1、C-reactive protein & systemic lupus erythematosusContentC-reactive protein Synthesis of CRP Protein structure CRP ligand Anti-inflammatory effectSLECRP & SLE CRP CRP antibody IFN- NZBxNZW F1 murine lupus models CRP & pDC SummaryReference C-reactive protein(CRP)Acute phase proteinTillet and Francis d

2、iscovered in 1930C polysaccharide of the bacteria wallUsed to: 1. Detect acute infection 2. Assess the response to treatment 3. Evaluate response in chronic disease 4. Indicator of mild inflammation Synthesis of CRPProtein structureCRP ligandAnti-inflammatory CRPFcRIIbFcRIIL-10 & IL-1RAIL-12Anti-inf

3、lammatoryApoptotic vesicles or substance released by the vesiclesAutoantigenSLESystemic Lupus ErythematosusUnpredictable, incurableT cell , Ts cell function , B cellIC in skin, blood vessels, liver, kidney et al CRP and Autoimmune diseaseSLECRP may have a protective roleIn SLE, CRP failsReduced leve

4、ls of CRP SLEIL-6，IL-1，TNFSLE controlSLE incomplete lupus normal controlsSLE + arthritis, antibody Incomplete lupus progressed to SLE not prefressedJung J Y, Koh B R, Kim H A, et al. Autoantibodies to C-Reactive Protein in Incomplete Lupus and Systemic Lupus ErythematosusJ. Journal of Investigative

5、Medicine, 2014, 62(6): 890-893.Anti-CRP antibodies were detected in 26% of SLE patients.Anti-dsDNA positivity 32.7% in anti-CRPpositives 16% in anti-CRPnegativesSLEDAI scores anti-CRPpositive anti-CRPnegativeCorrelation: anti-CRPantibodies & anti-dsDNA antibodies.Pradhan V, Rajadhyaksha A, Yadav K,

6、et al. Anti-C reactive protein antibodies in Indian patients with systemic lupus erythematosusJ. Indian journal of nephrology, 2013, 23(6): 434.IL-6 & IL-1 CRP lowINF via (C/EBPs) and and STAT 3 inhibits CRP inductionSerum IFN levels are high during periods of lupus activity.Ronnblom L, Alm GV, Elor

7、anta ML. Type I interferon and lupus. Curr Opin Rheumatol 2009;21:4717.IFNInjected with: CRP& chromatin- coated latex beads Chromatin-coated latex beads Latex beads(control group)Result: CRP& chromatin-coated latex beads group had the highest median survival age. Chromatin-coated latex beads group h

8、ad the lowest median survival age.Du Clos TW, Zlock LT, Hicks PS and Mold C. Decreased autoantibody levels and enhanced survival of (Nzb X Nzw) F1 mice treated with C-reactive protein. Clinical Immunol Immunopathol 1994;70:22-27.（NZBxNZW）F1 murine lupus models (NZB/NZW) F1 mice with hCRPtg delay: Au

9、toimmune glomerulonephritis DeathExplanation: It prevent glomerular and extra-glomerular deposition of immune complexes, and/or enhanced phagocytosis of immune complexes by mesangial cells.Szalai AJ, Weaver CT, McCrory MA, et al. Delayed lupus onset in (Nzb X Nzw)F1 mice expressing a human C-reactiv

10、e protein transgene. Arthritis Rheum. 2003;48:1602-1611.200 g human-derived CRP improved renal function survival CRP delay proteinuria reverse ongoing proteinuria prevent & reverse accelerated NTNIL-10 dependent anti-inflammatory processRodriguez W, Mold C, Kataranovski M, Hutt J, Marnell LL and Du

11、Clos TW. Reversal of ongoing proteinuria in autoimmune mice by treatment with C-reactive protein. Arthritis Rheum. 2005;52(2):642-650.CRP inhibit pDC response to ICNucleoprotein autoantigen pDC CRPType I IFN DiseaseSummaryCRPgeneral markerIL-1& IL-6 induce synthesisCRP ligandAnti-inflammatory effect

12、CRP antibody & SLECRP effect & SLEIFN CRP & pDCReferenceJung J Y, Koh B R, Kim H A, et al. Autoantibodies to C-Reactive Protein in Incomplete Lupus and Systemic Lupus ErythematosusJ. Journal of Investigative Medicine, 2014, 62(6): 890-893.Eudy A M, Vines A I, Dooley M A, et al. Elevated C-reactive p

13、rotein and self-reported disease activity in systemic lupus erythematosusJ. Lupus, 2014, 23(14): 1460-1467.Song G G, Bae S C, Lee Y H. Diagnostic accuracies of procalcitonin and C-reactive protein for bacterial infection in patients with systemic rheumatic diseases: a meta-analysisJ. Clinical and ex

14、perimental rheumatology, 2014, 33(2): 166-173.Enocsson H, Sjwall C, Kastbom A, et al. Association of Serum CReactive Protein Levels With Lupus Disease Activity in the Absence of Measurable Interferon and a CReactive Protein Gene VariantJ. Arthritis & Rheumatology, 2014, 66(6): 1568-1573.Pradhan V, R

15、ajadhyaksha A, Yadav K, et al. Anti-C reactive protein antibodies in Indian patients with systemic lupus erythematosusJ. Indian journal of nephrology, 2013, 23(6): 434.Mold C, Clos T W D. CReactive Protein Inhibits Plasmacytoid Dendritic Cell Interferon Responses to Autoantibody Immune ComplexesJ. A

16、rthritis & Rheumatism, 2013, 65(7): 1891-1901.Sjwall C, Olin A I, Skogh T, et al. C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritisJ. Autoimmunity, 2013, 46(3): 205-214.Rezaieyazdi Z, Sahebari M, Hatef M R, et al. Is there any c

17、orrelation between high sensitive CRP and disease activity in systemic lupus erythematosus?J. Lupus, 2011, 20(14): 1494-1500.Meyer O. Anti-CRP antibodies in systemic lupus erythematosusJ. Joint Bone Spine, 2010, 77(5): 384-389.Ronnblom L, Alm GV, Eloranta ML. Type I interferon and lupus. Curr Opin R

18、heumatol 2009;21:4717.Figueredo MA, Rodriguez A, Ruiz-Yague M, et al. Autoantibodies against c-reactive protein: Clinical associations in systemic lupus erythematosus and primary antiphospholipid syndrome. J Rheumatol 2006;33:1980-1986.de Carvalho J F, Hanaoka B, Szyper-Kravitz M, et al. C-Reactive

19、protein and its implications in systemic lupus erythematosusJ. Acta reumatologica portuguesa, 2006, 32(4): 317-322.Marnell L, Mold C, Du Clos T W. C-reactive protein: ligands, receptors and role in inflammationJ. Clinical immunology, 2005, 117(2): 104-111.Rodriguez W, Mold C, Kataranovski M, Hutt J,

20、 Marnell LL and Du Clos TW. Reversal of ongoing proteinuria in autoimmune mice by treatment with C-reactive protein. Arthritis Rheum. 2005;52(2):642-650.Black S, Kushner I, Samols D. C-reactive proteinJ. Journal of Biological Chemistry, 2004, 279(47): 48487-48490.Sjowall C, Bengtsson AA, Sturfel G a

21、nd Skogh T. Serum levels of autoantibodies against monomeric C-reactive protein are correlated with disease activity in systemic lupus erythematosus. Arthritis Res Ther 2004; 6:R87-R94.Szalai AJ. C-reactive protein (CRP) and autoimmune disease: facts and conjectures. Clin Dev Immunol 2004;11:221-226

22、.Russell AI, Cunninghame Graham DS, Shepherd C, et al.Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus.Hum Mol Genet 2004;13:137-147.vLiou LB. Different Monocyte Reaction patterns in newly diagnosed, untreated rheumatoid arthriti

23、s and lupus patients probably confer disparate C-reactive protein levels.Clin Exp Rheumatol. 2003;21:437-444.Szalai AJ, Weaver CT, McCrory MA, et al. Delayed lupus onset in (Nzb X Nzw)F1 mice expressing a human C-reactive protein transgene. Arthritis Rheum. 2003;48:1602-1611.Mold C, Rodriguez W, Rodic-Polic B, et al. C-reactive protein mediates protection from lipopolysaccharide through interactions with FcRJ. The Journal of Immunology, 2002, 169(12): 7019-7025.Sjowall C, Eriksson P, Almer S and Skogh T. Autoantibodi