement presented higher anti-Jo1 titers compared to those with lower anti-Jo1 titers and to the anti-Jo1 negative group (Fig. 2). Anti-WHEP reactivity in BALF strongly correlated with poor pulmonary function.Conclusion:High reactivity and affinity at time of diagnosis indicates that autoimmunity against HisRS is most likely initiated before IIM/ASS diagnosis. Reactivity to specific splice variants of HisRS may be employed as diagnostic and prognostic markers.References:[1]Marguerie C, Bunn CC, Beynon HL, Bernstein RM, Hughes JM, So AK, Walport MJ: Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes. Q J Med 1990, 77(282):1019-1038[2]Richards TJ, Eggebeen A, Gibson K, Yousem S, Fuhrman C, Gochuico BR, Fertig N, Oddis CV, Kaminski N, Rosas IO et al: Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum 2009, 60(7):2183-2192.Fig. 1.Anti-Jo1 reactivity in total IgG purified from the first available serum sampleFig. 2.Reactivity of total anti-Jo1+ IgG purified from the first available serum close to IIM/ASS diagnosis in relation to clinical dataDisclosure of Interests:Antonella Notarnicola: None declared, Charlotta Preger: None declared, Susanna Lundström: None declared, Nuria Renard: None declared, Edvard Wigren: None declared, Eveline Van Gompel: None declared, Angeles Shunashy Galindo-Feria: None declared, Helena Persson: None declared, Maryam Fathi: None declared, Johan Grunewald: None declared, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Grant/research support from: Gesynta Pharma, AstraZeneca,, Susanne Gräslund: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Catia Cerqueira: None declared
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Publikations- och innehållstyp
- vet (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Notarnicola, A.
-
Preger, C.
-
Lundström, S.
-
Renard, N.
-
Wigren, E.
-
Van Gompel, E.
-
visa fler...
-
Galindo-Feria, A ...
-
Persson, Helena
-
Fathi, M.
-
Grunewald, J.
-
Jakobsson, P. J.
-
Gräslund, S.
-
Lundberg, I. E.
-
Cerqueira, C.
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Reumatologi och ...
- Artiklar i publikationen
-
Annals of the Rh ...
- Av lärosätet
-
Kungliga Tekniska Högskolan
-
Karolinska Institutet