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

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 gen...

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Main Authors:	Ewa Cairns, Sheri Saunders, David A. Bell, Garth Blackler, Patrick Lac, Lillian Barra
Format:	Article
Language:	English
Published:	Elsevier 2020-01-01
Series:	Journal of Translational Autoimmunity
Subjects:	Rheumatoid arthritis Anti-citrullinated protein/peptide antibodies Anti-homocitrullinated (carbamylated) protein/peptide antibodies Sex Mouse model Shared epitope
Online Access:	http://www.sciencedirect.com/science/article/pii/S2589909020300204

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spelling	doaj-88f5c1d152fa46019ec103d333f762822020-12-17T04:51:08ZengElsevierJournal of Translational Autoimmunity2589-90902020-01-013100053The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid ArthritisEwa Cairns0Sheri Saunders1David A. Bell2Garth Blackler3Patrick Lac4Lillian Barra5Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada; Department of Medicine/Rheumatology, The University of Western Ontario, London, ON, CanadaDepartment of Microbiology and Immunology, The University of Western Ontario, London, ON, CanadaDepartment of Microbiology and Immunology, The University of Western Ontario, London, ON, CanadaDepartment of Microbiology and Immunology, The University of Western Ontario, London, ON, CanadaDepartment 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, CanadaDepartment 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.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.http://www.sciencedirect.com/science/article/pii/S2589909020300204Rheumatoid arthritisAnti-citrullinated protein/peptide antibodiesAnti-homocitrullinated (carbamylated) protein/peptide antibodiesSexMouse modelShared epitope
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Ewa Cairns Sheri Saunders David A. Bell Garth Blackler Patrick Lac Lillian Barra
spellingShingle	Ewa Cairns Sheri Saunders David A. Bell Garth Blackler Patrick Lac Lillian Barra The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis Journal of Translational Autoimmunity Rheumatoid arthritis Anti-citrullinated protein/peptide antibodies Anti-homocitrullinated (carbamylated) protein/peptide antibodies Sex Mouse model Shared epitope
author_facet	Ewa Cairns Sheri Saunders David A. Bell Garth Blackler Patrick Lac Lillian Barra
author_sort	Ewa Cairns
title	The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis
title_short	The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis
title_full	The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis
title_fullStr	The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis
title_full_unstemmed	The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis
title_sort	effect of sex on immune responses to a homocitrullinated peptide in the dr4-transgenic mouse model of rheumatoid arthritis
publisher	Elsevier
series	Journal of Translational Autoimmunity
issn	2589-9090
publishDate	2020-01-01
description	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.
topic	Rheumatoid arthritis Anti-citrullinated protein/peptide antibodies Anti-homocitrullinated (carbamylated) protein/peptide antibodies Sex Mouse model Shared epitope
url	http://www.sciencedirect.com/science/article/pii/S2589909020300204
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The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis

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