CD73low B-cell phenotypes and distinct cytokine profiles in patients with active anti-Jo-1 antibody positive idiopathic inflammatory myopathies
Objectives We performed multiparameter phenotyping of peripheral B cells in anti-Jo-1 antibody positive idiopathic inflammatory myopathies (IIM) to delineate disease-associated immunological profiles and the influence of B cells on disease activity.Methods Purified B cells from peripheral blood mono...
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BMJ Publishing Group
2025-04-01
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| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/11/2/e005401.full |
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| author | Ingrid E Lundberg Vivianne Malmstrom Caroline Grönwall Begum Horuluoglu Charlotte De Vries Maho Nakazawa Karin Lodin |
| author_facet | Ingrid E Lundberg Vivianne Malmstrom Caroline Grönwall Begum Horuluoglu Charlotte De Vries Maho Nakazawa Karin Lodin |
| author_sort | Ingrid E Lundberg |
| collection | DOAJ |
| description | Objectives We performed multiparameter phenotyping of peripheral B cells in anti-Jo-1 antibody positive idiopathic inflammatory myopathies (IIM) to delineate disease-associated immunological profiles and the influence of B cells on disease activity.Methods Purified B cells from peripheral blood mononuclear cells from 16 patients with anti-Jo-1 antibody positive IIM (7 with untreated active IIM, 4 with active and treated IIM and 5 with inactive IIM) were analysed by multiparameter spectral flow cytometry. Dimensionality reduction and clustering analysis were applied to pre-gated CD19+B cells. Serum levels of 21 cytokines and anti-Jo-1 IgG autoantibodies were determined. All patients with IIM in this study were positive for anti-Jo-1 antibody.Results Anti-Jo-1 antibody levels correlated positively to disease activity. Flow cytometry demonstrated B-cell dysregulation with significantly lower CD73 expression on naïve, switched memory and double negative B cells in patients with active IIM. Clustering analysis further revealed expansions of CD73− IgM+naïve B cells and CD73− CD95+ switched memory B cells in active IIM. In unswitched memory B cells, CD73+CD21+ cells were decreased in active IIM. Patients with active IIM had significantly higher serum levels of B-cell activating factor, inducible protein-10, interleukin-6 and sCD40L which correlated with changes in B-cell populations.Conclusions Since CD73 has an immunoregulatory function by modulating the ATP/adenosine pathway, which is also targeted by methotrexate, the low CD73 B-cell expression in anti-Jo-1 antibody-positive IIM may lead to B-cell hyperactivation. These novel findings further highlight B cells as central in the pathogenesis of IIM and important therapeutic targets. |
| format | Article |
| id | doaj-art-9510f3c4a2ed4ae3aa2a99e2d77ecdf5 |
| institution | OA Journals |
| issn | 2056-5933 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMJ Publishing Group |
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| series | RMD Open |
| spelling | doaj-art-9510f3c4a2ed4ae3aa2a99e2d77ecdf52025-08-20T02:09:31ZengBMJ Publishing GroupRMD Open2056-59332025-04-0111210.1136/rmdopen-2024-005401CD73low B-cell phenotypes and distinct cytokine profiles in patients with active anti-Jo-1 antibody positive idiopathic inflammatory myopathiesIngrid E Lundberg0Vivianne Malmstrom1Caroline Grönwall2Begum Horuluoglu3Charlotte De Vries4Maho Nakazawa5Karin Lodin6Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, SwedenDivision of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, SwedenDivision of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, SwedenDivision of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, SwedenDivision of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, SwedenDivision of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, SwedenDepartment of Gastro, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, SwedenObjectives We performed multiparameter phenotyping of peripheral B cells in anti-Jo-1 antibody positive idiopathic inflammatory myopathies (IIM) to delineate disease-associated immunological profiles and the influence of B cells on disease activity.Methods Purified B cells from peripheral blood mononuclear cells from 16 patients with anti-Jo-1 antibody positive IIM (7 with untreated active IIM, 4 with active and treated IIM and 5 with inactive IIM) were analysed by multiparameter spectral flow cytometry. Dimensionality reduction and clustering analysis were applied to pre-gated CD19+B cells. Serum levels of 21 cytokines and anti-Jo-1 IgG autoantibodies were determined. All patients with IIM in this study were positive for anti-Jo-1 antibody.Results Anti-Jo-1 antibody levels correlated positively to disease activity. Flow cytometry demonstrated B-cell dysregulation with significantly lower CD73 expression on naïve, switched memory and double negative B cells in patients with active IIM. Clustering analysis further revealed expansions of CD73− IgM+naïve B cells and CD73− CD95+ switched memory B cells in active IIM. In unswitched memory B cells, CD73+CD21+ cells were decreased in active IIM. Patients with active IIM had significantly higher serum levels of B-cell activating factor, inducible protein-10, interleukin-6 and sCD40L which correlated with changes in B-cell populations.Conclusions Since CD73 has an immunoregulatory function by modulating the ATP/adenosine pathway, which is also targeted by methotrexate, the low CD73 B-cell expression in anti-Jo-1 antibody-positive IIM may lead to B-cell hyperactivation. These novel findings further highlight B cells as central in the pathogenesis of IIM and important therapeutic targets.https://rmdopen.bmj.com/content/11/2/e005401.full |
| spellingShingle | Ingrid E Lundberg Vivianne Malmstrom Caroline Grönwall Begum Horuluoglu Charlotte De Vries Maho Nakazawa Karin Lodin CD73low B-cell phenotypes and distinct cytokine profiles in patients with active anti-Jo-1 antibody positive idiopathic inflammatory myopathies RMD Open |
| title | CD73low B-cell phenotypes and distinct cytokine profiles in patients with active anti-Jo-1 antibody positive idiopathic inflammatory myopathies |
| title_full | CD73low B-cell phenotypes and distinct cytokine profiles in patients with active anti-Jo-1 antibody positive idiopathic inflammatory myopathies |
| title_fullStr | CD73low B-cell phenotypes and distinct cytokine profiles in patients with active anti-Jo-1 antibody positive idiopathic inflammatory myopathies |
| title_full_unstemmed | CD73low B-cell phenotypes and distinct cytokine profiles in patients with active anti-Jo-1 antibody positive idiopathic inflammatory myopathies |
| title_short | CD73low B-cell phenotypes and distinct cytokine profiles in patients with active anti-Jo-1 antibody positive idiopathic inflammatory myopathies |
| title_sort | cd73low b cell phenotypes and distinct cytokine profiles in patients with active anti jo 1 antibody positive idiopathic inflammatory myopathies |
| url | https://rmdopen.bmj.com/content/11/2/e005401.full |
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