T Cell Repertoire Dynamics during Pregnancy in Multiple Sclerosis
Caren Ramien,
Erik C. Yusko,
Jan Broder Engler,
Stefanie Gamradt,
Kostas Patas,
Nils Schweingruber,
Anne Willing,
Sina Cathérine Rosenkranz,
Anke Diemert,
Anja Harrison,
Marissa Vignali,
Catherine Sanders,
Harlan S. Robins,
Eva Tolosa,
Christoph Heesen,
Petra C. Arck,
Alexander Scheffold,
Kenneth Chan,
Ryan O. Emerson,
Manuel A. Friese,
Stefan M. Gold
Affiliations
Caren Ramien
Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Erik C. Yusko
Adaptive Biotechnologies Corp., 1551 Eastlake Ave. E., Seattle, WA 98102, USA
Jan Broder Engler
Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Stefanie Gamradt
Charité - Universitätsmedizin Berlin, Klinik für Psychiatrie und Medizinische Klinik m.S. Psychosomatik, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
Kostas Patas
Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; Laboratory for Biopathology and Immunology, Eginition University Hospital, 72-74 Vasilissis Sophias Ave., 11528 Athens, Greece
Nils Schweingruber
Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; Klinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Anne Willing
Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Sina Cathérine Rosenkranz
Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; Klinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Anke Diemert
Klinik für Geburtshilfe und Pränatalmedizin, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Anja Harrison
Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; Department of Psychology, University of Central Lancashire, Preston, PR1 2HE Lancashire, UK
Marissa Vignali
Adaptive Biotechnologies Corp., 1551 Eastlake Ave. E., Seattle, WA 98102, USA
Catherine Sanders
Adaptive Biotechnologies Corp., 1551 Eastlake Ave. E., Seattle, WA 98102, USA
Harlan S. Robins
Adaptive Biotechnologies Corp., 1551 Eastlake Ave. E., Seattle, WA 98102, USA; Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109-1024, USA
Eva Tolosa
Institut für Immunologie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Christoph Heesen
Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; Klinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Summary: Identifying T cell clones associated with human autoimmunity has remained challenging. Intriguingly, many autoimmune diseases, including multiple sclerosis (MS), show strongly diminished activity during pregnancy, providing a unique research paradigm to explore dynamics of immune repertoire changes during active and inactive disease. Here, we characterize immunomodulation at the single-clone level by sequencing the T cell repertoire in healthy women and female MS patients over the course of pregnancy. Clonality is significantly reduced from the first to third trimester in MS patients, indicating that the T cell repertoire becomes less dominated by expanded clones. However, only a few T cell clones are substantially modulated during pregnancy in each patient. Moreover, relapse-associated T cell clones identified in an individual patient contract during pregnancy and expand during a postpartum relapse. Our data provide evidence that profiling the T cell repertoire during pregnancy could serve as a tool to discover and track “private” T cell clones associated with disease activity in autoimmunity. : Ramien et al. interrogate the immune repertoire in multiple sclerosis (MS) during pregnancy. They report a shift in T cell repertoire composition driven by a small number of “private” clones. This specific rather than global immunomodulation may help to explain the protective effect of pregnancy in human autoimmunity. Keywords: multiple sclerosis, pregnancy, T cell receptor α and β pairing, immunosequencing, repertoire sequencing, immune phenotyping, immune tolerance, human