Impaired Generation of High-Affinity Memory B Cells and Neutralizing Antibodies Against SARS-CoV-2 in Adolescents and Young Adults With Juvenile Idiopathic Arthritis Treated With Tumor Necrosis Factor Inhibitors.

OBJECTIVE: We evaluated the immunogenicity of SARS-CoV-2 mRNA vaccines in patients with juvenile idiopathic arthritis (JIA), focusing on the generation of spike-specific memory B cells (MBCs) and of neutralizing antibodies, and assessed the impact of disease-modifying antirheumatic drugs, particularly tumor necrosis factor inhibitors (TNFi). METHODS: This study enrolled 35 adolescent and young adult patients with JIA. Data concerning disease characteristics and SARS-CoV-2 vaccination and infection were collected. We analyzed the frequency of low-affinity spike-specific and high-affinity spike-specific MBCs by flow cytometry. We measured total anti-spike antibodies levels using a chemiluminescence microparticle immunoassay and assessed neutralizing antibody titers with a microneutralization assay. RESULTS: Patients with JIA showed a reduced frequency of high-affinity MBCs compared to controls, with a notably poorer response among those receiving TNFi treatment. Additionally, their ability to bind the Omicron variant was significantly lower, particularly among TNFi-treated patients. SARS-CoV-2 infection alone was not able to generate high-affinity MBCs and neutralizing antibodies in patients with JIA. After receiving three vaccine doses, 43% of patients with JIA exhibited a reduced frequency of high-affinity MBCs and neutralizing antibodies. CONCLUSION: Patients with JIA undergoing treatment with TNFi demonstrated a diminished immunogenic response to SARS-CoV-2 vaccination, with lower frequencies of high-affinity MBCs and decreased neutralizing antibody titers. These findings underscore the need for customized vaccination protocols, including the potential use of booster doses, to enhance immunoprotection in this group. Additionally, the development of reliable biomarkers to distinguish between patients with and without adequate protective immunity is imperative to refine therapeutic interventions and ensure optimal patient outcomes.