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Sökning: WFRF:(Lundberg J O) > (2020-2024) > Autoantibodies agai...

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FältnamnIndikatorerMetadata
00007930naa a2200613 4500
001oai:DiVA.org:kth-343651
003SwePub
008240222s2023 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:154883040
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-3436512 URI
0247 a https://doi.org/10.1136/annrheumdis-2023-eular.57382 DOI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1548830402 URI
040 a (SwePub)kthd (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Notarnicola, A.u Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.4 aut
2451 0a Autoantibodies against a subunit of mitochondrial respiratory chain complex I in inclusion body myositis
264 1b BMJ,c 2023
338 a print2 rdacarrier
500 a QC 20240222
520 a Background Autoantibodies are found in up to 80% of patients with idiopathic inflammatory myopathies (IIM) and are associated with distinct clinical phenotypes [1]. Autoantibodies targeting cytosolic 5´-nucleotidase 1A (anti-cN1A) are currently the only known serum biomarker for the subgroup inclusion body myositis (IBM) (2), although detected even in other autoimmune diseases.Objectives To identify new autoimmune targets in IIM by antigen bead array assay.Methods In a first cross-sectional exploratory study, 357 antigens representing 268 proteins were incubated with plasma samples from 219 IIM (108 Polymyositis (PM), 80 Dermatomyositis (DM) and 31 IBM) patients, 349 Systemic Lupus Erythematosus (SLE) patients and 306 population controls for screening of IgG reactivity by antigen bead array. All samples were identified in the local biobank of the Rheumatology clinic, Karolinska University Hospital. Interesting results obtained for the IBM subgroup were then validated in an independent larger cohort of 287 patients with IBM followed at nine European rheumatological or neurological centers. IBM serum samples were explored by antigen bead array and results validated by western blot. As controls, serum samples from 30 patients with PM and 30 with DM, HLA-matched with the IBM Swedish cohort, were included. Demographics, laboratory, clinical, and muscle biopsy data of the IBM cohort was retrieved.Results In the exploratory study IgG reactivity towards NADH dehydrogenase 1 α subcomplex 11 (NDUFA11), a subunit of the membrane-bound mitochondrial respiratory chain complex I, was discovered with higher frequency in the IBM (9,7%) than PM (2,8%) and DM samples (2,5%), although the difference was not statistically significant. Anti-NDUFA11 IgG was also found in 2,3% of SLE and 2,6% of population control samples. In the validation study anti-NDUFA11 autoantibodies were detected in 11/287 IBM patients (3,8%), 0/30 PM and 0/30 DM patients. Reactivity against NDUFA11 could be confirmed by western blot (Table 1, Figure 1). The eleven anti-NDUFA11 positive patients showed a trend of lower frequency of wheelchair/walker ever use and higher creatine kinase levels at time of IBM diagnosis compared to the anti-NDUFA11 negative group. Ragged red fibers were significantly more prevalent in anti-NDUFA11 positive than negative patients (p=0.04). Anti-cN1A autoantibodies were detected in 98/287 (34,1%) of IBM, 3/30 (10%) DM and 9/29 (31%) PM patients, p=0.03. Coexistence of anti NDUFA11 and anti-cN1A antibodies was observed in 3 IBM patients.Conclusion Our results reveal a new autoimmune target in the mitochondrial respiratory chain complex I that might be specifically associated with IBM. This is of particular interest as mitochondrial abnormalities are known histological findings in muscle biopsies of IBM patients.References [1]Galindo-Feria AS, Wang G, Lundberg IE. Autoantibodies: Pathogenic or epiphenomenon. Best Pract Res Clin Rheumatol. 2022;36(2):101767.[2]Herbert MK,et al. Disease specificity of autoantibodies to cytosolic 5’-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases. Ann Rheum Dis. 2016;75(4):696-701.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Reumatologi och inflammation0 (SwePub)302102 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Rheumatology and Autoimmunity0 (SwePub)302102 hsv//eng
653 a Autoantibodies
653 a Myositis
7001 a Hellström, Cekeu KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik4 aut0 (Swepub:kth)u1doy1fn
7001 a Horuluoglu, B.u Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Preger, C.4 aut
7001 a Bonomi, F.u Univ Florence, Univ Hosp Careggi, Div Rheumatol, Dept Expt & Clin Med, Florence, Italy.4 aut
7001 a De Paepe, B.4 aut
7001 a De Bleecker, J.u Ghent Univ Hosp, Dept Neurol & Neuromuscular Reference Ctr, Ghent, Belgium.;Ghent Univ Hosp, Neuromuscular Reference Ctr, Ghent, Belgium.4 aut
7001 a Van der Kooi, A. J.u Univ Amsterdam, Amsterdam Univ Med Ctr, Amsterdam Neurosci, Dept Neurol, Amsterdam, Netherlands.4 aut
7001 a De Visser, M.u Nice Univ Hosp, Res Canc & Aging, Inst Res Canc & Aging Nice, Nice, France.4 aut
7001 a Sacconi, S.u UCL, Ctr Rheumatol, London, England.;UCL, Dept Neuromuscular Dis, London, England.4 aut
7001 a Machado, P.u Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands.4 aut
7001 a Badrising, U. A.u Radboud Univ Nijmegen Med Ctr, Dept Neurol, Ctr Neurosci, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.4 aut
7001 a Rietveld, A.4 aut
7001 a Pruijn, G.u Radboud Univ Nijmegen, Inst Mol & Mat, Dept Biomol Chem 11, Nijmegen, Netherlands.4 aut
7001 a Rothwell, S.u Univ Manchester, Div Musculoskeletal & Dermatol Sci, Manchester, Lancs, England.4 aut
7001 a Lilleker, J. B.u Univ Manchester, Sch Biol Sci, Div Musculoskeletal & Dermatol Sci, Ctr Musculoskeletal Res, Manchester, Lancs, England.;Royal Hosp, Northern Care Alliance NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Dept Rheumatol, Manchester, Lancs, England.4 aut
7001 a Chinoy, H.u Univ Manchester, Sch Biol Sci, Div Musculoskeletal & Dermatol Sci, Ctr Musculoskeletal Res, Manchester, Lancs, England.;Royal Hosp, Northern Care Alliance NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Dept Rheumatol, Manchester, Lancs, England.;Univ Manchester, Ctr Musculoskeletal Res, Fac Biol Med & Hlth, Manchester, Lancs, England.;Hop La Pitie Salpetriere, Dept Internal Med & Clin Immunol, Paris, France.4 aut
7001 a Benveniste, O.4 aut
7001 a Svenungsson, E.u Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.4 aut
7001 a Idborg, H.u Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Jakobsson, P. J.u Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Nilsson, Peteru KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik4 aut0 (Swepub:kth)u1ws88sk
7001 a Lundberg, I. E.u Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Hop La Pitie Salpetriere, Dept Internal Med & Clin Immunol, Paris, France.4 aut
7102 a Karolinska Univ Hosp, Div Rheumatol, Dept Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.b Science for Life Laboratory, SciLifeLab4 org
7730 t Annals of the Rheumatic Diseasesd : BMJg 82, s. 574-574q 82<574-574x 0003-4967x 1468-2060
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-343651
8564 8u https://doi.org/10.1136/annrheumdis-2023-eular.5738
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:154883040

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