Inhibitory Anti-Peroxidasin Antibodies in Pulmonary-Renal Syndromes.

Autor:	McCall AS; Department of Nephrology and Hypertension, scott.mccall@vanderbilt.edu billy.hudson@vanderbilt.edu.; Center for Matrix Biology., Bhave G; Department of Nephrology and Hypertension.; Center for Matrix Biology.; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee., Pedchenko V; Department of Nephrology and Hypertension.; Center for Matrix Biology., Hess J; University of North Carolina Kidney Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and., Free M; University of North Carolina Kidney Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and., Little DJ; Department of Nephrology, Walter Reed Army Medical Center, Bethesda, Maryland., Baker TP; Department of Nephrology, Walter Reed Army Medical Center, Bethesda, Maryland., Pendergraft WF 3rd; University of North Carolina Kidney Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and., Falk RJ; University of North Carolina Kidney Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and., Olson SW; Department of Nephrology, Walter Reed Army Medical Center, Bethesda, Maryland., Hudson BG; Department of Nephrology and Hypertension, scott.mccall@vanderbilt.edu billy.hudson@vanderbilt.edu.; Center for Matrix Biology.; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.; Department of Cancer Biology.; Vanderbilt Ingram Cancer Center.; Department of Pathology, Microbiology, and Immunology, and.; Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, Tennessee.
Jazyk:	angličtina
Zdroj:	Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2018 Nov; Vol. 29 (11), pp. 2619-2625. Date of Electronic Publication: 2018 Oct 02.
DOI:	10.1681/ASN.2018050519
Abstrakt:	Background: Goodpasture syndrome (GP) is a pulmonary-renal syndrome characterized by autoantibodies directed against the NC1 domains of collagen IV in the glomerular and alveolar basement membranes. Exposure of the cryptic epitope is thought to occur via disruption of sulfilimine crosslinks in the NC1 domain that are formed by peroxidasin-dependent production of hypobromous acid. Peroxidasin, a heme peroxidase, has significant structural overlap with myeloperoxidase (MPO), and MPO-ANCA is present both before and at GP diagnosis in some patients. We determined whether autoantibodies directed against peroxidasin are also detected in GP. Methods: We used ELISA and competitive binding assays to assess the presence and specificity of autoantibodies in serum from patients with GP and healthy controls. Peroxidasin activity was fluorometrically measured in the presence of partially purified IgG from patients or controls. Clinical disease severity was gauged by Birmingham Vasculitis Activity Score. Results: We detected anti-peroxidasin autoantibodies in the serum of patients with GP before and at clinical presentation. Enriched anti-peroxidasin antibodies inhibited peroxidasin-mediated hypobromous acid production in vitro . The anti-peroxidasin antibodies recognized peroxidasin but not soluble MPO. However, these antibodies did crossreact with MPO coated on the polystyrene plates used for ELISAs. Finally, peroxidasin-specific antibodies were also found in serum from patients with anti-MPO vasculitis and were associated with significantly more active clinical disease. Conclusions: Anti-peroxidasin antibodies, which would previously have been mischaracterized, are associated with pulmonary-renal syndromes, both before and during active disease, and may be involved in disease activity and pathogenesis in some patients. (Copyright © 2018 by the American Society of Nephrology.)
Databáze:	MEDLINE
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