Distinct trajectories of humoral immune responses after SARS-CoV-2 mRNA vaccination in autoimmune inflammatory rheumatic diseases: A group-based trajectory analysis

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BACKGROUND: Patients with autoimmune inflammatory rheumatic diseases (AIRDs) are at a high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data on the effects of multiple (>3) vaccine doses and their influencing factors are limited. Understanding antibody dynamics after repeated vaccinations is essential for optimising vaccination strategies. Therefore, this study characterised the antibody response trajectories against SARS-CoV-2 and explored key clinical and immunological determinants. METHODS: This single-centre retrospective cohort study included patients with AIRDs who received SARS-CoV-2 vaccinations between 1 February and 6 December 2021. Serum neutralising antibody titres from the first to fifth vaccinations were analysed using group-based trajectory modelling (GBTM). The clinical characteristics and serum cytokine levels were compared between the response groups. RESULTS: The study included 293 patients with AIRDs. Three response trajectories were identified via GBTM: low responders (n = 13, 4·4%), middle responders (n = 122, 41·6%), and high responders (n = 158, 54·0%). Abatacept use was the strongest predictor of a low response (odds ratio 11·55, [95% confidence interval 2·27-58·82], p = 0·0032) but was also associated with a middle response (3·82, [1·18-12·29], p = 0·025). A middle response was also linked to older age (2·31 [1·38-3·85], p = 0·0014), mycophenolate mofetil use (3·03 [1·02-8·97], p = 0·045), anti-neutrophil cytoplasmic autoantibody-associated vasculitis (3·26 [1·29-8·19], p = 0·012), and rheumatoid arthritis (1·62 [1·02-8·97], p = 0·048), while systemic lupus erythematosus was inversely associated (0·49 [0·26-0·95], p = 0·035). Low responders exhibited elevated inflammatory mediators, including interleukin-6 and B-cell activating factor. CONCLUSION: We identified distinct antibody response trajectories in patients with AIRDs, including a subgroup with persistently low humoral immune responses despite repeated vaccinations. This study highlights the need for personalised vaccination strategies that consider individual clinical and immunological factors to optimise protection in this vulnerable populations.

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