Background: Elution of IgA from renal biopsies of patients with primary IgA nephropathy (IgAN) has suggested that mesangial IgA deposits are mainly multimeric in nature. This macromolecular IgA consists of dimeric and polymeric IgA and may be derived from the circulation. In children with IgAN, circulating macromolecular IgA levels correlate with bouts of macroscopic haematuria, but in adults a correlation with disease activity is less clear. Therefore, we have designed a novel method to assess the levels of polymeric IgA (pIgA) in sera from patients and controls.
Methods: A novel precipitation assay using recombinant CD89 was developed to measure pIgA. Polymeric IgA levels were measured in serum samples obtained from healthy volunteers (n = 21) and patients with IgAN (n = 51). Subsequently, serum pIgA levels were correlated with clinical parameters of disease.
Results: Serum pIgA levels were significantly increased in patients with IgAN. However, pIgA concentrations relative to total IgA were significantly lower in sera of patients with IgAN. No correlation was found between serum pIgA levels and clinical parameters of IgAN, such as decline of glomerular filtration rate, haematuria or proteinuria.
Conclusions: Although absolute levels of serum pIgA are increased in patients with IgAN as compared with controls, levels of pIgA relative to total serum IgA are lower. No significant correlation was found between serum concentrations of pIgA and clinical parameters of disease. These data support the notion that it is not the size alone, but the physicochemical composition of the macromolecular IgA that is the key factor leading to mesangial deposition.
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http://dx.doi.org/10.1093/ndt/gfh394 | DOI Listing |
Vaccines (Basel)
December 2024
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Background: A goal of mucosal human immunodeficiency virus type 1 (HIV-1) vaccines is to generate mucosal plasma cells producing polymeric IgA (pIgA)-neutralizing antibodies at sites of viral entry. However, vaccine immunogens capable of eliciting IgA neutralizing antibodies (nAbs) that recognize tier 2 viral isolates have not yet been identified.
Methods: To determine if stabilized native-like HIV-1 envelope (Env) trimers could generate IgA nAbs, we purified total IgA and IgG from the banked sera of six rhesus macaques that had been found in a previous study to develop serum nAbs after subcutaneous immunization with BG505.
Front Immunol
November 2024
Viral Zoonosis Research Unit, Department of Virology, Medicum, University of Helsinki, Helsinki, Finland.
Old World Orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS) characterized by increased vascular permeability and acute kidney injury (AKI). Despite the systemic nature of the disease, the virus enters humans through inhalation and therefore initially encounters the immunoglobulin class A (IgA) dominated mucosal immune system. Herein, we characterized systemic IgA responses and their potential relationship to the mucosal immune activation by examining blood samples obtained from patients hospitalized due to acute Puumala orthohantavirus infection.
View Article and Find Full Text PDFbioRxiv
November 2023
Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, Illinois 61801 USA.
Secretory (S) Immunoglobin (Ig) A is the predominant mucosal antibody, which mediates host interactions with commensal and pathogenic microbes, including . SIgA adopts a polymeric IgA structure that is bound by secretory component (SC). Despite significance, how SIgA supports diverse effector mechanisms is poorly characterized and SIgA-based therapies nonexistent.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
December 2023
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Background: The polymeric immunoglobulin receptor (pIgR) is a transmembrane transporter of polymeric IgA through the intestinal epithelium. Its overexpression has been reported in several cancers, but its role as a diagnostic and prognostic biomarker of oncogenesis is currently unclear.
Method: A literature search was conducted to summarize the functions of pIgR, its expression levels, and its clinical implications.
Curr Allergy Asthma Rep
October 2023
Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Purpose Of Review: Immunoglobulin A (IgA) mediates immune exclusion of antigens in the gut. Notably, IgA plays also a role in the prevention of IgE-mediated allergies and induction of immune tolerance. The present review addresses the role of IgA in the manifestation of IgE-mediated allergies, including allergen-specific immunotherapy (AIT), the regulation of IgA production, and the mechanism of IgA in immune cell activation.
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