HLA-DP diversity is associated with improved response to SARS-Cov-2 vaccine in hematopoietic stem cell transplant recipients
Juliette Villemonteix,
Vincent Allain,
Emma Verstraete,
Debora Jorge-Cordeiro,
Gérard Socié,
Alienor Xhaard,
Cyrille Feray,
Sophie Caillat-Zucman
Affiliations
Juliette Villemonteix
Laboratoire d’Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, 75010 Paris, France
Vincent Allain
Laboratoire d’Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, 75010 Paris, France; INSERM UMR 976, Université Paris Cité, Institut de Recherche Saint-Louis (IRSL), 75010 Paris, France
Emma Verstraete
Service d’hématologie-greffe, Hôpital Saint-Louis, AP-HP, Université Paris Cité, 75010 Paris, France
Debora Jorge-Cordeiro
Laboratoire d’Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, 75010 Paris, France
Gérard Socié
INSERM UMR 976, Université Paris Cité, Institut de Recherche Saint-Louis (IRSL), 75010 Paris, France; Service d’hématologie-greffe, Hôpital Saint-Louis, AP-HP, Université Paris Cité, 75010 Paris, France
Alienor Xhaard
Service d’hématologie-greffe, Hôpital Saint-Louis, AP-HP, Université Paris Cité, 75010 Paris, France
Cyrille Feray
Centre Hépato-Biliaire, Hôpital Paul-Brousse, AP-HP, Université Paris-Saclay, FHU Hepatinov, 94800 Villejuif, France; Institut National de la santé et de la recherche médicale (INSERM) UMR-S 1193, 94800 Villejuif, France
Sophie Caillat-Zucman
Laboratoire d’Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, 75010 Paris, France; INSERM UMR 976, Université Paris Cité, Institut de Recherche Saint-Louis (IRSL), 75010 Paris, France; Corresponding author
Summary: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients show lower humoral vaccine responsiveness than immunocompetent individuals. HLA diversity, measured by the HLA evolutionary divergence (HED) metrics, reflects the diversity of the antigenic repertoire presented to T cells, and has been shown to predict response to cancer immunotherapy. We retrospectively investigated the association of HED with humoral response to SARS-CoV-2 vaccine in allo-HSCT recipients. HED was calculated as pairwise genetic distance between alleles at HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci in recipients and their donors. Low anti-spike IgG levels (<30 BAU/mL) were associated with short time from allo-SCT and low donor DPB1-HED, mostly related to donor DPB1 homozygosity. The diversity of donor HLA-DP molecules, assessed by heterozygosity or sequence divergence, may thus impact the efficacy of donor-derived CD4 T cells to sustain vaccine-mediated antibody response in allo-HSCT recipients.
