Liver injury correlates with biomarkers of autoimmunity and disease activity and represents an organ system involvement in patients with systemic lupus erythematosus

Clinical Immunology

Volumn 160, Issue 2, 2015, Pages 319-327

  Liu, Yuxin ^a   Yu, Jianghong ^a   Oaks, Zachary ^a   Marchena Mendez, Ivan ^a   Francis, Lisa ^a   Bonilla, Eduardo ^a   Aleksiejuk, Phillip ^a   Patel, Jessica ^a   Banki, Katalin ^b   Landas, Steve K ^b   Perl, Andras ^a  

^a STATE UNIVERSITY OF NEW YORK   (United States)

^b State University of New York Upstate Medical University: College of Medicine   (United States)

Author keywords

Autoimmunity; Disease activity; Liver disease; Lupus; Treatment

Indexed keywords

ACETYLCYSTEINE; ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; AZATHIOPRINE; BIOLOGICAL MARKER; CARDIOLIPIN; CYCLOPHOSPHAMIDE; CYCLOSPORIN A; DOUBLE STRANDED DNA ANTIBODY; HYDROXYCHLOROQUINE; LUPUS ANTICOAGULANT; MYCOPHENOLATE MOFETIL; PHOSPHOLIPID ANTIBODY; PREDNISONE; RAPAMYCIN; ANTINUCLEAR ANTIBODY; COMPLEMENT; CYCLOSPORIN; IMMUNOSUPPRESSIVE AGENT; MYCOPHENOLIC ACID; SCAVENGER;

ADULT; ANTIPHOSPHOLIPID SYNDROME; ARTICLE; AUTOIMMUNITY; CONTROLLED STUDY; DISEASE ACTIVITY; FEMALE; HUMAN; HUMAN TISSUE; HYPOCOMPLEMENTEMIA; IMMUNOSUPPRESSIVE TREATMENT; LETHAL DOSE; LEUKOPENIA; LIVER BIOPSY; LIVER INJURY; LONGITUDINAL STUDY; MAJOR CLINICAL STUDY; MALE; MASS; MYALGIA; OXIDATIVE STRESS; PATIENT; PREVALENCE; PRIORITY JOURNAL; PROTEINURIA; SLEDAI; SYSTEMIC LUPUS ERYTHEMATOSUS; THROMBOCYTOPENIA; TREATMENT RESPONSE; ANALOGS AND DERIVATIVES; BLOOD; COHORT ANALYSIS; DIABETES MELLITUS; IMMUNOLOGY; LIVER DISEASES; LUPUS ERYTHEMATOSUS, SYSTEMIC; MIDDLE AGED; RETROSPECTIVE STUDY; SEVERITY OF ILLNESS INDEX; SEX RATIO;

ACETYLCYSTEINE; ADULT; ALANINE TRANSAMINASE; ANTIBODIES, ANTINUCLEAR; ASPARTATE AMINOTRANSFERASES; AZATHIOPRINE; BIOMARKERS; COHORT STUDIES; COMPLEMENT SYSTEM PROTEINS; CYCLOSPORINE; DIABETES MELLITUS; FEMALE; FREE RADICAL SCAVENGERS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; LIVER DISEASES; LONGITUDINAL STUDIES; LUPUS ERYTHEMATOSUS, SYSTEMIC; MALE; MIDDLE AGED; MYCOPHENOLIC ACID; PREDNISONE; PREVALENCE; RETROSPECTIVE STUDIES; SEVERITY OF ILLNESS INDEX; SEX DISTRIBUTION; SIROLIMUS;

EID: 84938830004     PISSN: 15216616     EISSN: 15217035     Source Type: Journal    
DOI: 10.1016/j.clim.2015.07.001     Document Type: Article

References (74)

1. Perl A. Systems biology of lupus: mapping the impact of genomic and environmental factors on gene expression signatures, cellular signaling, metabolic pathways, hormonal and cytokine imbalance, and selecting targets for treatment. Autoimmunity 2010, 43:32-47.
2. Zheng R.H., Wang J.H., Wang S.B., Chen J., Guan W.M., Chen M.H. Clinical and immunopathological features of patients with lupus hepatitis. Chin. Med. J. 2013, 126:260-266.
3. Runyon B.A., LaBrecque D.R., Anuras S. The spectrum of liver disease in systemic lupus erythematosus. Report of 33 histologically-proved cases and review of the literature. Am. J. Med. 1980, 69:187-194.
4. Miller M.H., Urowitz M.B., Gladman D.D., Blendis L.M. The liver in systemic lupus erythematosus. Q. J. Med. 1984, 53:401-409.
5. Takahashi A., Abe K., Saito R., Iwadate H., Okai K., Katsushima F., Monoe K., Kanno Y., Saito H., Kobayashi H., Watanabe H., Ohira H. Liver dysfunction in patients with systemic lupus erythematosus. Intern. Med. 2013, 52:1461-1465.
6. Limdi J.K., Hyde G.M. Evaluation of abnormal liver function tests. Postgrad. Med. J. 2003, 79:307-312.
7. Nyblom H., Berggren U., Balldin J., Olsson R. High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy drinking. Alcohol Alcohol. 2004, 39:336-339.
8. Yang J.J., Huang C.H., Liu C.E., Tang H.J., Yang C.J., Lee Y.C., Lee K.Y., Tsai M.S., Lin S.W., Chen Y.H., Lu P.L., Hung C.C. Multicenter study of trimethoprim/sulfamethoxazole-related hepatotoxicity: incidence and associated factors among HIV-infected patients treated for Pneumocystis jirovecii pneumonia. PLoS One 2014, 9:e106141.
9. Mikl J., Sulkowski M.S., Benhamou Y., Dieterich D., Pol S., Rockstroh J., Robinson P.A., Ranga M., Stern J.O. Hepatic profile analyses of tipranavir in Phase II and III clinical trials. BMC Infect. Dis. 2009, 9:203.
10. Perl A. Mechanisms of viral pathogenesis in rheumatic diseases. Ann. Rheum. Dis. 1999, 58:454-461. (Invited Review).
11. Wu Y., You S., Zang H., Liu H., Mao Y., Mao P., Zhu B., Xu J., Xie G., Guo J., Li D., Xin S., Wan Z. Usefulness of serum thyroid-stimulation hormone (TSH) as a prognostic indicator for acute-on-chronic liver failure. Ann. Hepatol. 2015, 14:218-224.
12. Green J.R.B., Snitcher E.J., Mowat N.A.G., Ekins R.P., Rees L.H., Dawson A.M. Thyroid function and thyroid regulation in euthyroid men with chronic liver disease: evidence of multiple abnormalities. Clin. Endocrinol. 1977, 7:453-461.
13. Tan E.M., Cohen A.S., Fries J.F., Masi A.T., McShane D.J., Rothfield N.F., Schaller J.G., Talal N., Winchester R.J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982, 25:1271-1277.
14. Hochberg M.C. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997, 40:1725.
15. American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders 2013, American Psychiatric Publishing, Arlington, VA.
16. Ruhl C.E., Everhart J.E. Joint effects of body weight and alcohol on elevated serum alanine aminotransferase in the United States population. Clin. Gastroenterol. Hepatol. 2005, 3:1260-1268.
17. Bonilla E., Francis L., Allam F., Ogrinc M., Neupane H., Phillips P.E., Perl A. Immunofluorescence microscopy is superior to fluorescent beads for detection of antinuclear antibody reactivity in systemic lupus erythematosus patients. Clin. Immunol. 2007, 124:18-21.
18. Miyakis S., Lockshin M.D., Atsumi T., Branch D.W., Brey R.L., Cervera R., Derksen R.H., De Groot P.G., Koike T., Meroni P.L., Reber G., Shoenfeld Y., Tincani A., Vlachoyiannopoulos P.G., Krilis S.A. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J. Thromb. Haemost. 2006, 4:295-306. [see comment]. [136 refs].
19. Bombardier C., Gladman D.D., Urowitz M.B., Caron D., Chang C.H., the committee on prognosis studies in SLE Derivation of the SLEDAI. A disease activity index for lupus patients. Arthritis Rheum. 1992, 35:630-640.
20. Czaja A.J., Muratori P., Muratori L., Carpenter H.A., Bianchi F.B. Diagnostic and therapeutic implications of bile duct injury in autoimmune hepatitis. Liver Int. 2004, 24:322-329.
21. Gatselis N.K., Zachou K., Koukoulis G.K., Dalekos G.N. Autoimmune hepatitis, one disease with many faces: etiopathogenetic, clinico-laboratory and histological characteristics. World J. Gastroenterol. 2015, 21:60-83.
22. Abraham S., Begum S., Isenberg D. Hepatic manifestations of autoimmune rheumatic diseases. Ann. Rheum. Dis. 2004, 63:123-129. [see comment]. [Review].
23. Selmi C., De Santis M., Gershwin M.E. Liver involvement in subjects with rheumatic disease. Arthritis Res. Ther. 2011, 13:226.
24. Chowdhury V.R., Crowson C.S., Poterucha J.J., Moder K.G. Liver involvement in systemic lupus erythematosus: case review of 40 patients. J. Rheumatol. 2008, 35:2159-2164.
25. Piga M., Vacca A.F., Porru G.F., Cauli A.F., Mathieu A. Liver involvement in systemic lupus erythematosus: incidence, clinical course and outcome of lupus hepatitis. Clin. Exp. Rheumatol. 2010, 28:504-510.
26. Konikoff F., Isenberg D.A., Kooperman O., Kennedy R.C., Rauch J., Theodor E., Shoenfeld Y. Common lupus anti-DNA antibody idiotypes in chronic liver diseases. Clin. Immunol. Immunopathol. 1987, 43:265-272.
27. Sheth S.G., Flamm S.L., Gordon F.D., Chopra S. AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection. Am. J. Gastroenterol. 1998, 93:44-48.
28. Hanczko R., Fernandez D., Doherty E., Qian Y., Vas Gy., Niland B., Telarico T., Garba A., Banerjee S., Middleton F.A., Barrett D., Barcza M., Banki K., Landas S.K., Perl A. Prevention of hepatocarcinogenesis and acetaminophen-induced liver failure in transaldolase-deficient mice by N-acetylcysteine. J. Clin. Invest. 2009, 119:1546-1557.
29. Lai Z.-W., Borsuk R., Shadakshari A., Yu J., Dawood M., Garcia R., Francis L., Tily H., Bartos A., Faraone S.V., Phillips P.E., Perl A. mTOR activation triggers IL-4 production and necrotic death of double-negative T cells in patients with systemic lupus eryhthematosus. J. Immunol. 2013, 191:2236-2246.
30. Lai Z.-W., Marchena-Mendez I., Perl A. Oxidative stress and Treg depletion in lupus patients with anti-phospholipid syndrome. Clin. Immunol. 2015, 158:148-152.
31. Grammatikos A.P., Kyttaris V.C., Kis-Toth K., Fitzgerald L.M., Devlin A., Finnell M.D., Tsokos G.C. A T cell gene expression panel for the diagnosis and monitoring of disease activity in patients with systemic lupus erythematosus. Clin. Immunol. 2014, 150:192-200.
32. - double-negative lymphocytes in autoimmune MRL-lpr/lpr mice. J. Exp. Med. 1990, 172:7-12.
33. - Talpha/beta-cells in the liver is a common feature of autoimmune mice. J. Immunol. 1991, 147:2907-2912.
34. Fernandez D., Bonilla E., Mirza N., Niland B., Perl A. Rapamycin reduces disease activity and normalizes T-cell activation-induced calcium fluxing in patients with systemic lupus erythematosus. Arthritis Rheum. 2006, 54:2983-2988.
35. Lai Z.-W., Hanczko R., Bonilla E., Caza T.N., Clair B., Bartos A., Miklossy G., Jimah J., Doherty E., Tily H., Francis L., Garcia R., Dawood M., Yu J., Ramos I., Coman I., Faraone S.V., Phillips P.E., Perl A. N-acetylcysteine reduces disease activity by blocking mTOR in T cells of lupus patients. Arthritis Rheum. 2012, 64:2937-2946.
36. Perl A. Oxidative stress in the pathology and treatment of systemic lupus erythematosus. Nat. Rev. Rheumatol. 2013, 9:674-686.
37. Lunec J., Herbert K., Blount S., Griffiths H.R., Emery P. 8-Hydroxydeoxyguanosine. A marker of oxidative DNA damage in systemic lupus erythematosus. FEBS Lett. 1994, 348:131-138.
38. Pisetsky D.S. The origin and properties of extracellular DNA: from PAMP to DAMP. Clin. Immunol. 2012, 144:32-40.
39. Saxena N.K., Ikeda K., Rockey D.C., Friedman S.L., Anania F.A. Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice. Hepatology 2002, 35:762-771.
40. Amarilyo G., Iikuni N., Shi F.D., Liu A., Matarese G., La Cava A. Leptin promotes lupus T-cell autoimmunity. Clin. Immunol. 2013, 149:530-533.
41. Boteva L., Morris D., Cortes-Hernandez J., Martin J., Vyse T., Fernando M. Genetically determined partial complement C4 deficiency states are not independent risk factors for SLE in UK and Spanish populations. Am. J. Hum. Genet. 2012, 90:445-456.
42. Gibson T., Myers A.R. Subclinical liver disease in systemic lupus erythematosus. J. Rheumatol. 1981, 8:752-759.
43. Huang D., Aghdassi E., Su J., Mosko J., Hirschfield G.M., Gladman D.D., Urowitz M.B., Fortin P.R. Prevalence and risk factors for liver biochemical abnormalities in Canadian patients with systemic lupus erythematosus. J. Rheumatol. 2012, 39:254-261.
44. Gilmore I., Garvey C.J. Investigating and imaging the liver and biliary tract. Medicine 2007, 35:5-12.
45. Stein T.A., Burns G.P., Wise L. Diagnostic value of liver function tests in bile duct obstruction. J. Surg. Res. 1989, 46:226-229.
46. Oaks Z., Telarico T., Perl A. Mitochondrial dysfunction in the liver of lupus-prone MRL/Lpr mice prior to disease onset. Arthritis Rheum. 2012, 64(Suppl. 10):1455. (Ref Type: Abstract).
47. Bogdanos D.P., Gao B., Gershwin M.E. Liver immunology. Compr. Physiol. 2013, 3:567-598.
48. Fernandez D., Perl A. Metabolic control of T cell activation and death in SLE. Autoimmun. Rev. 2009, 8:184-189.
49. Chi H. Regulation and function of mTOR signalling in T cell fate decisions. Nat. Rev. Immunol. 2012, 12:325-338.
50. Perl A., Hanczko R., Lai Z.-W., Oaks Z., Kelly R., Borsuk R., Asara J.M., Phillips P.E. Comprehensive metabolome analyses reveal N-acetylcysteine-responsive accumulation of kynurenine in systemic lupus erythematosus: implications for activation of the mechanistic target of rapamycin. Metabolomics 2015, (in press, http://link.springer.com/article/10.1007/s11306-015-0772-0).
51. Hasko G., Linden J., Cronstein B., Pacher P. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat. Rev. Drug Discov. 2008, 7:759-770.
52. Mandler R., Birch R.E., Polmar S.H., Kammer G.M., Rudolph S.A. Abnormal adenosine-induced immunosuppression and cAMP metabolism in T lymphocytes of patients with systemic lupus erythematosus. Proc. Natl. Acad. Sci. U. S. A. 1982, 79:7542-7546.
53. Zhang L., Yang N., Wang S., Huang B., Li F., Tan H., Liang Y., Chen M., Li Y., Yu X. Adenosine 2A receptor is protective against renal injury in MRL/lpr mice. Lupus 2011, 20:667-677.
54. Balow J.E., Boumpas D.T., Austin H.A. New prospects for treatment of lupus nephritis. Semin. Nephrol. 2000, 20:32-39.
55. Young M.C., Bangs J.D., Borel Y. Immune suppression to nucleosides: differences between NZB and NZW mice. Eur. J. Immunol. 1981, 11:424-428.
56. Lautt W.W. Regulatory processes interacting to maintain hepatic blood flow constancy: vascular compliance, hepatic arterial buffer response, hepatorenal reflex, liver regeneration, escape from vasoconstriction. Hepatol. Res 2007, 37:891-903.
57. Yamagiwa S., Kamimura H., Takamura M., Aoyagi Y. Autoantibodies in primary biliary cirrhosis: recent progress in research on the pathogenetic and clinical significance. World J. Gastroenterol. 2014, 20:2606-2612.
58. Arnett F.C., Reichlin M. Lupus hepatitis: an under-recognized disease feature associated with autoantibodies to ribosomal P. Am. J. Med. 1995, 99:465-472.
59. Bessone F., Poles N., Roma M.G. Challenge of liver disease in systemic lupus erythematosus: clues for diagnosis and hints for pathogenesis. World J. Hepatol. 2014, 6:394-409.
60. Zhang W.C. Meta-analysis: diagnostic accuracy of antinuclear antibodies, smooth muscle antibodies and antibodies to a soluble liver antigen/liver pancreas in autoimmune hepatitis. PLoS One 2014, 9:e92267.
61. Kurowski J., Melin-Aldana H., Bass L., Alonso E.M., Ekong U.D. Sirolimus as rescue therapy in pediatric autoimmune hepatitis. J. Pediatr. Gastroenterol. Nutr. 2014, 58:e4-e6.
62. Selvarajah V., Montano-Loza A.J., Czaja A.J. Systematic review: managing suboptimal treatment responses in autoimmune hepatitis with conventional and nonstandard drugs. Aliment. Pharmacol. Ther. 2012, 36:691-707.
63. Larsen F.S. Treatment of patients with severe autoimmune hepatitis. Minerva Gastroenterol. Dietol. 2008, 54:57-63.
64. Larson A.M., Polson J., Fontana R.J., Davern T.J., Lalani E., Hynan L.S., Reisch J.S., Schiodt F.V., Ostapowicz G., Shakil A.O., Lee W.M., Acute Liver Failure Study Group Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology 2005, 42:1364-1372. [see comment].
65. Singh S., Hynan L.S., Lee W.M. Improvements in hepatic serological biomarkers are associated with clinical benefit of intravenous N-acetylcysteine in early stage non-acetaminophen acute liver failure. Dig. Dis. Sci. 2013, 58:1397-1402.
66. Lee W.M., Hynan L.S., Rossaro L., Fontana R.J., Stravitz R.T., Larson A.M., Vern T.J., Murray N.G., McCashland T., Reisch J.S., Robuck P.R. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology 2009, 137:856-864.
67. Francis L., Perl A. Pharmacotherapy of systemic lupus erythematosus. Expert Opin. Pharmacother. 2009, 10:1481-1494.
68. Bernatsky S., Ramsey-Goldman R., Labrecque J., Joseph L., Boivin J.F., Petri M., Zoma A., Manzi S., Urowitz M., Gladman D., Fortin P.R., Ginzler E., Yelin E., Bae S.C., Wallace D.J., Edworthy S., Jacobsen S., Gordon C., Dooley M.A., Peschken C.A., Hanly J.G., Alarcon G.S., Nived O., Ruiz-Irastorza G., Isenberg D., Rahman A., Witte T., Aranow C., Kamen D.L., Steinsson K., Askanase A., Barr S., Criswell L.A., Sturfelt G., Patel N.M., Senecal J.L., Zummer M., Pope J.E., Ensworth S., El-Gabalawy H., McCarthy T., Dreyer L., Sibley J., Pierre Y., Clarke A.E. Cancer risk in systemic lupus: an updated international multi-centre cohort study. J. Autoimmun. 2013, 42:130-135.
69. Bernatsky S., Boivin J.F., Joseph L., Rajan R., Zoma A., Manzi S., Ginzler E., Urowitz M., Gladman D., Fortin P.R., Petri M., Edworthy S., Barr S., Gordon C., Bae S.C., Sibley J., Isenberg D., Rahman A., Aranow C., Dooley M.A., Steinsson K., Nived O., Sturfelt G., Alarcon G., Senecal J.L., Zummer M., Hanly J., Ensworth S., Pope J., El Gabalawy H., McCarthy T., St Pierre Y., Ramsey-Goldman R., Clarke A. An international cohort study of cancer in systemic lupus erythematosus. Arthritis Rheum. 2005, 52:1481-1490.
70. Perl A., Hanczko R., Telarico T., Oaks Z., Landas S. Oxidative stress, inflammation and carcinogenesis are controlled through the pentose phosphate pathway by transaldolase. Trends Mol. Med. 2011, 7:395-403.
71. Gergely P.J., Grossman C., Niland B., Puskas F., Neupane H., Allam F., Banki K., Phillips P.E., Perl A. Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus. Arthritis Rheum. 2002, 46:175-190.
72. Fujii J., Kurahashi T., Konno T., Homma T., Iuchi Y. Oxidative stress as a potential causal factor for autoimmune hemolytic anemia and systemic lupus erythematosus. World J. Nephrol. 2015, 4:213-222.
73. Asherson R.A., Cervera R., Piette J.C., Font J., Lie J.T., Burcoglu A., Lim K., Munoz-Rodriguez F.J., Levy R.A., Boue F., Rossert J., Ingelmo M. Catastrophic antiphospholipid syndrome: clinical and laboratory features of 50 patients. Medicine 1998, 77:195-207.
74. Ambrosino P., Lupoli R., Spadarella G., Tarantino P., Di Minno A., Tarantino L., Di Minno M.N.D. Autoimmune liver diseases and antiphospholipid antibodies positivity: a meta-analysis of literature studies 2015, 24:25-34.