Skip to main content
SpringerLink
Log in

Immune Phenotype of Chronic Liver Disease

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Immune disorders in chronic liver disease mayreflect common host propensities or diseasespecificfactors. Our aim was to determine the principal basesfor these expressions. Four hundred fifty-one patients with various chronic liver diseases wereassessed prospectively for concurrent immune disorders.Individuals with immune diseases were more frequentlywomen (73% vs 60%, P = 0.02) and they had HLA DR4 more often than counterparts with other HLA(46% vs 23%, P = 0.000008). The association between HLADR4 and immune disease was apparent within individualliver diseases and within different categories of liver disease. Women with HLA DR4 had ahigher frequency of immune disease than women withoutHLA DR4 (52% vs 22%, P ≤ 0.000001), and they also hadimmune diseases more commonly than DR4-positive men (52% vs 31%, P = 0.03). DR4-positive men,however, had higher frequencies of immune disease thanDR4-negative men, especially in the nonimmune types ofliver disease (26% vs 4%, P = 0.002). We conclude that HLA DR4 and female gender constitute animmune phenotype that is an important basis forautoimmune expression in chronic liverdisease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB, Taswell HF, Homburger HA: Evidence against hepatitis viruse s as important causes of severe autoimmune hepatitis in the United States. J Hepatol 18:342 - 352, 1993

    PubMed  Google Scholar 

  2. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB: Genetic predispositions for the immunological features of chronic active hepatitis. Hepatology 18:816 - 822, 1993

    PubMed  Google Scholar 

  3. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB: Significance of HLA DR4 in type 1 autoimmune hepatitis. Gastroenterology 105:1502 - 1507, 1993

    PubMed  Google Scholar 

  4. Czaja AJ, Strettell MDJ, Thomson LJ, Santrach PJ, Moore SB, Donaldson PT, Williams R: Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis. Hepatology 25:317 - 323, 1997

    PubMed  Google Scholar 

  5. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB: Immunologic features and HLA associations in chronic viral hepatitis. Gastroenterology 108:157 - 164, 1995

    PubMed  Google Scholar 

  6. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB: Significance of human leukocyte antigens DR3 AND DR4 in chronic viral hepatitis. Dig Dis Sci 40:2098 - 2106, 1995

    PubMed  Google Scholar 

  7. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB: Genetic predispositions for immunological features in chronic liver diseases other than autoimmune hepatitis. J Hepatol 24:52–59, 1996

    Google Scholar 

  8. Czaja AJ: Extrahepatic immunologic features of chronic viral hepatitis. Dig Dis 15:125 - 144, 1997

    PubMed  Google Scholar 

  9. Griffing WL, Moore SB, Luthra HS, McKenna CH, Fathman CG: Associations of antibodies to native DNA with HLADRw3: A possible major histocompatibility complex-linked human immune response gene. J Exp Med 152:319s - 325s, 1980

    PubMed  Google Scholar 

  10. Fujinami RS, Oldstone MBA, Wroblewska Z, Frankel ME, Koprowski H: Molecular mimicry in virus infection: Crossreaction of measle s virus phosphoprotein or of herpes simplex virus protein with human intermediate fi laments. Proc Natl Acad Sci USA 80:2346 - 2350, 1983

    PubMed  Google Scholar 

  11. Peters M: Actions of cytokines on the immune response and viral interactions: an overview. Hepatology 23:909 - 916, 1996

    Article  PubMed  Google Scholar 

  12. O'Brien CJ, Vento S, Donaldson PT, McSorley CG, McFarlane IG, Williams R, Eddleston ALWF: Cell-mediated immunity and suppressor-T-cell defects to liver-derived antigens in families of patients with autoimmune chronic active hepatitis. Lancet 1:350 - 353, 1986

    Article  PubMed  Google Scholar 

  13. Strettell MDJ, Donaldson PT, Thomson LJ, Santrach PJ, Moore SB, Czaja AJ, Williams R: Allelic basis for HLAencoded susceptibility to type 1 autoimmune hepatitis. Gastroenterology 112:2028 - 2035, 1997

    PubMed  Google Scholar 

  14. Johnson PJ, McFarlane IG, Alvarez F, Bianchi FB, Bianchi L, Burroughs A, Chapman RW, Czaja AJ, De smet V, Edleston ALWF, Gerber MA, Hoofnagle JH, Kakumu S, MacSween RNM, Maddre y WC, Manns MP, Meyerzum Buschenfelde K-H, Mieli-Vergani G, Portmann BC, Reed WD, Schalm SW, Scheuer PJ, Toda G, Tsuji T, Tygstrup N, Ve rgani D, Zeniya M: Meeting report. International Autoimmune Hepatitis Group. Hepatology 18:998 - 1005, 1993

    PubMed  Google Scholar 

  15. Czaja AJ, Manns MP: The validity and importance of subtypes of autoimmune hepatitis: A point of view. Am J Gastroenterol 90:1206 - 1211, 1995

    PubMed  Google Scholar 

  16. Hay ID: Thyroiditis: A clinical update. Mayo Clin Proc 60:836 - 843, 1985

    PubMed  Google Scholar 

  17. De Bruin TWA, Bolk JH, Bussemaker JK, Stijnen T, Schre-uder GMT, De Vries RRP, Van Der Heide D: Graves' disease: Immunological and immunogene tic indicators of relapse. Br Med J 296:1292 - 1295, 1988

    Google Scholar 

  18. Homberg J-C, Abuaf N, Bernard O, Islam S, Alvarez F, Khalil SH, Poupon R, Darnis F, Levy V-G, Grippon P, Opolon P, Bernuau J, Benhamou J-P, Alagille D: Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: A second type of “autoimmune” hepatitis. Hepatology 7:1333 - 1339, 1987

    PubMed  Google Scholar 

  19. Czaja AJ, Nishioka M, Morshed SA, Hachiya T: Patterns of nuclear immunofluorescence and reactivities to recombinant nuclear antigens in autoimmune hepatitis. Gastroenterology 107:200 - 207, 1994

    PubMed  Google Scholar 

  20. Czaja AJ, Cassani F, Catale ta M, Valentini P, Bianchi FB: Frequency and significance of antibodies to actin in type 1 autoimmune hepatitis. Hepatology 24:1068 - 1073, 1996

    Article  PubMed  Google Scholar 

  21. Czaja AJ, Manns MP, Homburger HA: Frequency and significance of antibodies to liver/kidneymicrosome type 1 in adults with chronic active hepatitis. Gastroenterology 103:1290 - 1295, 1992

    PubMed  Google Scholar 

  22. Czaja AJ, Carpenter HA, Manns MP: Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexe s in chronic hepatitis. Gastroenterology 105:1522- 1528, 1993

    PubMed  Google Scholar 

  23. Fulthorpe AJ, Roitt IM, Doniach D, Couchman K: A stable sheep cell preparation for detecting thyroglobulin antibodies and its clinical application. J Clin Pathol 14:654 - 660, 1961

    PubMed  Google Scholar 

  24. Doniach D: Thyroid autoimmune disease. J Clin Pathol 20:385 - 390, 1967

    Google Scholar 

  25. Bird T, Stephenson J: Evaluation of a tanned red cell technique for thyroid microsomal antibodies. J Clin Pathol 26:623 - 627, 1973

    PubMed  Google Scholar 

  26. Bidwell JL, Bidwell EA, Savage DA, Middleton D, Klouda PT, Bradley BA: A DNA-RFLP typing system that positively identi fies serologically well-defined and ill-defined HLA-DR and DQ alleles, including Drw10. Transplantation 45:640 - 646, 1988

    PubMed  Google Scholar 

  27. Olerup O, Ze tterquist H: HLA-DR typing by PCR amplifi cation with sequence-specific primers (PCR-SSP) in 2 hours: An alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation. Tissue Antigens 39:225 - 235, 1992

    PubMed  Google Scholar 

  28. Beeson PB: Age and sex associations of 40 autoimmune disorders. Am J Med 96:457 - 462, 1994

    PubMed  Google Scholar 

  29. Lahita RG: The connective tissue disease s and the overall influence of gender. Int J Fertil 41:156 - 165, 1996

    Google Scholar 

  30. Rowley MJ, Mackay IR: Measurement of antibody-producing capacity in man. I. the normal response to flagellan from Salmonella adelaide.Clin Exp Immunol 5:407- 418, 1969

    PubMed  Google Scholar 

  31. Eidinger D, Garret TJ: Studies of the regulatory effects of the sex hormones on antibody formation and stem cell differentiation. J Exp Med 136:1098 - 1116, 1972

    PubMed  Google Scholar 

  32. Mackay IR, Whittingham S, Tait B: Genetic control of immune responsiveness in man. Vox Sang 32:10 - 19, 1977

    PubMed  Google Scholar 

  33. Hooper B, Whittingham S, Mathews JD, Mackay IR, Curnow DH: Autoimmunity in a rural community. Clin Exp Immunol 12:79 - 87, 1972

    PubMed  Google Scholar 

  34. Czaja AJ: Autoantibodies. Bailliere's Clin Gastroenterol 9:723 - 744, 1995

    Google Scholar 

  35. Wilder RL: Hormones and autoimmunity: Animal models of arthritis. Bailliere' s Clin Rheumatol 10:259 - 271, 1996

    Google Scholar 

  36. Chao TC, Van Alten PJ, Greager JA, Walter RJ: Steroid sex hormones regulate the re lease of tumor necrosis factor by macrophages. Cell Immun 160:43 - 49, 1995

    Google Scholar 

  37. Paavonen T, Andersson LC, Adlercreutz H: Sex hormone regulation of in vitroimmune response. Estradiol enhances human B cell maturation via inhibition of suppressor T cells in pokeweed mitogen-stimulated cultures. J Exp Med 154:1935 - 1945, 1981

    PubMed  Google Scholar 

  38. Muller D, Chen M, Vikingsson A, Hildeman D, Pederson K: Oestrogen influence s CD4+ T-lymphocyte activity in vivoand in vitroin β2-microglobulin-deficient mice. Immunology 86:162 - 167, 1995

    PubMed  Google Scholar 

  39. Cannon JG, St. Pierre BA: Gender differences in host defense me chanisms. J Psychol Res 31:99 - 113, 1997

    Google Scholar 

  40. Fox HS, Bond BL, Parslow TG: Oestrogen regulates the IFN-γ promoter. J Immunol 146:4362- 4367, 1991

    PubMed  Google Scholar 

  41. Blomberg G, Geckeler WR, Weigert M: Genetics of the antibody response to dextran in mice. Science 177:178 - 180, 1972

    PubMed  Google Scholar 

  42. Talal N, Roubinian JR: Sex hormone s and autoimmunity. InGenetic Control of Autoimmune Disease. NR Rose, PE Bigazzi, NL Warner (eds). New York, Elsevier-North Holland, 1978, pp 163- 174

    Google Scholar 

  43. Paavonen T: Hormonal regulation of immune responses. Ann Med 26:255- 258, 1994

    PubMed  Google Scholar 

  44. Reber PM: Prolactin and immunoregulation. Am J Med 95:637- 644, 1993

    PubMed  Google Scholar 

  45. Van Griensven M, Bergijk EC, Baelde JJ, De Heer E, Bruijn JA: Differential effects of sex hormone s on autoantibody production and proteinuria in chronic graft-versus-host disease-induced experimental lupus nephritis. Clin Exp Immunol 107:254 - 260, 1997

    PubMed  Google Scholar 

  46. Kaufman JF, Auffray C, Korman AJ, Shacke lford DA, Strominger J: The class II molecule s of the human and murine major histocompatibility complex. Cell 36:1- 13, 1984

    PubMed  Google Scholar 

  47. Brown JH, Jardetzky T, Saper MA, Samraoui B, Bjorkman PJ, Wiley DC: A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature 332:845- 850, 1988

    PubMed  Google Scholar 

  48. Manns MP, Griffi n KJ, Sullivan KF, Johnson EF: LKM-1 autoantibodie s recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase. J Clin Invest 88:1370 - 1378, 1991

    PubMed  Google Scholar 

  49. Payami H, Khan MA, Grennan DM, Sanders PA, Dyer PA, Thomson G: Analysis of gene tic interre lationship among HLAassociated diseases. Am J Hum Genet 41:331- 349, 1987

    PubMed  Google Scholar 

  50. Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Pe rrin M, Grippon P, Hoang C, Piette JC, Huraux J-M, Opolon P: Cryoglobulinemia in chronic liver diseases: Role of hepatitis C virus and liver damage. Gastroente rology 106:1291- 1300, 1994

    Google Scholar 

  51. Pawlotsky J-M, Roudot-Thoraval F, Simmonds P, Mellor J, Ben Yahia M, Andre C, Voisin M-C, Intrator L, Zafrani E-S, Duval J, Dhumeaux D: Extrahe patic immunologic manifestations in chronic hepatitis C and hepatitis C serotypes. Ann Intern Med 122:169 - 173, 1995

    PubMed  Google Scholar 

Download references

Authors
  1. Albert J. Czaja
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rui Marques
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dos Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Armando Porto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paula J. Santrach
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Breanndan Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Czaja, A.J., Marques, R., Santos, D. et al. Immune Phenotype of Chronic Liver Disease. Dig Dis Sci 43, 2149–2155 (1998). https://doi.org/10.1023/A:1018836004279

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018836004279

Search

Navigation