The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis

Ewa Cairns; Sheri Saunders; David A. Bell; Garth Blackler; Patrick Lac; Lillian Barra

Journal of Translational Autoimmunity (Jan 2020)

The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis

Ewa Cairns,
Sheri Saunders,
David A. Bell,
Garth Blackler,
Patrick Lac,
Lillian Barra

Affiliations

Ewa Cairns: Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada; Department of Medicine/Rheumatology, The University of Western Ontario, London, ON, Canada
Sheri Saunders: Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada
David A. Bell: Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada
Garth Blackler: Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada
Patrick Lac: Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada; Current Address: Michael Smith Genome Sciences Centre, BC Cancer Research Centre, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
Lillian Barra: Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada; Department of Medicine/Rheumatology, The University of Western Ontario, London, ON, Canada; Corresponding author. Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario, Dental Sciences Building Rm. 3014, London, ON, N6A 5C1, Canada.

Journal volume & issue: Vol. 3
p. 100053

Abstract

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Rheumatoid Arthritis (RA) is more common and severe in women compared to men. Both women and men with RA express autoantibodies to post-translationally modified antigens, including citrullinated and homocitrullinated proteins or peptides. These autoantibodies are strongly linked with the HLA-DR4 gene. The objective of this study was to determine sex differences in immune responses to homocitrullinated antigens. We used a humanized animal model of RA, DR4-transgenic mice and immunized them with a homocitrullinated peptide called HomoCitJED. Immune responses in these mice were measured for splenocyte proliferation by tritiated thymidine incorporation, serum autoantibody production by ELISA and cytokine levels by multiplex. We found that T cell and antibody responses to homocitrullinated antigens were similar in male and female mice. However, we found sex differences in serum cytokine profiles with female mice having higher ratio of IL-1α to IL-5, suggesting imbalances in immune regulation. This is the first study to report that immune responses to homocitrullinated antigens can be differentiated by sex.

Published in Journal of Translational Autoimmunity

ISSN: 2589-9090 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: https://www.journals.elsevier.com/journal-of-translational-autoimmunity

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