IMMUNE RESPONSES IN AUTOIMMUNE HEPATITIS: EFFECT OF PREDNISONE AND AZATHIOPRINE TREATMENT: CASE REPORT

The role of the immune response in autoimmune hepatitis has not been studied before and after prednisone and azathioprine treatment. Distributions of blood lymphocytes (CD4+, CD8+, CD19+, CD23+, CD16/56+), levels of serum immunoglobulins (IgM, IgG, IgE, IgA) and cytokines (IFN-γ, IL-4, IL-12, TNFα ) were studied in a child (f/14 y/o) with autoimmune hepatitis before and after prednisone (20 mg/d) and azathioprine (50 mg/d) treatment (nephelometry, UniCAP Total IgE Fluoroenzymeimmunoassay, flow cytometry, cytokine ELISA). Patient was studied for 0-2.5 yrs; treatment was initiated 12 weeks post diagnosis. Numbers of CD4+ T cells increased (50%), while CD19+ and CD23+ cells decreased (>50%) post treatment; other lymphocyte subsets were unaffected by treatment. Serum IgG and IgE levels decreased (>50%) after treatment; serum IgM and IgA were within normal range and were not affected by treatment High levels of IFN-γ (5-23 pg/ml) were initially detected in serum, which decreased after treatment (<0.1 pg/ml). Furthermore, low levels of IL-4 (0.2 pg/mL) were detected before treatment, which were not detected after treatment (<0.1 pg/ml). In contrast, before treatment, IL-12 and TNFα were not detected in serum; however after treatment the levels of IL-12 and TNFα dramatically increased. Prednisone and azathioprine treatment decreased total serum IgG, IgE, IFN-γ and IL-4 levels, and blood CD19+ and CD23+ cells; however serum IL-12, TNFα and blood CD4+ T cells increased with treatment. Understanding immunomodulation in autoimmune hepatitis will provide better insight and mechanisms of this disease and may tailor more effective therapeutic intervention.

[1]  D. Vergani,et al.  Aetiopathogenesis of autoimmune hepatitis. , 2010, Journal of autoimmunity.

[2]  S. Cullen,et al.  Management of autoimmune liver disease. , 2009, Minerva gastroenterologica e dietologica.

[3]  G. Maggiore,et al.  Autoimmune diseases of the liver and biliary tract and overlap syndromes in childhood. , 2009, Minerva gastroenterologica e dietologica.

[4]  G. Gerken,et al.  Phenotypical analysis and cytokine release of liver-infiltrating and peripheral blood T lymphocytes from patients with chronic hepatitis of different etiology. , 2008, Liver.

[5]  G. Ahlenstiel,et al.  Identification of CD4 T-cell epitopes in soluble liver antigen/liver pancreas autoantigen in autoimmune hepatitis. , 2008, Gastroenterology.

[6]  P. Allen,et al.  Hepatitis resulting from liver-specific expression and recognition of self-antigen. , 2008, Journal of autoimmunity.

[7]  D. Vergani,et al.  Autoimmune paediatric liver disease. , 2008, World journal of gastroenterology.

[8]  C. Loddenkemper,et al.  Differential priming of CD8 and CD4 T‐cells in animal models of autoimmune hepatitis and cholangitis , 2007, Hepatology.

[9]  A. Czaja Autoimmune hepatitis. Part A: pathogenesis , 2007, Expert review of gastroenterology & hepatology.

[10]  R. Rosa,et al.  Effect of mycophenolate mofetil regimen on peripheral blood lymphocyte subsets in kidney transplant recipients. , 2003 .

[11]  A. González-Quintela,et al.  Total Serum IgE Levels in Chronic Hepatitis C: Influence of Interferon Alpha Therapy , 2001, International Archives of Allergy and Immunology.

[12]  A. A. Hassan.,et al.  T-helper subsets cytokine production in kidney transplant recipients: diverting influences and impact on graft outcome. , 2000, Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia.

[13]  F. Alvarez,et al.  Short-term cyclosporine induces a remission of autoimmune hepatitis in children. , 1999, Journal of hepatology.

[14]  E. Powell,et al.  Serum soluble CD23 but not IL8, IL10, GM-CSF, or IFN-gamma is elevated in patients with hepatitis C infection. , 1997, Clinical immunology and immunopathology.

[15]  G. Gerken,et al.  Autoreactive CD4+ LKM‐specific and anticlonotypic T‐cell responses in LKM‐1 antibody‐positive autoimmune hepatitis , 1996, Hepatology.

[16]  R. Williams,et al.  Azathioprine for long-term maintenance of remission in autoimmune hepatitis. , 1995, The New England journal of medicine.

[17]  B. Fleischer,et al.  Analysis of the in vitro cytokine production by liver‐infiltrating T cells of patients with autoimmune hepatitis , 1993, Clinical and experimental immunology.

[18]  H. Boehmer,et al.  Lymphocyte lineage commitment: Instruction versus selection , 1993, Cell.

[19]  D. Vergani,et al.  Class I and class II major histocompatibility complex antigen expression on hepatocytes: A study in children with liver disease , 1990, Hepatology.

[20]  I. Cohen,et al.  Control of experimental autoimmune encephalomyelitis by T cells responding to activated T cells. , 1989, Science.

[21]  M. Fritzler,et al.  Serum immunoglobulin E levels in patients with primary biliary cirrhosis. , 1989, The Journal of allergy and clinical immunology.

[22]  H. Wekerle,et al.  Suppression of experimentally induced autoimmune encephalomyelitis by cytolytic T–T cell interactions , 1988, Nature.

[23]  I. Cohen,et al.  Anti-idiotypic network induced by T cell vaccination against experimental autoimmune encephalomyelitis. , 1988, Science.

[24]  S. Poppema,et al.  CELLULAR AND HUMORAL IMMUNE-REACTIONS IN CHRONIC ACTIVE LIVER-DISEASE .1. LYMPHOCYTE SUBSETS IN LIVER BIOPSIES OF PATIENTS WITH UNTREATED IDIOPATHIC AUTOIMMUNE HEPATITIS, CHRONIC ACTIVE HEPATITIS-B AND PRIMARY BILIARY-CIRRHOSIS , 1982 .

[25]  M. Manns,et al.  989 BUDESONIDE 3MG TID IS SUPERIOR TO PREDNISONE IN COMBINATION WITH AZATHIOPRINE IN THE TREATMENT OF AUTOIMMUNE HEPATITIS , 2008 .

[26]  F. Villamil,et al.  Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis. , 1999 .

[27]  G. Schönrich,et al.  Multiple levels of peripheral tolerance. , 1993, Immunology today.