Intrahepatic IgG/IgM plasma cells ratio helps in classifying autoimmune liver diseases

Cabibi, Daniela; Tarantino, Giuseppe; Barbaria, F.; Campione, Maria; Craxı̀, Antonio; Marco, Vito Di

doi:10.1016/j.dld.2009.12.006

Cited by 29 publications

(23 citation statements)

References 16 publications

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“…Furthermore, we used CD138, a highly sensitive and specific marker of plasma cells, for rapid and precise localization of plasma cells, unlike the previous reports. Recent reports suggest that the IgM/IgG ratio could be used to distinguish PBC from AIH [10,11]. This is supported by our results, which revealed a significantly higher IgM/IgG ratio in patients with PBC compared to those with AIH or OS (0.2, 2.0, and 0.3, P \ 0.005).…”

Section: Discussionsupporting

confidence: 91%

“…Plasma cells are characteristically found in AIH, but are also commonly present in PBC. Recent studies have shown that it is possible to distinguish AIH from PBC with periportal plasmacytic infiltrates by IgG and IgM immunohistochemistry (IHC) [8][9][10][11]. Although most immunohistochemical markers are not completely satisfactory for use in histological biopsy sections, some have the potential to improve the specificity and sensitivity of plasma cell detection, including CD138 antibodies [12].…”

Section: Introductionmentioning

confidence: 99%

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The utility of IgG, IgM, and CD138 immunohistochemistry in the evaluation of autoimmune liver diseases

Abe

Takahashi

Nozawa³

et al. 2014

Med Mol Morphol

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Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) present with distinct clinical features. The term "PBC-AIH overlap syndrome (OS)" has been adopted to describe the condition characterized by occurrence of both PBC and AIH, although this clinical entity is difficult to define. This study aimed to assess the utility of IgG, IgM, and CD138 immunohistochemistry in the evaluation of AIH, PBC, and OS. Immunohistochemistry was performed with anti-human IgG, IgM, and CD138 to detect specific plasma cells in the liver. Predominant IgG staining was observed in AIH (85.7 %), while equivocal (46.1 %) or predominant (38.5 %) IgM staining was observed in PBC. In OS, equivocal (20 %) or predominant (80 %) IgG staining was observed. The IgM/IgG ratio was significantly higher in PBC than in AIH or OS (P < 0.005). Histological findings revealed significantly higher IgM expression in PBC at cholangitis activity grades 2-3 compared to those at cholangitis activity grades 0-1. In contrast, a significantly higher IgG expression was observed in PBC at hepatitis activity and fibrosis grades 2-3 compared to those at hepatitis activity and fibrosis grades 0-1. Taken together, periportal plasmacytic infiltrates with variable immunohistochemistry patterns of IgG and IgM expression characterized different autoimmune liver diseases.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

The utility of IgG, IgM, and CD138 immunohistochemistry in the evaluation of autoimmune liver diseases

Abe

Takahashi

Nozawa³

et al. 2014

Med Mol Morphol

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“…Unfortunately, results of staining for IgG and IgM in putative cases AIH-PBC overlap were inconsistent, and the specificity and sensitivity of immunostaining to detect AIH or PBC were low [114]. Importantly, PBC was exclusively associated with a ratio of IgG to IgM expressing plasma cells < 1, while a ratio > 1 was present in the patients with putative AIH overlap [115].…”

Section: Aih-pbc Overlap Syndromementioning

confidence: 92%

“…A recent cross-sectional study reported that Hispanic patients with PBC had a significantly increased prevalence of overlap syndrome compared with non-Hispanic PBC patients (31% vs. 13%; P = 0.002) [113], suggesting an ethnic predisposition. Immunohistochemical staining of plasma cells expressing IgG or IgM in liver biopsies has been proposed as an aid in the diagnosis of AIH-PBC overlap [114,115]. Plasma cells predominantly express IgG in AIH and IgM in PBC; thus, concurrent expression of both would suggest overlap.…”

Section: Aih-pbc Overlap Syndromementioning

confidence: 99%

Autoimmune hepatitis

Sahebjam

Vierling

2015

Front. Med.

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Autoimmune hepatitis is a chronic liver disease putatively caused by loss of tolerance to hepatocyte-specific autoantigens. It is characterized by female predilection, elevated aminotransferase levels, autoantibodies, increased γ-globulin or IgG levels and biopsy evidence of interface hepatitis. It is currently divided into types 1 and 2, based on expression of autoantibodies. Autoantigenic epitopes have been identified only for the less frequent type 2. Although autoimmune hepatitis occurs in childhood, this review focuses on disease in adults. In the absence of pathognomonic biomarkers, diagnosis requires consideration of clinical, biochemical, serological and histological features, which have been codified into validated diagnostic scoring systems. Since many features also occur in other chronic liver diseases, these scoring systems aid evaluation of the differential diagnosis. New practice guidelines have redefined criteria for remission to include complete biochemical and histological normalization on immunosuppressive therapy. Immunosuppression is most often successful using prednisone or prednisolone and azathioprine; however, the combination of budesonide and azathioprine for non-cirrhotic patients offers distinct advantages. Patients failing standard immunosuppression are candidates for alternative immunosuppressive regimens, yet none of the options has been studied in a randomized, controlled trial. Overlap syndromes with either primary sclerosing cholangitis or primary biliary cirrhosis occur in a minority. Liver transplantation represents a life-saving option for patients presenting with acute liver failure, severely decompensated cirrhosis or hepatocellular carcinoma. Transplant recipients are at risk for recurrent autoimmune hepatitis in the allograft, and de novo disease may occur in patients transplanted for other indications. Patients transplanted for AIH are also at risk for recurrent or de novo inflammatory bowel disease. Progress in our understanding of the immunopathogenesis should lead to identification of specific diagnostic and prognostic biomarkers and new therapeutic strategies.

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“…Another study reported that the frequency of HLA-DR7 was increased in AIH-PBC overlap, possibly conferring increased susceptibility [36]. Immunostaining of liver biopsies for plasma cells expressing IgG or IgM was proposed as an aid in the diagnosis of PBC-AIH overlap [37,38]. Plasma cells in AIH predominantly express IgG, while plasma cells in PBC predominant express IgM.…”

Section: Overlap Syndromesmentioning

confidence: 99%

Diagnosis and Treatment of Autoimmune Hepatitis

Vierling

2011

Curr Gastroenterol Rep

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Autoimmune hepatitis is a chronic liver disease characterized by elevated aminotransferase levels, autoantibodies, increased γ-globulin or IgG levels and biopsy evidence of interface hepatitis. Recent advances include new practice guidelines that redefine criteria for remission to require complete biochemical and histological normalization on therapy; comparisons between the revised original and simplified diagnostic scoring systems; refined characterization of autoantibodies and their diagnostic performance parameters; proof of the safety and efficacy of combination budesonide and azathioprine therapy for non-cirrhotic patients; scrutiny of overlap syndromes; further analyses of the outcomes of orthotopic liver transplantation and the diagnosis and treatment of recurrent and de novo autoimmune hepatitis after transplantation. Anticipated consequences of the application of the new definition of therapeutic remission include a reduction in the proportion of patients achieving remission with conventional immunosuppression regimens and a corresponding increase in the need for alternative therapies.

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Intrahepatic IgG/IgM plasma cells ratio helps in classifying autoimmune liver diseases

Abstract: Immunostaining for IgM and IgG plasma cells on liver tissue can be a valuable parameter for better diagnosis of autoimmune liver disease and also for variant or mixed syndromes.

Cited by 29 publications

References 16 publications

The utility of IgG, IgM, and CD138 immunohistochemistry in the evaluation of autoimmune liver diseases

The utility of IgG, IgM, and CD138 immunohistochemistry in the evaluation of autoimmune liver diseases

Autoimmune hepatitis

Diagnosis and Treatment of Autoimmune Hepatitis

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