Significance of glomerular activation of the alternative pathway and lectin pathway in lupus nephritis
Abstract
The objective of the present study was to elucidate the association between glomerular complement depositions belonging to the alternative (AP) and lectin (LP) pathways, and clinical findings of lupus nephritis (LN). Immunofluorescence (IF) was performed on 17 LN patients using antibodies against factor B, factor H, properdin, mannose-binding lectin (MBL) and L-ficolin. Compared with factor B/factor H negative patients (n = 9), positive patients (n = 8) showed longer duration of LN (p < 0.05) and more severe interstitial fibrosis (p < 0.05). Eleven patients had properdin deposition in glomeruli, and in three of them, with a duration of LN of less than 1 month, factor B was undetectable. Compared with properdin negative patients (n = 6), positive patients (n = 11) showed significantly higher urinary protein excretion (p < 0.01). MBL/L-ficolin positive patients (n = 11) also had significantly higher urinary protein excretion (p < 0.05) compared with negative patients (n = 6). An independent association was found between glomerular deposition of properdin and that of MBL/L-ficolin (p < 0.01) in addition to factor B/factor H. Traces of glomerular activation of AP and LP reflected the clinical status of LN. It appears that glomerular deposition of each complement component, especially properdin, may be an index of the histological activity of LN.
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References
1. Rothfield N, Ross HA, Minta JO, Lepow IH. Glomerular and dermal deposition of properdin in systemic lupus erythematosus. N Engl J Med 1972; 287: 681–685.
2. Wyatt RJ, McAdams AJ, Forristal J, Snyder J, West CD. Glomerular deposition of complement-control proteins in acute and chronic glomerulonephritis. Kidney Int 1979; 16: 505–512.
3. Lhotta K, Wuzner R, Konig P. Glomerular deposition of mannose-binding lectin in human glomerulonephritis. Nephrol Dial Transplant 1999; 14: 881–886.
4. Matsushita M, Endo Y, Fujita T. Complement-activating complex of ficolin and mannose-binding lectin-associated serine protease. J Immunol 2000; 164: 2281–2284.
5. Matsushita M, Kuraya M, Hamasaki N, Tsujimura M, Shiraki H, Fujita T. Activation of the lectin complement pathway by H-ficolin (Hakata antigen). J Immunol 2002; 168: 3502–3506.
6. Petersen SV, Thiel S, Jensenius JC. The mannan-binding lectin pathway of complement activation: biology and disease association. Mol Immunol 2001; 38: 133–149.
7. Holmskov U, Thiel S, Jensenius JC. Collectins and ficolins: humoral lectins of the innate immune defense. Annu Rev Immunol 2003; 21: 547–578.
8. Matsushita M, Fujita T. Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease. J Exp Med 1992; 76: 1497–1502.
9. Matsushita M, Fujita T. Cleavage of the third component of complement (C3) by mannose-binding protein associated serine protease (MASP) with subsequent complement activation. Immunobiol 1995; 194: 443–448.
10. Sato T, Endo Y, Matsushita M, Fujita T. Molecular characterization of a novel serine protease involved in activation of the complement system by mannose-binding protein. Int Immunol 1994; 6: 665–669.
11. Endo M, Ohi H, Ohsawa I, Fujita T, Matsushita M, Fujita T. Glomerular deposition of mannose-binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathy. Nephrol Dial Transplant 1998; 13: 1984–1990.
12. Lachmann PJ. The amplification loop of the complement pathways. Adv Immunol 2009; 104: 115–149.
13. Hourcade DE. The role of properdin in the assembly of the alternative pathway C3 convertases of complement. J Biol Chem 2006; 281: 2128–2132.
14. Kemper C, Mitchell LM, Zhang L, Hourcade DE. The complement protein properdin binds apoptotic T cells and promotes complement activation and phagocytosis. Proc Natl Acad Sci U S A 2008; 105: 9023–9028.
15. Spitzer D, Mitchell LM, Atkinson JP, Hourcade DE. Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. J Immunol 2007; 179: 2600–2608.
16. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725–1725.
17. Matsushita M, Endo Y, Taira S, et al. A novel human serum lectin with collagen- and fibrinogen-like domains that functions as an opsonin. J Biol Chem 1996; 271: 2448–2454.
18. Harboe M, Mollnes TE. The alternative complement pathway revisited. J Cell Mol Med 2008; 12: 1074–1084.
19. Xu W, Berger SP, Trouw LA, et al. Properdin binds to late apoptotic and necrotic cells independently of C3b and regulates alternative pathway complement activation. J Immunol 2008; 180: 7613–7621.
20. Sato N, Ohsawa I, Takagi M, et al. Type B insulin resistance syndrome with systemic lupus erythematosus. Clin Nephrol 2010; 73: 157–162.
21. Xing GQ, Chen M, Liu G, Zheng XJE, Zhao MH. Differential deposition of C4d and MBL in glomeruli of patients with ANCA-negative pauci-immune crescentic glomerulonephritis. J Clin Immunol 2010; 30: 144–156.
22. Seelen MA, Roos A, Daha MR. Role of complement in innate and autoimmunity. J Nephrol 2005; 18: 642–653.
23. Watanabe H, Garnier G, Circolo A, et al. Modulation of renal disease in MRL/lpr mice genetically deficient in the alternative complement pathway factor B. J Immunol 2000; 164: 786–794.
24. Nolan KF, Reid KB. Properdin. Methods Enzymol 1993; 223: 35–46.
25. Kohler PF, Muller-Eberhard HJ. Immunochemical quantitation of the third, fourth and fifth components of human complement: concentrations in the serum of healthy adults. J Immunol 1967; 99: 1211–1216.
26. Oglesby TJ, Ueda A, Volanakis JE. Radioassays for quantitation of intact complement proteins C2 and B in human serum. J Immunol Methods 1988; 110: 55–62.
27. Burton C, Harris KP. The role of proteinuria in the progression of chronic renal failure. Am J Kidney Dis 1996; 27: 765–775.
28. Tang S, Leung JC, Tsang AW, Lan HY, Chan TM, Lai KN. Transferrin up-regulates chemokine synthesis by human proximal tubular epithelial cells: implication on mechanism of tubuloglomerular communication in glomerulopathic proteinuria. Kidney Int 2002; 61: 1655–1665.
29. Nangaku M. Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure. Intern Med 2004; 43: 9–17.
30. Nangaku M, Pippin J, Couser WG. Complement membrane attack complex (C5b-9) mediates interstitial disease in experimental nephrotic syndrome. J Am Soc Nephrol 1999; 10: 2323–2331.
31. Siezenga MA, van der Geest RN, Mallat MJ, Rabelink TJ, Daha MR, Berger SP. Urinary properdin excretion is associated with internal complement activation and poor renal function. Nephrol Dial Transplant 2010; 25: 1157–1161.
32. Fadok VA, Henson PM. Apoptosis: giving phosphatidylserine recognition an assist–with a twist. Curr Biol 2003; 3: 655–657.
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Article first published online: September 5, 2011
Issue published: November 2011
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PubMed: 21893562
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