Significance of glomerular activation of the alternative pathway and lectin pathway in lupus nephritis

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.

[1]  T. Rabelink,et al.  Urinary properdin excretion is associated with intrarenal complement activation and poor renal function. , 2010, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[2]  Y. Tomino,et al.  Type B insulin resistance syndrome with systemic lupus erythematosus. , 2010, Clinical nephrology.

[3]  D. Hourcade,et al.  The complement protein properdin binds apoptotic T cells and promotes complement activation and phagocytosis , 2008, Proceedings of the National Academy of Sciences.

[4]  L. Trouw,et al.  Properdin Binds to Late Apoptotic and Necrotic Cells Independently of C3b and Regulates Alternative Pathway Complement Activation12 , 2008, The Journal of Immunology.

[5]  M. Harboe,et al.  The alternative complement pathway revisited , 2008, Journal of cellular and molecular medicine.

[6]  D. Hourcade,et al.  Properdin Can Initiate Complement Activation by Binding Specific Target Surfaces and Providing a Platform for De Novo Convertase Assembly1 , 2007, The Journal of Immunology.

[7]  D. Hourcade.  The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement* , 2006, Journal of Biological Chemistry.

[8]  M. Daha,et al.  Role of complement in innate and autoimmunity. , 2005, Journal of nephrology.

[9]  S. Thiel,et al.  Collections and ficolins: humoral lectins of the innate immune defense. , 2003, Annual review of immunology.

[10]  V. Fadok,et al.  Apoptosis: giving phosphatidylserine recognition an assist – with a twist , 2003, Current Biology.

[11]  T. Chan,et al.  Transferrin up-regulates chemokine synthesis by human proximal tubular epithelial cells: implication on mechanism of tubuloglomerular communication in glomerulopathic proteinura. , 2002, Kidney international.

[12]  T. Fujita,et al.  Activation of the Lectin Complement Pathway by H-Ficolin (Hakata Antigen)1 , 2002, The Journal of Immunology.

[13]  S. Thiel,et al.  The mannan-binding lectin pathway of complement activation: biology and disease association. , 2001, Molecular immunology.

[14]  T. Fujita,et al.  Cutting Edge: Complement-Activating Complex of Ficolin and Mannose-Binding Lectin-Associated Serine Protease1 , 2000, The Journal of Immunology.

[15]  H. Colten,et al.  Modulation of Renal Disease in MRL/lpr Mice Genetically Deficient in the Alternative Complement Pathway Factor B1 , 2000, The Journal of Immunology.

[16]  M. Nangaku,et al.  Complement membrane attack complex (C5b-9) mediates interstitial disease in experimental nephrotic syndrome. , 1999, Journal of the American Society of Nephrology : JASN.

[17]  R. Würzner,et al.  Glomerular deposition of mannose-binding lectin in human glomerulonephritis. , 1999, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[18]  T. Fujita,et al.  Glomerular deposition of mannose-binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathy. , 1998, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[19]  M. Hochberg,et al.  Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. , 1997, Arthritis and rheumatism.

[20]  K. Harris,et al.  The role of proteinuria in the progression of chronic renal failure. , 1996, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[21]  T. Fujita,et al.  A Novel Human Serum Lectin with Collagen- and Fibrinogen-like Domains That Functions as an Opsonin (*) , 1996, The Journal of Biological Chemistry.

[22]  T. Fujita,et al.  Cleavage of the third component of complement (C3) by mannose-binding protein-associated serine protease (MASP) with subsequent complement activation. , 1995, Immunobiology.

[23]  T. Fujita,et al.  Molecular characterization of a novel serine protease involved in activation of the complement system by mannose-binding protein. , 1994, International immunology.

[24]  T. Fujita,et al.  Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease , 1992, The Journal of experimental medicine.

[25]  J. Volanakis,et al.  Radioassays for quantitation of intact complement proteins C2 and B in human serum. , 1988, Journal of immunological methods.

[26]  A. J. Mcadams,et al.  Glomerular deposition of complement-control proteins in acute and chronic glomerulonephritis. , 1979, Kidney international.

[27]  J. Minta,et al.  Glomerular and dermal depostion of properdin in systemic lupus erythematosus. , 1972, The New England journal of medicine.

[28]  H. Müller-Eberhard,et al.  Immunochemical quantitation of the third, fourth and fifth components of human complement: concentrations in the serum of healthy adults. , 1967, Journal of immunology.

[29]  Min Chen,et al.  Differential Deposition of C4d and MBL in Glomeruli of Patients with ANCA-Negative Pauci-Immune Crescentic Glomerulonephritis , 2009, Journal of Clinical Immunology.

[30]  P. Lachmann.  The amplification loop of the complement pathways. , 2009, Advances in immunology.

[31]  M. Nangaku.  Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure. , 2004, Internal medicine.