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      Study of nonstandard auto-antibodies as prognostic markers in auto immune hepatitis in children

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          Abstract

          Background

          Antibodies to chromatin and soluble liver antigen have been associated with severe form of autoimmune hepatitis and/or poor treatment response and may provide guidance in defining subsets of patients with different disease behaviors. The major clinical limitation of these antibodies is their lower individual occurrence in patients with autoimmune hepatitis.

          Aim

          To estimate the value of detection of these non-standard antibodies in autoimmune hepatitis as prognostic markers.

          Methods

          Both antibodies were tested by enzyme immunoassay in 20 patients with autoimmune hepatitis.

          Results

          Antibodies to soluble liver antigen were not detected in any of our patients. On the other hand anti chromatin antibodies were present in 50% (10/20). Antibodies to chromatin occurred more commonly in females than males (8/14 versus 2/6). Of the 14 patients who relapsed 8(57%) had antichromatin antibodies while they were present in only 2 out of 6(33.3%) non relapsers. Antichromatin antibodies were found more in patients with antinuclear (3/4) and anti smooth muscle antibodies (9/13) more than in those with liver kidney microsomal antibodies (1/4) and those seronegative (1/4) i.e. they were +ve in patients with type I (8/12(66.6%)) more than those with type II (1/4(25%)) and those seronegative (1/4(25%)). Antibodies to chromatin are associated with high levels of γ globulin but yet with no statistical difference between seropositive and seronegative counterparts (p = 0.65).

          Conclusion

          Antibodies to chromatin may be superior than those to soluble liver antigen in predicting relapse and may be useful as prognostic marker. Further studies with larger number of patients and combined testing of more than one antibody will improve the performance parameters of these antibodies and define optimal testing conditions for them before they can be incorporated into management algorithms that project prognosis.

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          Most cited references27

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          International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis.

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            Autoimmune hepatitis in childhood: a 20-year experience.

            To determine the clinical, biochemical, and histological features, and outcome of childhood autoimmune hepatitis (AIH), we reviewed the medical records of 52 children with AIH, 32 (median age: 10 [2-15] years) anti-nuclear and/or smooth muscle antibody (ANA/SMA) positive, 20 (7 [0.8-14] years) liver/kidney microsomal antibody (LKM-1) positive, with median follow-up of 5 years (range 0.3-19). At presentation: 56% had symptoms of prolonged acute hepatitis; LKM-1 positive were younger (P = .011), with higher bilirubin (P = .007), and AST (P = .047); ANA/SMA positive had lower albumin (P = .023); 69% ANA/SMA positive, and 38% LKM-1 positive were cirrhotic (P = .080). ANA/SMA positive had increased frequency of HLA haplotype A1/B8/DR3/DR52a compared with controls (53% vs. 14%, P < .001). Of six (5 LKM-1 positive) with fulminant hepatitis, four were transplanted, one died, and one ANA/SMA positive improved with immunosuppression. Of 47 treated with immunosuppression, 2 (1 LKM-1 positive) died with no remission and 4 (2 LKM-1 positive) were transplanted 8 to 14 years after diagnosis. Immunosuppression was stopped successfully in 19% of ANA/SMA positive after a median of 3 years of treatment, but in none of LKM-1 positive. Baseline bilirubin and international normalized prothrombin ratio (INR) were independent variables predictive of outcome. In conclusion, ANA/SMA positive and LKM-1 positive AIH in childhood have clinical, biochemical, and histological differences, but similar severity and long-term outcome.
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              Aetiopathogenesis of autoimmune hepatitis.

              Interface hepatitis, histological hallmark of autoimmune hepatitis (AIH), is a dense portal mononuclear cell infiltrate invading the parenchyma, consisting of CD4 and CD8 T-lymphocytes, monocytes/macrophages and plasma cells. What triggers AIH is unknown, but there is evidence that failure of immune homeostasis plays a permissive role allowing liver autoantigen-specific cells to attack hepatocytes. Damage is likely to be orchestrated by CD4 T-lymphocytes recognizing an autoantigenic liver peptide. For autoimmunity to arise, the peptide, embraced by an HLA class II molecule, must be presented to naïve CD4 T-helper (T(H)0) cells by professional antigen-presenting cells. Once activated, T(H)0 cells can differentiate into T(H)1 cells, which are pivotal to macrophage activation, enhance HLA class I expression, rendering liver cells vulnerable to CD8 T-cell attack, and induce HLA class II expression on hepatocytes; or into T(H)2 cells producing IL-4, IL-10 and IL-13, cytokines favouring autoantibody production by B-lymphocytes. Autoantigen recognition is tightly controlled by regulatory mechanisms, such as those exerted by CD4+CD25+ regulatory T-cells (T-regs). Numerical and functional T-reg impairment characterizes AIH, particularly during active disease. Advances in the study of autoreactive T-cells stem mostly from AIH type 2, where the main autoantigen, CYP2D6, is known enabling characterization of antigen-specific immune responses. Monocyte involvement in the autoimmune liver attack has been recently reported. Copyright 2009 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Ital J Pediatr
                Italian Journal of Pediatrics
                BioMed Central
                1824-7288
                2009
                20 July 2009
                : 35
                : 22
                Affiliations
                [1 ]Department of Pediatrics, Ain Shams University, Cairo, Egypt
                [2 ]Department of Clinical Pathology, Ain Shams University, Cairo, Egypt
                Article
                1824-7288-35-22
                10.1186/1824-7288-35-22
                2720979
                19712439
                f3baa4ef-a12b-421c-9b7c-24f31d030d50
                Copyright © 2009 El- Din Elshazly et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 May 2009
                : 20 July 2009
                Categories
                Review

                Pediatrics
                Pediatrics

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