Anti-IL13 Monoclonal antibody, clone C-Q7 [FITC]

Background: Wiskott-Aldrich syndrome (WAS), X-linked thrombocytopenia (XLT), and X-linked neutropenia, which are caused by WAS mutations affecting Wiskott-Aldrich syndrome protein (WASp) expression or activity, manifest in immunodeficiency, autoimmunity, genomic instability, and lymphoid and other cancers. WASp supports filamentous actin formation in the cytoplasm and gene transcription in the nucleus. Although the genetic basis for XLT/WAS has been clarified, the relationships between mutant forms of WASp and the diverse features of these disorders remain ill-defined. Objective: We sought to define how dysfunctional gene transcription is causally linked to the degree of T-H cell deficiency and genomic instability in the XLT/WAS clinical spectrum. Methods: In human T(H)1- or T(H)2-skewing cell culture systems, cotranscriptional R-loops (RNA/DNA duplex and displaced single-stranded DNA) and DNA double-strand breaks (DSBs) were monitored in multiple samples from patients with XLT and WAS and in normal T cells depleted of WASp. Results: WASp deficiency provokes increased R-loops and R-loop-mediated DSBs in T(H)1 cells relative to T(H)2 cells. Mechanistically, chromatin occupancy of serine 2-unphosphorylated RNA polymerase II is increased, and that of topoisomerase 1, an R-loop preventing factor, is decreased at R-loop-enriched regions of IFNG and TBX21 (T(H)1 genes) in T(H)1 cells. These aberrations accompany increased unspliced (intron-retained) and decreased spliced mRNA of IFNG and TBX21 but not IL13 (T(H)2 gene). Significantly, increased cellular load of R-loops and DSBs, which are normalized on RNaseH1-mediated suppression of ectopic R-loops, inversely correlates with disease severity scores. Conclusion: Transcriptional R-loop imbalance is a novel molecular defect causative in TH1 immunodeficiency and genomic instability in patients with WAS. The study proposes that cellular R-loop load could be used as a potential biomarker for monitoring symptom severity and prognostic outcome in the XLT-WAS clinical spectrum and could be targeted therapeutically.

Asthma, a chronic lung disease characterized by obstruction of airway passage is characterized by inflammation and hyperresponsiveness with increase in the number of eosinophils. Interleukin-13, plays a significant role in causing inflammation during an asthmatic attack by bronchial constriction. Mometasone, a glucocorticoid has been used as the first line of administration for people affected with asthma for almost a decade. However, in several cases, people treated with mometasone have faced systemic and local side effects. To reduce these side effects, we hypothesized vitamin D that can be used as a substitute to mometasone. For this purpose, we employed the use of molecular docking and simulation studies for comparative study. The docking studies revealed the binding residues of interleukin-13 which are bound to the active site. Among all, we noticed three binding residue Leu83, His84 and Arg86 common for both mometasone and vitamin D. Also, the binding energies share a significant similarity between them. The docked complexes of mometasone and vitamin D with interleukin-13 were evaluated with molecular dynamics simulation. Consistently, the MD analysis uncovered the interesting note on conformational adaptation between the complexes as well as that vitamin D has the complementary binding efficiency to interleukin-13 as compared to mometasone. The substitution of vitamin D might provide a promising gateway to reduce the side effects caused by mometasone and also reduce the cost for treatment of asthma patients.