Cristiana Sieiro Santos, MD: Immune Responses to mRNA Vaccines Against SARS-CoV-2 in Patients with Immune-mediated Inflammatory Rheumatic Diseases

Poster Presenter: Cristiana Sieiro Santos, MD, Rheumatology Resident, Complejo Asistencial Universitario de León, Spain

Poster Title: Immune Responses to mRNA Vaccines Against SARS-CoV-2 in Patients with Immune-mediated Inflammatory Rheumatic Diseases

Ignite Session 5A
Sunday, November 13 | 1:25–1:30 p.m. ET | Northern Liberties Stage
All ACR Convergence 2022 poster presentations are available on demand to registered meeting participants through October 31, 2023.

What is your poster about?
Messenger RNA (mRNA) SARS-CoV-2 vaccines have demonstrated extraordinary efficacy across all ages, but immunosuppressed patients were excluded from phase 3 trials. The objective of the study was to characterize B cell and T cell immune responses (CD4 and CD8) elicited by mRNA SARS-CoV-2 vaccines in patients with rheumatic diseases under immunotherapies and identify which drugs reduce the vaccine’s immunogenicity. We have included 100 naïve patients with SARS-CoV-2 with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-CoV-2 mRNA vaccine and compared responses with age-, gender-, and disease-matched patients with immune-mediated rheumatic disease (IMRD) not receiving immunosuppressors and with healthy controls. Patients with IMRD showed decreased seroconversion rates (80 percent versus 100 percent, p=0.03) and cellular immune responses (75 percent versus 100 percent, p=0.02). Patients on methotrexate achieved seroconversion in 62 percent of cases and cellular responses in 80 percent of cases. Abatacept decreased humoral and cellular responses. Rituximab (31 percent responders) and belimumab (50 percent responders) showed impaired humoral responses, but cellular responses were often preserved. Antibody titers were reduced with mycophenolate and azathioprine but preserved with leflunomide and anticytokines. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine’s immunogenicity.

Why did you decide to investigate this topic?
Patients with IMRDs are considered at risk for serious infections as a result of the underlying dysregulation of their immune system and the common use of targeted immune-modulating therapies and immunosuppression. The recent introduction of mRNA vaccines against SARS-CoV-2 is a major scientific breakthrough that will probably change current vaccine practices in the near future because they supply to a recipient’s own cells the information to produce exogenous proteins. Unmodified native antigen presentation by HLA I and II molecules to the immune system follows physiological routes; however, in IMRD patients, the exact correlate of the elicited immune responses that confers protection against infection is not yet fully known. We wanted to investigate this subject because there was little information available about the responses to mRNA SARS-CoV-2 vaccines in IMRDs.

What are you working on next related to this research?
We are now trying to determine the response to the Shingrix vaccination for shingles in patients with rheumatic diseases under treatment with Janus kinase (JAK) inhibitors.

What excites you most about your work?
This was one of the first studies about humoral and cellular response to mRNA SARS-CoV-2 vaccines in patients with IMRDs, including both CD4 and CD8 responses. According to our study, patients with IMRDs exhibit impaired SARS-CoV-2 vaccine immunogenicity, variably reduced with immunosuppressors. We have identified the drugs that reduce the vaccine’s immunogenicity and found that cumulative methotrexate and glucocorticoids can also affect the humoral response. We also found that humoral and cellular response are weakly correlated, which means that seroconversion by itself cannot reflect the vaccine’s immunogenicity. A lot of publications refer to a humoral response to mRNA SARS-CoV-2 vaccines in patients with IMRDs; however, little information is available regarding cellular responses, including both CD4 and CD8 responses.


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