Researchers have uncovered that patients with systemic lupus erythematosus may exhibit reduced adaptive immune responses to SARS-CoV-2 mRNA vaccination, highlighting the role of disease-associated B-cell endotypes and immune abnormalities, according to a recent study.

In the study, published in Nature Immunology, the researchers performed a comprehensive serological and cellular analysis, revealing that patients with systemic lupus erythematosus (SLE) produced anti–receptor-binding domain (RBD) antibodies with reduced avidity, resulting in diminished neutralization potency and breadth.

The researchers identified a persistent antispike response in immunoglobulin-D–negative, CD27-negative B-cell populations, which were more prevalent in the patients with SLE. These cells are associated with extrafollicular immune pathways, suggesting a disease-driven immune dysregulation that may underlie vaccine response deficits.

Furthermore, the researchers developed and validated an extrafollicular B- and T-cell score, which strongly correlated with vaccine efficacy. The patients with higher scores experienced reduced neutralizing antibody responses and compromised T-cell immunity.

Meanwhile, belimumab, an anti–B-cell activating factor monoclonal antibody often used to manage SLE, was found to further impair vaccine responses. The treatment inhibited naive B-cell priming and unexpectedly reduced circulating T-follicular helper cells that are critical for robust humoral responses.

"Patients with SLE exhibited reduced avidity of anti–receptor-binding domain antibodies, leading to decreased neutralization potency and breadth," said lead study author Caterina E. Faliti, of the Department of Medicine in the Division of Rheumatology at the Lowance Center for Human Immunology at Emory University, and her colleagues.

The findings suggested that unique disease-associated immune profiles in patients with SLE, particularly involving extrafollicular B- and T-cell dynamics, contribute to suboptimal vaccine efficacy. This could inform strategies for improving vaccination outcomes in immunocompromised populations, such as timing vaccines relative to immunosuppressive therapy or developing tailored vaccine formulations.

The study authors disclosed no conflicts of interest.