Anti-proteinase 3 antibodies are implicated in the pathogenesis of small vessel vasculitis. These are primarily immunoglobulin G (IgG), with different subclasses predominating at different stages of disease. However, little is known of their respective roles in pathogenesis. We have previously shown that patient IgG4 was able to induce superoxide release from human neutrophils. To circumvent difficulties in separating the subclasses and additional differences in polyclonal patient antibodies we have generated monoclonal mouse/human IgG1 and IgG4 anti-proteinase 3 antibodies. Using these antibodies we have compared effects of IgG1 and IgG4 on human neutrophils in terms of superoxide release, cytokine production, degranulation and adhesion. Additionally we have investigated the interaction of the subclasses with Fc receptors expressed by the neutrophil. Chimeric antibodies were generated using human constant regions of each subclass and a variable region taken from a monoclonal antibody directed against proteinase 3. Superoxide release from neutrophils was measured by the reduction of ferricytochrome C, degranulation by the conversion of a synthetic colour substrate, cytokine release by interleukin-8 enzyme-linked immunosorbent assay, and adhesion by a flow-based adhesion assay. Fc receptor binding was assessed using blocking antibodies. The IgG4 anti-proteinase 3 was able to induce a dose-dependent release of superoxide, degranulation and adhesion. The antibody was not able to stimulate the secretion of interleukin-8. Fc receptors were essential for neutrophil stimulation and the constitutive Fc receptors were necessary for different stimulatory pathways. The IgG4 anti-proteinase 3 antibodies are able to stimulate neutrophils to undergo a pro-inflammatory response and may play a role in the pathogenesis of small vessel vasculitis.
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http://dx.doi.org/10.1111/j.1365-2567.2009.03108.x | DOI Listing |
Clin Chem Lab Med
January 2025
Laboratory of Clinical Pathology, Azienda Sanitaria Universitaria Integrata, Udine, Italy.
Objectives: External quality assessment (EQA) programs play a pivotal role in harmonizing laboratory practices, offering users a benchmark system to evaluate their own performance and identify areas requiring improvement. The objective of this study was to go through and analyze the UK NEQAS "Immunology, Immunochemistry and Allergy" EQA reports between 2012 and 2021 to assess the overall level of harmonization in autoimmune diagnostics and identify areas requiring improvement for future actions.
Methods: The EQA programs reviewed included anti-nuclear (ANA), anti-dsDNA, anti-centromere, anti-extractable nuclear antigen (ENA), anti-phospholipids, anti-neutrophil cytoplasm (ANCA), anti-proteinase 3 (PR3), anti-myeloperoxidase (MPO), anti-glomerular basement membrane (GBM), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), mitochondrial (AMA), liver-kidney-microsomal (LKM), smooth muscle (ASMA), APCA, and celiac disease antibodies.
Ocul Immunol Inflamm
December 2024
Division of Infectious Diseases, Integrated Health Services Institute (IHI), Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
Purpose: To report a complex case of serpiginous-like choroiditis (SLC) in a patient with anti-neutrophil cytoplasmic antibody (ANCA)-anti-proteinase 3 (PR3)-associated vasculitis with systemic involvement.
Methods: Case report.
Results: A 40-year-old male from a tuberculosis (TB)-endemic region presented with bilateral active SLC lesions.
Cureus
November 2024
Rheumatology, University Hospital of North Durham, Durham, GBR.
A male patient in his 30s with autism and depression presented to the emergency department with joint pain, a petechial/purpuric rash, sputum production, hemoptysis, and epistaxis. His mother reported a family history of autoimmune conditions. Examination revealed a non-blanching petechial/purpuric rash and tenderness in the feet and ankles.
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September 2024
General Medicine, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND.
PLoS One
October 2024
Department of Internal Medicine, CHU de Caen Normandie, Caen, France.
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