Proliferative Glomerulonephritis Secondary to Dysfunction of the Alternative Pathway of Complement
Tóm tắt
dense deposit disease (DDD) is the prototypical membranoproliferative glomerulonephritis (MPGN), in which fluid-phase dysregulation of the alternative pathway (AP) of complement results in the accumulation of complement debris in the glomeruli, often producing an MPGN pattern of injury in the absence of immune complexes. A recently described entity referred to as GN with C3 deposition (GN-C3) bears many similarities to DDD. The purpose of this study was to evaluate AP function in cases of GN-C3.
Five recent cases of MPGN with extensive C3 deposition were studied. Renal biopsy in one case exhibited the classic findings of DDD. Three cases showed GN-C3 in the absence of significant Ig deposition; however, the classic hallmark of DDD—dense deposits along the glomerular basement membranes and mesangium—was absent. The remaining case exhibited features of both DDD and GN-C3.
Evidence of AP activation was demonstrable in all cases and included increased levels of soluble membrane attack complex (all cases), positive AP functional assays (four cases), and a positive hemolytic assay (one case). Autoantibodies were found to C3 convertase (two cases) and to factor H (one case). Factor H mutation screening identified the
These studies implicate AP dysregulation in a spectrum of rare renal diseases that includes GN-C3 and DDD.
Từ khóa
Tài liệu tham khảo
Rennke, 1995, Secondary membranoproliferative glomerulonephritis, Kidney Int, 47, 643, 10.1038/ki.1995.82
Alpers, 2008, Cryoglobulinemia and renal disease, Curr Opin Nephrol Hypertens, 17, 243, 10.1097/MNH.0b013e3282f8afe2
Appel, 2005, Membranoproliferative glomerulonephritis type II (dense deposit disease): An update, J Am Soc Nephrol, 16, 1392, 10.1681/ASN.2005010078
Nasr, 2009, Dense deposit disease: Clinicopathologic study of 32 pediatric and adult patients, Clin J Am Soc Nephrol, 4, 22, 10.2215/CJN.03480708
Smith, 2007, New approaches to the treatment of dense deposit disease, J Am Soc Nephrol, 18, 2447, 10.1681/ASN.2007030356
Servais, 2007, Primary glomerulonephritis with isolated C3 deposits: A new entity which shares common genetic risk factors with haemolytic uraemic syndrome, J Med Genet, 44, 193, 10.1136/jmg.2006.045328
Habbig, 2009, C3 deposition glomerulopathy due to a functional Factor H defect, Kidney Int, 75, 1230, 10.1038/ki.2008.354
Fakhouri, 2010, C3 glomerulopathy: A new classification, Nat Rev Nephrol, 6, 494, 10.1038/nrneph.2010.85
Sethi, 2010, Dense deposit disease associated with monoclonal gammopathy of undetermined significance, Am J Kidney Dis, 56, 977, 10.1053/j.ajkd.2010.06.021
Sethi, 2009, Glomeruli of dense deposit disease contain components of the alternative and terminal complement pathway, Kidney Int, 75, 952, 10.1038/ki.2008.657
Vrana, 2009, Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens, Blood, 114, 4957, 10.1182/blood-2009-07-230722
Choi, 1990, Incorporation of SP-40,40 into the soluble membrane attack complex (SMAC, SC5b-9) of complement, Int Immunol, 2, 413, 10.1093/intimm/2.5.413
Nesvizhskii, 2003, A statistical model for identifying proteins by tandem mass spectrometry, Anal Chem, 75, 4646, 10.1021/ac0341261
Zipfel, 2009, Complement regulators and inhibitory proteins, Nat Rev Immunol, 9, 729, 10.1038/nri2620
Abrera-Abeleda, 2006, Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease), J Medl Genet, 43, 582, 10.1136/jmg.2005.038315
Skerka, 2007, Defective complement control of Factor H (Y402H) and FHL-1 in age-related macular degeneration, Molec Immunol, 44, 3398, 10.1016/j.molimm.2007.02.012
Trendelenburg, 2005, The role of complement in cryoglobulin-induced immune complex glomerulonephritis, J Immunol, 175, 6909, 10.4049/jimmunol.175.10.6909
Yamabe, 1995, Hepatitis C virus infection and membranoproliferative glomerulonephritis in Japan, J Am Soc Nephrol, 6, 220, 10.1681/ASN.V62220
Vella, 1995, Glomerulonephritis after ventriculo-atrial shunt, QJM, 88, 911
Hulton, 1992, Mesangiocapillary glomerulonephritis associated with meningococcal meningitis, C3 nephritic factor and persistently low complement C3 and C5, Pediatr Nephrol, 6, 239, 10.1007/BF00878356
Boseman, 2008, Marfan syndrome, MPGN, and bacterial endocarditis, Am J Kidney Dis, 51, 697, 10.1053/j.ajkd.2007.08.031
Weening, 2004, The classification of glomerulonephritis in systemic lupus erythematosus revisited, Kidney Int, 65, 521, 10.1111/j.1523-1755.2004.00443.x
Adam, 2006, Acute renal failure due to mesangial proliferative glomerulonephritis in a pregnant woman with primary Sjögren's syndrome, Clin Rheumatol, 25, 75, 10.1007/s10067-005-1131-8