Identification of a TCR signature in peripheral blood derived CD4+ T cells, associated with chronic chikungunya disease (CCD), suggests a conducive, female-biased, background immune profile

Koen Bartholomeeusen^1*Fabio Affaticati^2,3,4Betty Willems⁵Emilie Dhondt⁵Esther Bartholomeus^2,6,7Alvino Maestri⁸Sowath LY⁹Veasna Duong⁸Benson Ogunjimi^10,2,6,7Pieter Meysman^2,3,4Kris Laukens^2,3,4Tineke Cantaert^11,8Kevin K. Ariën^12,5

• ¹Virology Unit - Dept. Biomedical Sciences, Institute of Tropical Medicine Antwerp, Antwerp, Belgium
• ²Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerpen, Belgium
• ³Adrem Data Lab, Department of Mathematics and Computer Science, University of Antwerp, Antwerpen, Belgium
• ⁴Biomedical Informatics Research Network Antwerp (biomina), University of Antwerp, Antwerpen, Belgium
• ⁵Virology Unit - Dept. Biomedical Sciences, Institute of Tropical Medicine Antwerp, Antwerpen, Belgium
• ⁶Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerpen, Belgium
• ⁷Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerpen, Belgium
• ⁸Virology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia
• ⁹Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia
• ¹⁰Department of Paediatrics, Antwerp University Hospital, Antwerpen, Belgium
• ¹¹Immunology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia
• ¹²University of Antwerp, Department of Biomedical Sciences, Antwerpen, Belgium

To gain further insight into the physiopathology of CCD and to further the understanding of CD4+ T cell involvement we aimed to examine association of a specific TCR repertoire with CCD. To this end, we determined the TCR repertoire in bulk purified CD4+ T cells derived from peripheral blood from participants that did, or did not, progress to CCD, 6 months after confirmed infection during the 2020 CHIKV outbreak in Cambodia 34. TCR clustering and regression analyses allowed identification of CD4+ TCR signatures specifically associated with non-chronic or chronic patients. A noted preferential presence of the TCR signature associated with chronic disease in female participants further suggests a gender-biased immune profile conducive to progression to CCD. Together these findings further support a role for CD4+ T cells in the etiology and pathophysiology of CCD and suggest candidate biomarkers that may predict susceptibility for developing chronic symptoms following CHIKV infection.