Timing is essential: Humoral and cellular responses to SARS-CoV-2 vaccination in a cohort of patients with auto-immune diseases treated with rituximab

时机至关重要:接受利妥昔单抗治疗的一组自身免疫性疾病患者对 SARS-CoV-2 疫苗接种的体液和细胞反应

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作者:Irène Gallais Sérézal, Laurie Spehner, Marie Kroemer, Inès Bourezane, Nadine Meaux-Ruault, Clément Prati, Andréa Pastissier, Juliette Lodovichetti, Pierre Tiberghien, François Aubin

Abstract

Rituximab (RTX), an anti CD20 monoclonal antibody, is now a gold standard treatment for several auto-immune and chronic inflammatory diseases. Receiving RTX exposes patients to more severe infections as vaccinations become virtually inefficient in terms of B cell responses. During the COVID-19 crisis, RTX-exposed patients exhibited more severe forms of the disease, and in some cases, the introduction of RTX was delayed or avoided to protect patients as much as possible against SARS-CoV-2 infections. We retrospectively collected cellular and humoral responses from thirteen patients with dermatological and rheumatological autoimmune diseases who had been vaccinated after receiving RTX. Memory T cells subsets from patients that exposed to RTX showed few differences when compared to a cohort of healthy donors. The IFNᵧ ELISpot assay using SARS-CoV-Prot_S1 showed that eight patients exhibited a positive response that was neither correlated to the time between RTX infusion and the sampling nor to the time between RTX and the vaccination. Conversely, analysis of the SARS-CoV-2 serology showed a clearly lower binding antibody units per mL in case of recent RTX infusion. The safe threshold forconsistently positive serology was to vaccinate at least 300 days after RTX infusion (p = 0.02). Our data illustrate the difficulty in obtaining a satisfactory response to vaccination after RTX treatment within almost a year after the latest infusion, and emphasize the need to better evaluate the risk of relapses in auto-immune diseases before administering RTX in order to maintain RTX only in patients whose medical situation requires it.

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