Publications by authors named "R H Higgs"
Objective: Neutrophils play an important role in regulating immune and inflammatory responses in patients with rheumatoid arthritis (RA). We assessed whether baricitinib, a JAK1/JAK2 inhibitor, could reduce neutrophil activation and whether a neutrophil activation score could predict treatment response.
Methods: Markers of neutrophil activation, calprotectin, and neutrophil extracellular traps (NETs) were analyzed using enzyme-linked immunosorbent assay in plasma from patients with RA (n = 271) and healthy controls (n = 39).
Motivation: On-target gene knockdown, using siRNA, ideally results from binding fully complementary regions in mRNA transcripts to induce direct cleavage. Off-target siRNA gene knockdown can occur through several modes, one being a seed-mediated mechanism mimicking miRNA gene regulation. Seed-mediated off-target effects occur when the ∼8 nucleotides at the 5' end of the guide strand, called a seed region, bind the 3' untranslated regions of mRNA, causing reduced translation.
View Article and Find Full Text PDFAs part of the non-clinical safety package characterizing bamlanivimab (SARS-CoV-2 neutralizing monoclonal antibody), the risk profile for antibody-dependent enhancement of infection (ADE) was evaluated in vitro and in an African green monkey (AGM) model of COVID-19. In vitro ADE assays in primary human macrophage, Raji, or THP-1 cells were used to evaluate enhancement of viral infection. Bamlanivimab binding to C1q, FcR, and cell-based effector activity was also assessed.
View Article and Find Full Text PDFBiologic drugs (therapeutic proteins or peptides) have become one of the most important therapeutic modalities over the past few decades. Drug-induced immunogenicity is a significant concern as it may affect safety, tolerability, and efficacy. With more sensitive and drug-tolerant screening assays in use today, reliable estimation of anti-drug-antibody (ADA) titer has become more important for understanding clinically relevant ADA levels.
View Article and Find Full Text PDFArticle Synopsis
- Mirikizumab, an anti-IL-23 monoclonal antibody, showed effectiveness in treating moderate-to-severe ulcerative colitis in clinical trials, particularly after 12 weeks of treatment.
- The study analyzed gene expression at week 52 in patients who responded to mirikizumab at week 12, using biopsies to identify differentially expressed genes (DEGs) and maintaining their expression.
- Results indicated that mirikizumab responders had significantly more transcriptional changes and consistency in gene expression at week 52 compared to placebo responders, suggesting a unique molecular healing pathway related to IL-23 inhibition.