63 research outputs found
Relationship between the clinical response to adalimumab treatment and serum levels of adalimumab and anti-adalimumab antibodies in patients with psoriatic arthritis
Relationship between serum trough infliximab levels, pretreatment C reactive protein levels, and clinical response to infliximab treatment in patients with rheumatoid arthritis
Objective: To investigate the relationship between serum trough infliximab levels and clinical response to infliximab treatment in patients with rheumatoid arthritis (RA). Methods: Disease activity and serum trough infliximab levels before and 2, 6, and 14 weeks after initiation of infliximab treatment at a dose of 3 mg/kg in a cohort of 105 patients with RA were assessed. Serum trough infliximab levels in responders and non-responders were compared. Additionally, the clinical responses of patients with high, intermediate, and low serum trough infliximab levels at 14 weeks were compared. Results: After 14 weeks of treatment non-responders had lower serum trough levels of infliximab than responders ( median (interquartile range) 0.5 (0.2 - 2.2) v 3.6 (1.4 - 8.2) mg/l; p <0.01)). Patients with low serum trough infliximab levels at 14 weeks had significantly less improvement in the 28 joint count Disease Activity Score (DAS28) score than patients with intermediate or high serum trough infliximab levels at 14 weeks. Pretreatment C reactive protein (CRP) levels correlated negatively with serum trough infliximab levels at 14 weeks after the start of treatment ( Spearman rank correlation r(s) = -.43, p <0.001). Conclusion: Serum trough levels of infliximab correlate with the clinical response to treatment with infliximab and pretreatment CRP levels. This study indicates that patients with high pretreatment CRP levels might benefit from higher dosages of infliximab or shorter dosing interval
Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and anti-tumour necrosis factor naive patients: a cohort study
Clinical response, pharmacokinetics, development of human anti-chimaeric antibodies, and synovial tissue response to rituximab treatment in patients with rheumatoid arthritis
Immunogenicity negatively influences the outcome of adalimumab treatment in Crohn's disease
Background: Adalimumab is an effective treatment in patients with Crohn's disease; as it is a humanized anti-tumour necrosis factor monoclonal antibody, immunogenicity is thought not to be of any significance. Aim: To assess whether antibodies to adalimumab (ATAs) affect adalimumab treatment outcome in patients with Crohn's disease previously treated with infliximab. Methods: A retrospective study was p
Circulating microparticles remain associated with complement activation despite intensive anti-inflammatory therapy in early rheumatoid arthritis
Arthritis development in patients with arthralgia is strongly associated with anti-citrullinated protein antibody status: a prospective cohort study
Ocrelizumab Concentration Is a Good Predictor of SARS-CoV-2 Vaccination Response in Patients with Multiple Sclerosis
High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages
Patients diagnosed with coronavirus disease 2019 (COVID-19) become critically ill primarily around the time of activation of the adaptive immune response. Here, we provide evidence that antibodies play a role in the worsening of disease at the time of seroconversion. We show that early-phase severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific immunoglobulin G (IgG) in serum of critically ill COVID-19 patients induces excessive inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for patients with severe COVID-19. First, inflammation is driven by high titers of anti-spike IgG, a hallmark of severe disease. Second, we found that anti-spike IgG from patients with severe COVID-19 is intrinsically more proinflammatory because of different glycosylation, particularly low fucosylation, of the antibody Fc tail. Low fucosylation of anti-spike IgG was normalized in a few weeks after initial infection with SARS-CoV-2, indicating that the increased antibody-dependent inflammation mainly occurs at the time of seroconversion. We identified Fc gamma receptor (Fc gamma R) Ila and FeyRIII as the two primary IgG receptors that are responsible for the induction of key COVID-19-associated cytokines such as interleukin-6 and tumor necrosis factor. In addition, we show that anti-spike IgG-activated human macrophages can subsequently break pulmonary endothelial barrier integrity and induce microvascular thrombosis in vitro. Last, we demonstrate that the inflammatory response induced by anti-spike IgG can be specifically counteracted by fostamatinib, an FDA- and EMA-approved therapeutic small-molecule inhibitor of Syk kinase.Proteomic
Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity
Background: Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs. Methods: IMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies. Results: In total, 193 IMID patients on ISP and 113 controls were included. Serum samples from 185 participants were available, with a median time of 173 days between infection and sample collection. The rate of seropositive IMID patients on ISPs was 78% compared to 100% in controls (p Pathophysiology and treatment of rheumatic disease
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