Complement Regulatory Proteins in Kidneys of Patients with Anti-neutrophil Cytoplasmic Antibody (ANCA)-associated Vasculitis

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2017 Sep 24

PMID 28940198

Citations 8

Authors

L Cheng

S-J Gou

H-Y Qiu

L Ma

P Fu

Affiliations

Soon will be listed here.

Abstract

The complement system activation is involved in the development of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). The study aimed to investigate the expression of complement regulatory proteins (CRPs) CD46, CD55 and CD59 in kidneys of 51 AVV patients. The expression of CD46, CD55 and CD59 in kidneys was detected by immunohistochemistry and double immunofluorescence staining. The immunohistochemical examination revealed that expression of the three CRPs could be detected in the glomeruli and tubules of both AAV patients and normal controls. The expression levels of the three CRPs in glomeruli of patients with AAV were significantly lower than those of normal controls. The scores of CD46 and CD55 expression in the tubules of AAV patients were significantly lower than those of normal controls, while there was no significant difference between the scores of CD59 expression in tubules of AAV patients and those of normal controls. Among AAV patients, the expression level of CD46 in glomeruli correlated inversely with the proportion of normal glomeruli, while it correlated with tubular atrophy in renal interstitium (r = -0·305, P = 0·026; r = 0·330, P = 0·023, respectively). The expression levels of CD55 and CD59 in glomeruli correlated with the proportion of total crescents (r = 0·384, P = 0·006; r = 0·351, P = 0·011, respectively). Double immunofluorescence staining indicated that all three CRPs were expressed on endothelial cells, podocytes and mesangial cells in glomeruli. The expression levels of the three CRPs were dysregulated in kidneys of patients with AAV. The expression levels of CD46, CD55 and CD59 were associated with the severity of renal injury of AAV patients.

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References

Bajema I, Hagen E, Hansen B, Hermans J, Noel L, Waldherr R . The renal histopathology in systemic vasculitis: an international survey study of inter- and intra-observer agreement. Nephrol Dial Transplant. 1996; 11(10):1989-95. DOI: 10.1093/oxfordjournals.ndt.a027086. View

Endoh M, Yamashina M, Ohi H, Funahashi K, Ikuno T, Yasugi T . Immunohistochemical demonstration of membrane cofactor protein (MCP) of complement in normal and diseased kidney tissues. Clin Exp Immunol. 1993; 94(1):182-8. PMC: 1534360. DOI: 10.1111/j.1365-2249.1993.tb05998.x. View

Nielsen J, McNagny K . The role of podocalyxin in health and disease. J Am Soc Nephrol. 2009; 20(8):1669-76. DOI: 10.1681/ASN.2008070782. View

Oglesby T, Allen C, Liszewski M, White D, Atkinson J . Membrane cofactor protein (CD46) protects cells from complement-mediated attack by an intrinsic mechanism. J Exp Med. 1992; 175(6):1547-51. PMC: 2119264. DOI: 10.1084/jem.175.6.1547. View

Sarrab R, Lennon R, Ni L, Wherlock M, Welsh G, Saleem M . Establishment of conditionally immortalized human glomerular mesangial cells in culture, with unique migratory properties. Am J Physiol Renal Physiol. 2011; 301(5):F1131-8. PMC: 3213908. DOI: 10.1152/ajprenal.00589.2010. View

Shang Y, Chai N, Gu Y, Ding L, Yang Y, Zhou J . Systematic immunohistochemical analysis of the expression of CD46, CD55, and CD59 in colon cancer. Arch Pathol Lab Med. 2014; 138(7):910-9. DOI: 10.5858/arpa.2013-0064-OA. View

Falk R, Terrell R, Charles L, Jennette J . Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci U S A. 1990; 87(11):4115-9. PMC: 54058. DOI: 10.1073/pnas.87.11.4115. View

Segelmark M, Wieslander J . IgG subclasses of antineutrophil cytoplasm autoantibodies (ANCA). Nephrol Dial Transplant. 1993; 8(8):696-702. DOI: 10.1093/ndt/8.8.696. View

Morgan B . Isolation and characterization of the complement-inhibiting protein CD59 antigen from platelet membranes. Biochem J. 1992; 282 ( Pt 2):409-13. PMC: 1130793. DOI: 10.1042/bj2820409. View

10.

Xiao H, Schreiber A, Heeringa P, Falk R, Jennette J . Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am J Pathol. 2007; 170(1):52-64. PMC: 1762697. DOI: 10.2353/ajpath.2007.060573. View

11.

Jennette J, Falk R, Bacon P, Basu N, Cid M, Ferrario F . 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2012; 65(1):1-11. DOI: 10.1002/art.37715. View

12.

Hauer H, Bajema I, van Houwelingen H, Ferrario F, Noel L, Waldherr R . Renal histology in ANCA-associated vasculitis: differences between diagnostic and serologic subgroups. Kidney Int. 2002; 61(1):80-9. DOI: 10.1046/j.1523-1755.2002.00089.x. View

13.

Sethi S, Zand L, De Vriese A, Specks U, Vrana J, Kanwar S . Complement activation in pauci-immune necrotizing and crescentic glomerulonephritis: results of a proteomic analysis. Nephrol Dial Transplant. 2017; 32(suppl_1):i139-i145. DOI: 10.1093/ndt/gfw299. View

14.

Luqmani R, Bacon P, Moots R, Janssen B, Pall A, Emery P . Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM. 1994; 87(11):671-8. View

15.

Davies A, LACHMANN P . Membrane defence against complement lysis: the structure and biological properties of CD59. Immunol Res. 1993; 12(3):258-75. DOI: 10.1007/BF02918257. View

16.

Gou S, Yuan J, Chen M, Yu F, Zhao M . Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int. 2012; 83(1):129-37. DOI: 10.1038/ki.2012.313. View

17.

Hilhorst M, van Paassen P, van Rie H, Bijnens N, Heerings-Rewinkel P, van Breda Vriesman P . Complement in ANCA-associated glomerulonephritis. Nephrol Dial Transplant. 2015; 32(8):1302-1313. DOI: 10.1093/ndt/gfv288. View

18.

Nicholson-Weller A, Wang C . Structure and function of decay accelerating factor CD55. J Lab Clin Med. 1994; 123(4):485-91. View

19.

Thurman J, Renner B . Dynamic control of the complement system by modulated expression of regulatory proteins. Lab Invest. 2010; 91(1):4-11. PMC: 3109904. DOI: 10.1038/labinvest.2010.173. View

20.

Chen M, Xing G, Yu F, Liu G, Zhao M . Complement deposition in renal histopathology of patients with ANCA-associated pauci-immune glomerulonephritis. Nephrol Dial Transplant. 2008; 24(4):1247-52. DOI: 10.1093/ndt/gfn586. View