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Patients with anti-...
Patients with anti-Jo1 antibodies display a characteristic IgG Fc-glycan profile which is further enhanced in anti-Jo1 autoantibodies
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- Fernandes-Cerqueira, C (författare)
- Karolinska Institutet
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Renard, N (författare)
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- Notarnicola, A (författare)
- Karolinska Institutet
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- Wigren, E (författare)
- Karolinska Institutet
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- Graslund, S (författare)
- Karolinska Institutet
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- Zubarev, RA (författare)
- Karolinska Institutet
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- Lundberg, IE (författare)
- Karolinska Institutet
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- Lundstrom, SL (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2018-12-18
- 2018
- Engelska.
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 17958-
- Relaterad länk:
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https://www.nature.c...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- IgG Fc-glycans affect IgG function and are altered in autoimmune diseases and autoantibodies. Anti-histidyl tRNA synthetase autoantibodies (anti-Jo1) are frequent in patients with idiopathic inflammatory myopathies (IIM) and anti-synthetase syndrome (ASS) with associated interstitial lung disease (ILD). Thus, we hypothesized that the total-IgG Fc-glycans from Jo1+ versus Jo1− patients and anti-Jo1-IgG would show characteristic differences, and that particular Fc-glycan features would be associated with specific clinical manifestations. By proteomics based mass spectrometry we observed a high abundance of agalactosylated IgG1 Fc-glycans in ASS/IIM patients (n = 44) compared to healthy age matched controls (n = 24). Using intra-individual normalization of the main agalactosylated glycan (FA2) of IgG1 vs FA2-IgG2, ASS/IIM and controls were distinguished with an area under the curve (AUC) of 79 ± 6%. For Jo1+ patients (n = 19) the AUCs went up to 88 ± 6%. Bisected and afucosylated Fc-glycans were significantly lower in Jo1+ compared to Jo1− patients. Anti-Jo1-IgG enriched from eleven patients contained even significantly lower abundances of bisected, afucosylated and galactosylated forms compared to matched total-IgG. ASS and ILD diagnosis, as well as lysozyme and thrombospondin correlated with Jo1+ characteristic Fc-glycan features. These results suggest that the anti-Jo1+ patient Fc-glycan profile contains phenotype specific features which may underlie the pathogenic role of Jo1 autoantibodies.
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