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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Primary Immunodeficiencies
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1442749
This article is part of the Research Topic Inborn Errors of Immunity (IEI) Breaking Immune Homeostasis and Tolerance: A Key Role for T Regulatory Cells View all 6 articles

Immunological characterization of IgG subclass deficiency reveals decreased Tregs and increased circulating costimulatory and regulatory immune checkpoints

Provisionally accepted
Per Wågström Per Wågström 1,2*Maria Hjorth Maria Hjorth 2Daniel S. Appelgren Daniel S. Appelgren 2Janne Björkander Janne Björkander 3Charlotte Dahle Charlotte Dahle 2Mats Nilsson Mats Nilsson 4Åsa Nilsdotter-Augustinsson Åsa Nilsdotter-Augustinsson 2Jan Ernerudh Jan Ernerudh 2Sofia Nyström Sofia Nyström 2
  • 1 Ryhov Hospital Jönköping, Jönköping, Sweden
  • 2 Linköping University, Linköping, Östergötland, Sweden
  • 3 Wetterhälsan Health Care Center, Jönköping, Jönköping, Sweden
  • 4 Futurum, Region Jönköping County, Jönköping, Jönköping, Sweden

The final, formatted version of the article will be published soon.

    Background: Immunoglobulin G subclass deficiencies (IgGsd) comprise a wide clinical spectrum from no symptoms to repeated respiratory infections and risk for the development of lung damage. Our aims were to investigate whether the immunological phenotype of IgGsd patients on and off immunoglobulin replacement therapy (IgRT) was reflected in the clinical features of IgGsd. Method: Thirty patients with IgGsd were included in this prospective study of 18 months of IgRT, followed by 7-18 months of IgRT discontinuation. Blood samples were collected when patients were on and off IgRT and compared with samples from 34 cross-sectional healthy controls. An in-depth lymphocyte phenotyping was performed by flow cytometry and plasma levels of immune checkpoints were assessed. Results: IgG3 subclass deficiency was most common. Patients with IgGsd had decreased levels of activated T cells and B cells and plasma levels of negative immune checkpoint molecules correlated negatively with T cell and B cell activation. The decreased T cell activation level was unaffected by IgRT, while the B cell activation was partly restored. Of note, decreased levels of activated regulatory T cells (Tregs) were found in IgGsd patients and was partly restored during IgRT. The profile of comorbidities did not associate with Treg levels. Conclusion: IgGsd is associated with decreased B cell and T cell activation including Tregs, and increased plasma levels of negative immune checkpoint molecules. The consequence of reduced activated Tregs in IgGsd remains unclear. Decreased immune cell activation was partly restored during IgRT, demonstrating that IgRT may contribute to improved immune function in patients with IgGsd.

    Keywords: predominantly antibody deficiency, IgG subclass deficiency, Ig replacement therapy, T cells, B cells, Tregs, immune checkpoints

    Received: 02 Jun 2024; Accepted: 24 Jul 2024.

    Copyright: © 2024 Wågström, Hjorth, Appelgren, Björkander, Dahle, Nilsson, Nilsdotter-Augustinsson, Ernerudh and Nyström. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Per Wågström, Ryhov Hospital Jönköping, Jönköping, Sweden

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