RESUMO
This single-centre substudy of a double-blind, randomized, placebo-controlled trial aimed to determine the effect of 96âweeks of rosuvastatin on pulse wave velocity (PWV) in men (nâ=â55, 54âyears) with HIV at moderate cardiovascular risk (Framingham risk score 10-15%). PWV increased in both rosuvastatin [0.54âm/s standard error of difference (SED) 0.26] and placebo [0.50âm/s (SED 0.26), Pâ=â0.896] arms, leading to no difference in PWV at week 96 [rosuvastatin 9.40âm/s (SE 0.31); placebo 9.21âm/s (SE0.31), Pâ=â0.676].
Assuntos
Doenças Cardiovasculares , Infecções por HIV , Análise de Onda de Pulso , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/uso terapêutico , Rosuvastatina Cálcica/administração & dosagem , Masculino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Pessoa de Meia-Idade , Método Duplo-Cego , Placebos/administração & dosagem , Adulto , Sulfonamidas/uso terapêutico , Sulfonamidas/farmacologia , Resultado do Tratamento , Pirimidinas , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fluorbenzenos/uso terapêuticoRESUMO
Objectives: Amino acid variations across more than 30 immunoglobulin (Ig) allotypes may introduce structural changes that influence recognition by anti-Ig detection reagents, consequently confounding interpretation of antibody responses, particularly in genetically diverse cohorts. Here, we assessed a panel of commercial monoclonal anti-IgG1 clones for capacity to universally recognise two dominant IgG1 haplotypes (G1m-1,3 and G1m1,17). Methods: Four commercial monoclonal anti-human IgG1 clones were assessed via ELISAs and multiplex bead-based assays for their ability to bind G1m-1,3 and G1m1,17 IgG1 variants. Detection antibodies were validated against monoclonal IgG1 allotype standards and tested for capacity to recognise antigen-specific plasma IgG1 from G1m-1,3 and G1m1,17 homozygous and heterozygous SARS-CoV-2 BNT162b2 vaccinated (n = 28) and COVID-19 convalescent (n = 44) individuals. An Fc-specific pan-IgG detection antibody corroborated differences between hinge- and Fc-specific anti-IgG1 responses. Results: Hinge-specific anti-IgG1 clone 4E3 preferentially bound G1m1,17 compared to G1m-1,3 IgG1. Consequently, SARS-CoV-2 Spike-specific IgG1 levels detected in G1m1,17/G1m1,17 BNT162b2 vaccinees appeared 9- to 17-fold higher than in G1m-1,3/G1m-1,3 vaccinees. Fc-specific IgG1 and pan-IgG detection antibodies equivalently bound G1m-1,3 and G1m1,17 IgG1 variants, and detected comparable Spike-specific IgG1 levels between haplotypes. IgG1 responses against other human coronaviruses and influenza were similarly poorly detected by 4E3 anti-IgG1 in G1m-1,3/G1m-1,3 subjects. Conclusion: Anti-IgG1 clone 4E3 confounds assessment of antibody responses in clinical cohorts owing to bias towards detection of G1m1,17 IgG1 variants. Validation of anti-Ig clones should include evaluation of binding to relevant antibody variants, particularly as the role of immunogenetics upon humoral immunity is increasingly explored in diverse populations.