Background/Purpose: The immunological responses following 3 doses of SARS-CoV2 mRNA vaccination in rheumatic disease patients are unclear. Furthermore, the impact of SARS-CoV2 mRNA vaccination on the expression of rheumatic disease biomarkers remains unclear. To address these questions, we longitudinally evaluated the immunological responses and disease marker changes in a small cohort of rheumatic patients following 2 and 3 doses of SARS-CoV2 mRNA vaccination. These included immune cell homeostasis, antibody titers and surrogate neutralization ability and disease markers, such as anti-dsDNA concentration, expression of type I IFN signatures (ISG), and the frequency of “double-negative” (DN) fraction of B cells expressing CD11c and not CD21 (DN2 B cells).

Methods: We collected plasma, peripheral blood mononuclear cell (PBMC), and whole blood RNA samples before the first dose, 1 month after the second dose, 3-4 months after the second dose, and 1 month after the third dose of SARS-CoV2 mRNA vaccination (either Pfizer or Moderna vaccine) from 11 patients with systemic lupus erythematosus, 10 patients with psoriatic arthritis, 4 patients with Sjogren’s syndrome, 2 patient with ankylosing spondylitis, and 1 patient with inflammtory myositis. Convalescent plasma samples, plasma samples from 10 healthy donors (1 month, or 3-4 months after the second dose), and plasma samples from donors before COVID-19 pandemic were included as controls. The titers of anti-SARS-CoV2 spike protein IgG and IgA were measured by ELISA. A surrogate neutralization assay was utilized to measure the ability of plasma to block the interaction between the ACE2 receptor protein and the receptor binding domain (RBD) of the viral spike protein. Anti-dsDNA concentration was measured by ELISA. Expression of 3 type I interferon signature genes (IFI44, IFIT1, and MX1) were measured by real-time PCR. The frequency of DN2 B cells was measured by flow cytometry.

Results: Our data showed that most of the patients generated high level of SARS-CoV2 spike specific neutralizing antibodies that were comparable to those in healthy donors after 2 doses of mRNA vaccines. The antibody level declines overtime, but recovered after the third dose of vaccine. Two patients who received rituximab treatment with very low B cell frequency exhibited substantial reduction of antibody level and neutralization ability. The changes of ds-DNA concentration and expression of type I IFN signature genes were highly variable. While some patients showed elevated ds-DNA concentration and expression of ISG after 2 doses of vaccination, these parameters largely returned to pre-vaccination level after the third dose of vaccination. Frequency of DN2 B cells remained largely stable over the course of vaccination.

Conclusion: Rheumatic disease patients without rituximab treatment have largely normal antibody responses towards SARS-CoV2 mRNA vaccination. Disease associated biomarkers remain largely stable over 3 doses of vaccination, suggesting that SARS-CoV2 mRNA vaccination may not exacerbate rheumatic diseases.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immune-responses-and-disease-marker-changes-following-sars-cov-2-mrna-vaccination-in-a-cohort-of-rheumatic-disease-patients/