Project description:Regulatory T cells (Tregs) are frequently functionally impaired in patients with Granulomatosis with PolyAngiitis (GPA). However, the mechanism underlying their impaired function is unknown. Here, we hypothesized that Treg dysfunction in GPA is due to altered microRNA (miRNA) expression.
Project description:Objectives: To determine whether disease processes related to granulomatosis with polyangiitis (GPA) are reflected in gene expression profiles of nasal mucosa. Methods: Nasal brushings of the inferior turbinate were obtained from 32 patients with GPA (10 with active nasal disease, 13 with prior nasal disease, 9 with no history of nasal disease) and a composite comparator group with and without inflammatory nasal disease (12 healthy people, 15 with sarcoidosis, 8 with allergic rhinitis). Differential gene expression was assessed between subgroups of GPA and comparators. Results: 339 genes were differentially expressed between the GPA and comparator groups (absolute fold change > 1.5; false discovery rate < 0.05). Top canonical pathways upregulated in nasal brushings from patients with GPA include granulocyte adhesion and diapedesis (p=8.6 E-22), agranulocyte adhesion and diapedesis (p=1.3 E-14), interleukin 10 signaling (3.0 E-11), and TREM1 signaling (9.0 E-11). A set of genes differentially expressed in GPA independent of nasal disease activity status included genes related to epithelial barrier integrity (fibronectin 1, desmosomal proteins) and several matricellular proteins (e.g. osteonectin, osteopontin). Significant overlap of differentially expressed genes was observed between active and prior nasal disease GPA subgroups. Peripheral blood neutrophil and mononuclear gene expression levels associated with GPA were similarly altered in the nasal gene expression profiles of patients with active or prior nasal disease. Conclusions: Profiling the nasal transcriptome in GPA reveals gene expression signatures related to innate immunity, inflammatory cell chemotaxis, extracellular matrix composition, and epithelial barrier integrity. Airway-based expression profiling is feasible and informative in GPA.
Project description:Diagnosis of inflamed human orbit tissue with standard clinical and histopathology evaluation data is imprecise. A large number of these patients are diagnosed with the catch-all classification of nonspecific orbital inflammation (NSOI). We utilized gene expression analysis of orbit biopsies to assist in the classification of sarcoidosis, granulomatosis with polyangiitis (GPA), thyroid eye disease (TED), IgG4-associated disease, and subdivisions of NSOI. As part of this process, we are investigating correlations between gene expression levels and disease characteristics.
Project description:Diagnosis of inflamed human lacrimal gland with standard clinical and histopathology evaluation data is imprecise. A large number of these patients are diagnosed with the catch-all classification of nonspecific orbital inflammation (NSOI). We utilized gene expression analysis of lacrimal gland biospy/surgical waste tissues to assist in the classification of sarcoidosis, granulomatosis with polyangiitis (GPA), thyroid eye disease (TED), and subdivisions of NSOI. As part of this process, we are investigating correlations between gene expression levels and disease characteristics.
Project description:<p>The purpose of this study is to learn about reproductive health, including fertility and pregnancies, in people with vasculitis.</p> <p>All patients enrolled in the Vasculitis Clinical Research Consortium's Contact Registry will be invited via email to participate in this study. The Contact Registry includes people who self-identify as having one of 11 vasculities: Behçet's disease, central nervous system vasculitis, drug-induced vasculitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss), giant cell arteritis, granulomatosis with polyangiitis (Wegener's), Henoch-Schoenlein purpura, Kawasaki disease, microscopic polyangiitis, polyarteritis nodosa, or Takayasu arteritis. People voluntarily enroll in this Registry with the understanding that they will receive information about clinical studies for which they might be eligible. The introductory email included basic information about the study and all of the required elements for informed consent in a brief format. Once participants agreed to participate in the study, they were directed to an online questionnaire.</p>
