B cells: deplete, repopulate, vaccinate.

Immunosuppression is essential for treatment of autoimmune rheumatic disease (AIRD), but it can have negative effects on the generation of effective immune responses. B cell depleting therapy (BCDT) is of particular concern, as it is known to affect the serological response to vaccination. With the continuing threat of the COVID-19 pandemic, rheumatologists are striving to determine how to get the best outcomes from both BCDT and SARS-CoV-2 vaccination in patients with severe AIRDs. Results from three new studies provide further evidence of the importance of the interval between rituximab treatment and vaccination, and suggest that B cell reconstitution is a biomarker for the probability of seroconversion.

In a study of 24 patients with AIRD who were treated with the BCDT rituximab, 35 with AIRD and other immunosuppressant therapy and 26 healthy individuals, 28 days after second doses of SARS-CoV-2 mRNA vaccines, neutralizing antibodies were present in 29%, 80% and 92% of participants in the respective groups. No patient treated with rituximab in the 6 months prior to vaccination had a neutralizing antibody response, and time since last rituximab infusion was associated with humoral response. Rituximab treatment did not affect T cell responses.

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In a second study of 56 patients with AIRD who were all treated with rituximab and who all received two doses of SARS-CoV-2 mRNA vaccine, time from last rituximab infusion (<6 months, 6–12 months or >12 months) was associated with rates of serological response (antibodies to the viral spike protein were detected in 14%, 45% and 87%, respectively). In addition, among the 39 participants whose B cell status was assessed, the seropositivity rate was 91.3% in those with detectable B cells who were vaccinated ≥6 months after rituximab treatment. According to corresponding author Robert Spiera, these results “suggest that B cell measurement could provide complementary information to timing that could help inform strategies to increase the likelihood of achieving a serological response in rituximab-treated patients with AIRD.”

Results … suggest that B cell reconstitution is a biomarker for the probability of seroconversion

In the third study, among 19 patients with AIRD and rituximab treatment, 12 with AIRD and other therapy and 30 healthy individuals, researchers identified the minimum concentration of B cells in the peripheral circulation of individuals who underwent seroconversion in response to SARS-CoV-2 vaccination. Corresponding author Thomas Dörner suggests that this concentration, of 10 B cells/µl, “is a candidate biomarker for a high likelihood of humoral vaccination response, and may support optimization of vaccination protocols among this vulnerable patient group.”