Petr Kosztyu1, Martin Hill2, Jana Jemelkova1, Lydie Czernekova1, Leona Raskova Kafkova1, Miroslav Hruby3, Karel Matousovic4, Karel Vondrak5, Josef Zadrazil3, Ivan Sterzl2, Jiri Mestecky6,7,8, Milan Raska1,6,9. 1. Department of Immunology, Faculty of Medicine and Dentistry, Palacky University, Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. 2. Department of Steroids and Proteohormones and Department of Clinical Immunology, Institute of Endocrinology, Prague, Czech Republic. 3. Department of Internal Medicine III Nephrology, Rheumatology and Endocrinology, Palacky University Olomouc, Olomouc, Czech Republic. 4. Department of Medicine, Second School of Medicine, Charles University, Prague and University Hospital Motol, Prague, Czech Republic. 5. Department of Pediatrics, Second School of Medicine, Charles University, Prague and University Hospital Motol, Prague, Czech Republic. 6. Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA. 7. Division of Immunology and Gnotobiology Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic. 8. Institute of Immunology and Microbiology, First School of Medicine, Charles University, Prague, Czech Republic. 9. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
Abstract
BACKGROUND/AIMS: IgA nephropathy is associated with aberrant O-glycosylation of IgA1, which is recognized by autoantibodies leading to the formation of circulating immune complexes. Some of them, after deposition into kidney mesangium, trigger glomerular injury. In patients with active disease nonresponding to angiotensin-converting enzyme inhibitors or angiotensin II blockers, corticosteroids are recommended. METHODS: The relationship between the corticosteroid therapy and serum levels of IgA, aberrantly O-glycosylated IgA1, IgA-containing immune complexes and their mesangioproliferative activity was analyzed in IgA nephropathy patients and disease and healthy controls. RESULTS: Prednisone therapy significantly reduced proteinuria and levels of serum IgA, galactose-deficient IgA1, and IgA-IgG immune complexes in IgA nephropathy patients and thus reduced differences in all of the above parameters between IgAN patients and control groups. A moderate but not significant reduction of mesangioproliferative potential of IgA-IgG immune complexes and IgA sialylation was detected. CONCLUSION: The prednisone therapy reduces overall aberrancy in IgA1 O-glycosylation in IgA nephropathy patients, but the measurement of IgA1 parameters does not allow us to predict the prednisone therapy outcome in individual patients.
BACKGROUND/AIMS: IgA nephropathy is associated with aberrant O-glycosylation of IgA1, which is recognized by autoantibodies leading to the formation of circulating immune complexes. Some of them, after deposition into kidney mesangium, trigger glomerular injury. In patients with active disease nonresponding to angiotensin-converting enzyme inhibitors or angiotensin II blockers, corticosteroids are recommended. METHODS: The relationship between the corticosteroid therapy and serum levels of IgA, aberrantly O-glycosylated IgA1, IgA-containing immune complexes and their mesangioproliferative activity was analyzed in IgA nephropathypatients and disease and healthy controls. RESULTS:Prednisone therapy significantly reduced proteinuria and levels of serum IgA, galactose-deficientIgA1, and IgA-IgG immune complexes in IgA nephropathypatients and thus reduced differences in all of the above parameters between IgAN patients and control groups. A moderate but not significant reduction of mesangioproliferative potential of IgA-IgG immune complexes and IgA sialylation was detected. CONCLUSION: The prednisone therapy reduces overall aberrancy in IgA1 O-glycosylation in IgA nephropathypatients, but the measurement of IgA1 parameters does not allow us to predict the prednisone therapy outcome in individual patients.
Authors: Katerina Zachova; Jana Jemelkova; Petr Kosztyu; Yukako Ohyama; Kazuo Takahashi; Josef Zadrazil; Jiri Orsag; Karel Matousovic; Dana Galuszkova; Nadezda Petejova; Jiri Mestecky; Milan Raska Journal: J Am Soc Nephrol Date: 2022-02-03 Impact factor: 14.978
Authors: Barbora Knoppova; Colin Reily; R Glenn King; Bruce A Julian; Jan Novak; Todd J Green Journal: J Clin Med Date: 2021-09-29 Impact factor: 4.241