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Bilirubin levels in patients with systemic lupus erythematosus: increased or decreased?

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Abstract

The aim of this study was to investigate the serum bilirubin levels in SLE patients and their associations with clinical and laboratory characteristics of SLE. There were 198 SLE patients in this study, of whom 7 cases with tobacco smoking or alcohol intake were excluded. Some clinical and laboratory characteristics of the patients were obtained by medical record review. In addition, 154 age- and sex- matched healthy volunteers with no histories of SLE, liver diseases, and other autoimmune or inflammatory diseases were randomly recruited into this study. The serum bilirubin levels were lower in SLE patients without liver diseases than in healthy controls (P = 0.000). Univariate logistic analysis demonstrated that hypertension, lupus renal involvement, positive anti-dsDNA antibody, C3, C4, hsCRP, and albumin remained as impact factors of total bilirubins; lupus renal involvement, ESR, IgG, globulin, and ALT, as impact factors of direct bilirubins; and lupus renal involvement, positive anti-dsDNA antibody, C3, C4, hsCRP, and albumin, as impact factors of indirect bilirubins. However, multivariate logistic analysis showed that only hsCRP remained as an independent positive impact factor of total bilirubins, lupus renal involvement as an independent negative impact factor of direct bilirubins, and hsCRP and albumin as independent positive impact factors of indirect bilirubins. In conclusion, serum bilirubin levels are decreased in SLE and the decreased bilirubin levels could be associated with inflammatory process and lupus renal involvement of SLE.

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References

  1. Morgan PE, Sturgess AD, Davies MJ (2009) Evidence for chronically elevated serum protein oxidation in systemic lupus erythematosus patients. Free Radic Res 43:117–127

    Article  PubMed  CAS  Google Scholar 

  2. Wang G, Pierangeli SS, Papalardo E, Ansari GAS, Khan MF (2010) Markers of oxidative and nitrosative stress in systemic lupus erythematosus: correlation with disease activity. Arthritis Rheum 62:2064–2072

    PubMed  CAS  Google Scholar 

  3. Grimsrud PA, Xie H, Griffin TJ, Bernlohr DA (2008) Oxidative stress and covalent modification of protein with bioactive aldehydes. J Biol Chem 283:21837–21841

    Article  PubMed  CAS  Google Scholar 

  4. Ozkan Y, Yardym-Akaydyn S, Sepici A, Keskin E, Sepici V, Simsek B (2007) Oxidative status in rheumatoid arthritis. Clin Rheumatol 26:64–68

    Article  PubMed  Google Scholar 

  5. Shacter E (2000) Quantification and significance of protein oxidation in biological samples. Drug Metab Rev 32:307–326

    Article  PubMed  CAS  Google Scholar 

  6. Grimsrud PA, Xie H, Griffin TJ, Bernlohr DA (2008) Oxidative stress and covalent modification of protein with bioactive aldehydes. J Biol Chem 283:21837–21841

    Article  PubMed  CAS  Google Scholar 

  7. Wang WW, Smith DL, Zucker SD (2004) Bilirubin inhibits iNOS expression and NO production in response to endotoxin in rats. Hepatology 40:424–433

    Article  PubMed  CAS  Google Scholar 

  8. Wang H, Lee SS, Dell’ Agnello C, Tchipashvili V, d’Avila JC, Czismadia E, Chin BY, Bach FH (2006) Bilirubin can induce tolerance to islet allografts. Endocrinology 147:762–768

    Article  PubMed  CAS  Google Scholar 

  9. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–1046

    Article  PubMed  CAS  Google Scholar 

  10. Wu TW, Carey D, Wu J, Sugiyama H (1991) The cytoprotective effects of bilirubin and biliverdin on rat hepatocytes and human erythrocytes and the impact of albumin. Biochem Cell Biol 69:824–828

    Google Scholar 

  11. Erdogan D, Gullu H, Yildirim E et al (2006) Low serum bilirubin levels are independently and inversely related to impaired flow-mediated vasodilation and increased carotid intima-media thickness in both men and women. Atherosclerosis 184:431–437

    Article  PubMed  CAS  Google Scholar 

  12. Perlstein TS, Pande RL, Beckman JA, Creager MA (2008) Serum total bilirubin level and prevalent lower-extremity peripheral arterial disease: national health and nutrition examination survey (NHANES) 1999–2004. Arterioscler Thromb Vasc Biol 28:166–172

    Article  PubMed  CAS  Google Scholar 

  13. Vitek L, Novotny L, Sperl M, Holaj R, Spacil J (2006) The inverse association of elevated serum bilirubin levels with subclinical carotid atherosclerosis. Cerebrovasc Dis 21:408–414

    Article  PubMed  CAS  Google Scholar 

  14. Tanaka M, Fukui M, Tomiyasu K, Akabame S, Nakano K, Hasegawa G, Oda Y, Nakamura N (2009) Low serum bilirubin concentration is associated with coronary artery calcification (CAC). Atherosclerosis 206:287–291

    Article  PubMed  CAS  Google Scholar 

  15. Idriss NK, Blann AD, Lip GYH (2008) Hemoxygenase-1 in cardiovascular disease. J Am Coll Cardiol 52(12):971–978

    Article  PubMed  CAS  Google Scholar 

  16. Liu Y, Zhu B, Wang X, Luo L, Li P, Paty DW, Cynader MS (2003) Bilirubin as a potent antioxidant suppresses experimental autoimmune encephalomyelitis: implications for the role of oxidative stress in the development of multiple sclerosis. J Neuroimmunol 139:27–35

    Article  PubMed  CAS  Google Scholar 

  17. Hochberg MC (1997) Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthritis Rheum 40:1725

    Article  PubMed  CAS  Google Scholar 

  18. Renal disease subcommittee of the American college of rheumatology ad hoc committee on systemic lupus erythematosus response criteria (2006) The American college of rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials. Arthritis Rheum 54:421–432

    Google Scholar 

  19. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang DH, The Committee on Prognosis Studies in SLE (1992) Derivation of the SLEDAI: a disease activity index for lupus patients. Arthritis Rheum 35:630–640

    Article  PubMed  CAS  Google Scholar 

  20. Giral P, Ratziu V, Couvert P, Carrie A, Kontush A, Girerd X, Chapman MJ (2010) Plasma bilirubin and gamma-glutamyltransferase activity are inversely related in dyslipidemic patients with metabolic syndrome: relevance to oxidative stress. Atherosclerosis 210:607–613

    Article  PubMed  CAS  Google Scholar 

  21. Vítek L, Muchová L, Jančová E, Pešičková S, Tegzová D, Peterová V, Pavelka K, Tesař V (2010) Association of systemic lupus erythematosus with low serum bilirubin levels. Scand J Rheumatol 39:480–484

    Article  PubMed  Google Scholar 

  22. Bound S, Griffiths HR, Emery P, Lunec J (1991) Reactive oxygen species damage to DNA and its role in systemic lupus erythematosus. Mol Aspects Med 12:93–105

    Article  Google Scholar 

  23. Cooke MS, Evans MD, Herbert KE, Lunec J (1997) Immunogenicity of DNA damaged by reactive oxygen species-implication for anti-DNA antibodies in lupus. Free Radic Biol Med 22:151–159

    Article  PubMed  CAS  Google Scholar 

  24. Comstock GW, Burke AE, Hoffman SC, Helzlsouer KJ, Bendich A, Masi AT et al (1997) Serum concentrations of α-tocopherol, β-carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis 56:323–325

    Article  PubMed  CAS  Google Scholar 

  25. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–1046

    Article  PubMed  CAS  Google Scholar 

  26. Wu TW, Fung KP, Wu J, Yang CC, Weisel RD (1996) Antioxidation of human low density lipoprotein by unconjugated and conjugated bilirubins. Biochem Pharmacol 51:859–862

    Article  PubMed  CAS  Google Scholar 

  27. Tomaro ML, Batlle AM (2002) Bilirubin: its role in cytoprotection against oxidative stress. Int J Biochem Cell Biol 34:216–220

    Article  PubMed  CAS  Google Scholar 

  28. Oakes GH, Bend JR (2005) Early steps in bilirubin-mediated apoptosis in murine hepatoma (Hepa 1c1c7) cells are characterized by aryl hydrocarbon receptor-independent oxidative stress and activation of the mitochondrial pathway. J Biochem Mol Toxicol 19:244–255

    Article  PubMed  CAS  Google Scholar 

  29. Ostrow JD, Pascolo L, Tiribelli C (2003) Reassessment of the unbound concentrations of unconjugated bilirubin in relation to neurotoxicity in vitro. Pediatr Res 54:98–104

    Article  PubMed  CAS  Google Scholar 

  30. Korbet SM, Jewis EJ, Schwartz MM, Reichlin M, Evans J, Rohde RD, The Lupus Nephritis Collaborative Study Group (2000) Factors predictive of outcome in severe lupus nephritis. Am J Kidney Dis 35:904–914

    Article  PubMed  CAS  Google Scholar 

  31. Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. N Engl J Med 358:929–939

    Article  PubMed  CAS  Google Scholar 

  32. Arriaga SM, Mottino AD, Almara AM (1999) Inhibitory effect of bilirubin on complement-mediated hemolysis. Biochem Biophys Acta 1473:329–336

    Article  PubMed  CAS  Google Scholar 

  33. Basiglio CL, Arriaga SM, Pelusa HF, Almara AM, Roma MG, Mottino AD (2007) Protective role of unconjugated bilirubin on complement-mediated hepatocytolysis. Biochem Biophys Acta 1770:1003–1010

    Article  PubMed  CAS  Google Scholar 

  34. Kinderlerer AR, Gregoire IP, Hamdulay SS, Ali F, Steinberg R, Silva G, Ali N, Wang B, Haskard DO, Soares MP, Mason JC (2009) Heme oxygenase-1 expression enhances vascular endothelial resistance to complement-mediated injury through induction of decay-accelerating factor: a role of increased bilirubin and ferritin. Blood 113:1598–1607

    Article  PubMed  CAS  Google Scholar 

  35. Elias MM, Comin EJ, Garay EA (1977) Renal clearance of unbound bilirubin in the rat. Clin Sci Mol Med 53:193–196

    PubMed  CAS  Google Scholar 

  36. Don BR, Kaysen G (2004) Serum albumin: relationship to inflammation and nutrition. Semin Dial 17:432–437

    Article  PubMed  Google Scholar 

  37. Djousse L, Rothman KJ, Cupples LA, Levy D, Ellison RC (2002) Serum albumin and risk of myocardial infarction and all-cause mortality in the Framingham offspring study. Circulation 106:2919–2924

    Article  PubMed  CAS  Google Scholar 

  38. Ohnaka K, Kono S, Inoguchi T, Yin G, Morita M, Adachi M, Kawate H, Takayanagi R (2010) Inverse associations of serum bilirubin with high sensitivity C-reactive protein, glycated hemoglobin, and prevalence of type 2 diabetes in middle-aged and elderly Japanese men and women. Diabetes Res Clin Pract 88:103–110

    Article  PubMed  CAS  Google Scholar 

  39. Gullu H, Erdogan D, Tok D, Topcu S, Caliskan M, Ulus T, Muderrisoglu H (2005) High serum bilirubin concentrations preserve coronary flow reserve and coronary microvascular functions. Arterioscler Thromb Vasc Biol 25:2289–2294

    Article  PubMed  CAS  Google Scholar 

  40. Lin LY, Kuo HK, Hwang JJ, Lai LP, Chiang FT, Tseng CD, Lin JL (2009) Serum bilirubin is inversely associated with insulin resistance and metabolic syndrome among children and adolescents. Atherosclerosis 203:563–568

    Article  PubMed  CAS  Google Scholar 

  41. Marnell L, Mold C, Du Clos TW (2005) C-reactive protein: ligands, receptors and role in inflammation. Clin Immunol 117:104–111

    Article  PubMed  CAS  Google Scholar 

  42. Gershov D, Kim S, Brot N, Elkon KB (2000) C-reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity. J Exp Med 192:1353–1364

    Article  PubMed  CAS  Google Scholar 

  43. Becker GJ, Waldburger M, Hughes GR, Pepys MB (1980) Value of serum C-reactive protein measurement in the investigation of fever in systemic lupus erythematosus. Ann Rheum Dis 39:50–52

    Article  PubMed  CAS  Google Scholar 

  44. Russell AI, Cunninghame Graham DS, Shepherd C, Roberton CA, Whittaker J, Meeks J et al (2004) Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus. Hum Mol Genet 13:137–147

    Article  PubMed  CAS  Google Scholar 

  45. Rodriguez W, Mold C, Marnell LL, Hutt J, Silverman GJ, Tran D et al (2006) Prevention and reversal of nephritis in MRL/lpr mice with a single injection of C-reactive protein. Arthritis Rheum 54:325–335

    Article  PubMed  CAS  Google Scholar 

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No conflict of interest has been declared by the authors.

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Authors and Affiliations

  1. Department of Laboratory Diagnostics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, China

    Zaixing Yang, Yan Liang, Chang Li & Renqian Zhong

  2. Department of Information Center, Changzheng Hospital, Second Military Medical University, Shanghai, China

    Weiqiang Xi

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  1. Zaixing Yang
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  2. Yan Liang
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  3. Chang Li
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  4. Weiqiang Xi
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  5. Renqian Zhong
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Correspondence to Renqian Zhong.

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Z. Yang and Y. Liang contributed equally to this work.

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Yang, Z., Liang, Y., Li, C. et al. Bilirubin levels in patients with systemic lupus erythematosus: increased or decreased?. Rheumatol Int 32, 2423–2430 (2012). https://doi.org/10.1007/s00296-011-1977-9

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  • DOI: https://doi.org/10.1007/s00296-011-1977-9

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