Abstract
Background
Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis is commonly classified as pauci-immune glomerulonephritis; however, some cases have granular immunoglobulin deposition along the glomerular capillary. The pathogenesis of immune deposits is poorly studied.
Methods
Of 66 patients diagnosed with ANCA-associated glomerulonephritis on renal biopsy, cases with immunoglobulin deposition along the glomerular capillary were identified and their clinicopathological characteristics were analyzed. We also performed myeloperoxidase (MPO) and double immunofluorescence (IF) stainings to determine the presence of immune complex antigens.
Results
Granular IgG deposition, IgG plus IgM deposition, and IgM deposition were observed in 15 (22.1%), 8 (11.2%), and 17 (25.0%) cases, respectively. In cases with granular IgG deposition, MPO-IgG double IF staining revealed co-localization of MPO and IgG. In cases with granular IgM deposition, MPO-IgM double IF staining did not co-localize. By electron microscopy, subepithelial deposition as well as intramembranous, subendothelial, and mesangial deposition was detected in the patients with IgG deposition. In addition, renal survival curves were not significantly different between the immunoglobulin deposition and non-deposition groups.
Conclusions
Granular IgG and/or IgM deposition was observed in 60.6% of patients with ANCA-associated glomerulonephritis. In cases with IgG deposition, electron-dense deposits (EDDs) were observed at various sites in the glomerulus, and MPO and IgG immunocomplex deposition was frequently observed along the glomerular capillary. With IgM deposition, EDDs were not obvious in the glomerular basement membrane, and MPO and IgM immunocomplex was not detected. These data suggest differential mechanism between IgG deposition and IgM deposition.
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References
van der Woude FJ, Rasmussen N, Lobatto S, Wiik A, Permin H, van Es LA, van der Giessen M, van der Hem GK, The TH. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener’s granulomatosis. Lancet. 1985;8426:425–9.
Falk RJ, Jennette JC. Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med. 1988;318(25):1651–7.
Ronco P, Verroust P, Mignon F, Kourilsky O, Vanhille P, Meyrier A, Mery JP, Morel-Maroger L. Immunopathological studies of polyarteritis nodosa and Wegener’s Granulomatosis: a Report of 43 Patients with 51 renal biopsies. Q J Med. 1983;52(206):212–23.
Neumann I, Regele H, Kain R, Birck R, Meisl FT. Glomerular immune deposits are associated with increased proteinuria in patients with ANCA-associated crescentic nephritis. Nephrol Dial Transpl. 2003;18:524–31.
Haas M, Eustace JA. Immune complex deposits in ANCA-associated crescentic glomerulonephritis: a study of 126 cases. Kidney Int. 2004;65:2145–52.
Savage CO, Winearls CG, Evans DJ, Rees AJ, Lockwood CM. Microscopic polyarteritis: presentation, pathology and prognosis. Q J Med. 1985;56(220):467–83.
Tse WY, Howie AJ, Adu D, Savage CO, Richards NT, Wheeler DC, Michael J. Association of vasculitic glomerulonephritis with membranous nephropathy: a report of 10 cases. Nephrol Dial Transplant. 1997;12(5):1017–27.
Gaber LW, Wall BM, Cooke CR. Coexistence of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis and membranous glomerulopathy. Am J Clin Pathol. 1993;99(2):211–5.
Hanamura K, Tojo A, Kinugasa S, Asaba K, Onozato ML, Uozaki H, Fukayama M, Fujita T. Detection of myeloperoxidase in membranous nephropathy-like deposits in patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. Hum Pathol. 2011;42:649–58.
Brouwer E, Huitema MG, Klok PA, de Weerd H, Tervaert JW, Weening JJ, Kallenberg CG. Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model. J Ex Med. 1993;177:905–14.
Flossmann O, Bacon P, de Groot K, Jayne D, Rasmussen N, Seo P, Westman K, Luqmani R. Development of comprehensive disease assessment in systemic vasculitis. Ann Rheum Dis. 2007;66(3):283–928.
Jennette JC. Rapidly progressive crescentic glomerulonephritis. Kidney Int. 2003;63:1164–77.
Harris AA, Falk RJ, Jennette JC. Crescentic glomerulonephritis with a paucity of glomerular immunoglobulin localization. Am J Kidney Dis. 1998;32:179–84.
Shimada M, Fujita T, Nakamura N, Narita I, Shimaya Y, Murakami R. A case of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis and concurrent membranous nephropathy. BMC Nephrol. 2013;14(73):1.
Morizane R, Konishi K, Hashiguchi A, Tokuyama H, Wakino S, Kawabe H, Hayashi M, Hayashi K, Itoh H. MPO-ANCA associated crescentic glomerulonephritis with numerous immune complexes: case report. BMC Nephrol. 2012;13:32.
Suwabe T, Ubara Y, Tagami T, Sawa N, Hoshino J, Katori H, Takemoto F, Hara S, Aita K, Hara S, Takaichi K. Membranous glomerulopathy induced by myeloperoxidase-anti-neutrophil cytoplasmic antibody-related crescentic glomerulonephritis. Intern Med. 2005;33:853–8.
Nasr SH, Said SM, Valeri AM, Stokes MB, Masani NN, D’Agati VD, Markowitz GS. Membranous glomerulonephritis with ANCA-associated necrotizing and crescentic glomerulonephritis. Clin J Am Soc Nephrol. 2009;4:299–308.
Kawashima S, Arimura Y, Sano K, Kudo A, Komagata Y, Kaname S, Kawakami H, Yamada A. Immunopathologic co-localization of MPO, IgG, and C3 in glomeruli in human MPO-ANCA-associated glomerulonephritis. Clin Nephrol. 2013;79(4):292–301.
Kessenbrock K, Krumbholz M, Schönermarck U, Back W, Gross WL, Werb Z, Gröne HJ, Brinkmann V, Jenne DE. Netting neutrophil in autoimmune small-vessel vasculitis. Nat Med. 2009;15(6):623–5.
Yu F, Chen M, Wang SX, Zou WZ, Zhao MH, Wang HY. Clinical and pathological characteristics and outcome of Chinese patients with primary anti-neutrophil cytoplasmic antibodies-associated systemic vasculitis with immune complex deposition in kidney. Nephrology. 2007;12:74–80.
Acknowledgements
The authors thank Minako Koike (Tokyo Women’s University Yachiyo Medical Center), Jun Ino (Toda Chuo General Hospital), and Michihiro Mitobe (Saiseikai Kurihashi Hospital), who performed renal biopsy and provided patient follow-up data. The authors thank Shigeru Horita (Tokyo Women's Medical University) for histological support.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number #3556) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent for renal biopsy was obtained from all individual participants included in the study.
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Hirose, O., Itabashi, M., Takei, T. et al. Antineutrophil cytoplasmic antibody-associated glomerulonephritis with immunoglobulin deposition. Clin Exp Nephrol 21, 643–650 (2017). https://doi.org/10.1007/s10157-016-1341-1
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DOI: https://doi.org/10.1007/s10157-016-1341-1