期刊论文详细信息
BMC Nephrology
Serum levels and renal deposition of C1q complement component and its antibodies reflect disease activity of lupus nephritis
Ming-hui Zhao2  Feng Yu2  Li-hua Wu1  Di Song2  Ying Tan2 
[1] Department of Nephrology, General Hospital of Ningxia Medical University, Ningxia 750004, Peoples’ Republic of China;Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing 100034, Peoples’ Republic of China
关键词: C1q depostion;    Serum levels of C1q;    Anti-C1q autoantibodies;    Lupus nephritis;   
Others  :  1082976
DOI  :  10.1186/1471-2369-14-63
 received in 2012-10-07, accepted in 2013-03-14,  发布年份 2013
PDF
【 摘 要 】

Background

Lupus nephritis is considered to be a principal cause of morbidity and mortality in SLE. Few studies focus on the association between anti-C1q antibodies in circulation and renal C1q deposition in human lupus nephritis. In this study, we detected the serum levels of C1q, presence of anti-C1q antibodies in circulation, renal C1q deposition and further analyzed their associations with clinical and pathological activity in a large cohort of Chinese lupus nephritis patients.

Methods

Sera and renal biopsies from 218 consecutive patients with lupus nephritis with long-term follow up data were studied. Sera were tested for levels of C1q and anti-C1q autoantibodies. Associations of levels of C1q, anti-C1q autoantibodies with renal deposition of C1q, clinical and histopathological data and renal outcome were further investigated.

Results

The levels of serum C1q were significantly lower in lupus nephritis than that in normal controls [33.81 ± 20.36 v.s. 61.97 ± 10.50 μg/ml (P < 0.001)]. The prevalence of anti-C1q antibodies, ratios of glomerular and vascular deposition of C1q in patients with lupus nephritis were 42.7% (93/218), 71.6% (156/218) and 86.2% (188/218), respectively. The serum C1q levels and anti-C1q antibodies were associated with SLEDAI scores (P < 0.001, P = 0.012, respectively), renal total activity indices scores (P < 0.001, P < 0.001, respectively). Granular positive staining of C1q and IgG by immunofluorescence was co-localized almost completely along the glomerular capillary wall and mesangial areas. Patients with anti-C1q antibodies presented with significantly lower serum C1q levels than those without it (23.82 [0.60, 69.62] μg/ml v.s. 37.36 [0.64, 82.83] μg/ml, P < 0.001). The presence of anti-C1q antibodies was associated with the presence of glomerular C1q deposition (P < 0.001), but not with the presence of renal vascular C1q deposition (P = 0.203).

Conclusion

Anti-C1q autoantibodies were closely associated with serum levels of C1q and glomerular deposition of C1q. Kidney is at least one of the target organs of anti-C1q autoantibodies.

【 授权许可】

   
2013 Tan et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20141224191821736.pdf 1754KB PDF download
Figure 3. 68KB Image download
Figure 2. 58KB Image download
Figure 1. 192KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】
  • [1]Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, Mejia JC, Aydintug AO, Chwalinska-Sadowska H, de Ramon E: Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 2003, 82:299-308.
  • [2]Son M, Santiago-Schwarz F, Al-Abed Y, Diamond B: C1q limits dendritic cell differentiation and activation by engaging LAIR-1. Proc Natl Acad Sci U S A 2012, 109:E3160-E3167.
  • [3]Lood C, Gullstrand B, Truedsson L, Olin AI, Alm GV, Ronnblom L, Sturfelt G, Eloranta ML, Bengtsson AA: C1q inhibits immune complex-induced interferon-alpha production in plasmacytoid dendritic cells: a novel link between C1q deficiency and systemic lupus erythematosus pathogenesis. Arthritis Rheum 2009, 60:3081-3090.
  • [4]Elkon KB, Santer DM: Complement, interferon and lupus. Curr Opin Immunol 2012, 24:665-670.
  • [5]Kallel-Sellami M, Baili-Klila L, Zerzeri Y, Laadhar L, Blouin J, Abdelmoula MS, Zitouni M, Fremeaux-Bacchi V, Ben Dridi MF, Makni S: Pediatric systemic lupus erythematosus with C1q deficiency. Ann N Y Acad Sci 2007, 1108:193-196.
  • [6]Greisman SG, Redecha PB, Kimberly RP, Christian CL: Differences among immune complexes: association of C1q in SLE immune complexes with renal disease. J Immunol 1987, 138:739-745.
  • [7]Fang QY, Yu F, Tan Y, Xu LX, Wu LH, Liu G, Shao FM, Zhao MH: Anti-C1q antibodies and IgG subclass distribution in sera from Chinese patients with lupus nephritis. Nephrol Dial Transplant 2009, 24:172-178.
  • [8]Marto N, Bertolaccini ML, Calabuig E, Hughes GR, Khamashta MA: Anti-C1q antibodies in nephritis: correlation between titres and renal disease activity and positive predictive value in systemic lupus erythematosus. Ann Rheum Dis 2005, 64:444-448.
  • [9]Trouw LA, Seelen MA, Duijs JM, Benediktsson H, Van Kooten C, Daha MR: Glomerular deposition of C1q and anti-C1q antibodies in mice following injection of antimouse C1q antibodies. Clin Exp Immunol 2003, 132:32-39.
  • [10]Trouw LA, Duijs JM, van Kooten C, Daha MR: Immune deposition of C1q and anti-C1q antibodies in the kidney is dependent on the presence of glomerular IgG. Mol Immunol 2003, 40:595-602.
  • [11]Trouw LA, Seelen MA, Visseren R, Duijs JM, Benediktsson H, de Heer E, Roos A, van Kooten C, Daha MR: Anti-C1q autoantibodies in murine lupus nephritis. Clin Exp Immunol 2004, 135:41-48.
  • [12]Trouw LA, Groeneveld TW, Seelen MA, Duijs JM, Bajema IM, Prins FA, Kishore U, Salant DJ, Verbeek JS, van Kooten C, Daha MR: Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes. J Clin Invest 2004, 114:679-688.
  • [13]Hochberg MC: Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997, 40:1725.
  • [14]Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH: Derivation of the SLEDAI. A disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum 1992, 35:630-640.
  • [15]Yu F, Tan Y, Liu G, Wang SX, Zou WZ, Zhao MH: Clinicopathological characteristics and outcomes of patients with crescentic lupus nephritis. Kidney Int 2009, 76:307-317.
  • [16]Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JA, Cook T, Ferrario F: The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004, 15:241-250.
  • [17]Austin HA 3rd, Muenz LR, Joyce KM, Antonovych TT, Balow JE: Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome. Kidney Int 1984, 25:689-695.
  • [18]Nascimento EJ, Silva AM, Cordeiro MT, Brito CA, Gil LH, Braga-Neto U, Marques ET: Alternative complement pathway deregulation is correlated with dengue severity. PLoS One 2009, 4:e6782.
  • [19]Katsumata Y, Miyake K, Kawaguchi Y, Okamoto Y, Kawamoto M, Gono T, Baba S, Hara M, Yamanaka H: Anti-C1q antibodies are associated with systemic lupus erythematosus global activity but not specifically with nephritis: a controlled study of 126 consecutive patients. Arthritis Rheum 2011, 63:2436-2444.
  • [20]Horak P, Hermanova Z, Zadrazil J, Ciferska H, Ordeltova M, Kusa L, Zurek M, Tichy T: C1q complement component and -antibodies reflect SLE activity and kidney involvement. Clin Rheumatol 2006, 25:532-536.
  • [21]Chen Z, Wang GS, Wang GH, Li XP: Anti-C1q antibody is a valuable biological marker for prediction of renal pathological characteristics in lupus nephritis. Clin Rheumatol 2012, 31:1323-1329.
  • [22]Uwatoko S, Mannik M: Low-molecular weight C1q-binding immunoglobulin G in patients with systemic lupus erythematosus consists of autoantibodies to the collagen-like region of C1q. J Clin Invest 1988, 82:816-824.
  • [23]Bulla R, Agostinis C, Bossi F, Rizzi L, Debeus A, Tripodo C, Radillo O, De Seta F, Ghebrehiwet B, Tedesco F: Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium. Mol Immunol 2008, 45:2629-2640.
  • [24]Ghebrehiwet B, Hosszu KK, Valentino A, Peerschke EI: The C1q family of proteins: insights into the emerging non-traditional functions. Front Immunol 2012, 3:52.
  • [25]Nauta AJ, Castellano G, Xu W, Woltman AM, Borrias MC, Daha MR, van Kooten C, Roos A: Opsonization with C1q and mannose-binding lectin targets apoptotic cells to dendritic cells. J Immunol 2004, 173:3044-3050.
  • [26]Krishnan MR, Wang C, Marion TN: Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice. Kidney Int 2012, 82:184-192.
  • [27]Sjowall C, Zickert A, Skogh T, Wettero J, Gunnarsson I: Serum levels of autoantibodies against C-reactive protein correlate with renal disease activity and response to therapy in lupus nephritis. Arthritis Res Ther 2009, 11:R188. BioMed Central Full Text
  • [28]Doria A, Zen M, Canova M, Bettio S, Bassi N, Nalotto L, Rampudda M, Ghirardello A, Iaccarino L: SLE diagnosis and treatment: when early is early. Autoimmun Rev 2010, 10:55-60.
  • [29]Nauta AJ, Bottazzi B, Mantovani A, Salvatori G, Kishore U, Schwaeble WJ, Gingras AR, Tzima S, Vivanco F, Egido J: Biochemical and functional characterization of the interaction between pentraxin 3 and C1q. Eur J Immunol 2003, 33:465-473.
  • [30]Tan Y, Yu F, Qu Z, Su T, Xing GQ, Wu LH, Wang FM, Liu G, Yang L, Zhao MH: Modified C-reactive protein might be a target autoantigen of TINU syndrome. Clin J Am Soc Nephrol 2011, 6:93-100.
  • [31]Manfredi AA, Rovere-Querini P, Bottazzi B, Garlanda C, Mantovani A: Pentraxins, humoral innate immunity and tissue injury. Curr Opin Immunol 2008, 20:538-544.
  文献评价指标  
  下载次数:20次 浏览次数:0次