A recent study highlighted reduced adaptive immune responses to SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus (SLE), attributed to disease-associated B-cell endotypes and immune abnormalities. Patients with SLE exhibited diminished neutralization potency and breadth of anti–receptor-binding domain antibodies, with an identified association with extrafollicular immune pathways. Additionally, the researchers found that belimumab, commonly used in SLE management, further impaired vaccine responses by inhibiting naive B-cell priming and reducing critical circulating T-follicular helper cells.