T cell repertoire in the liver of patients with primary biliary cirrhosis

Inada, Haruhiko; Yoshizawa, Kaname; Ôta, Masao; Katsuyama, Yoshihiko; Ichijo, Tetsuya; Umemura, Takeji; Tanaka, Eiji; Kiyosawa, Kendo

doi:10.1016/s0198-8859(00)00129-4

Cited by 16 publications

(12 citation statements)

References 31 publications

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“…Second, spectratypes were scored mathematically, as previously described. 17,23 Evidence of oligoclonal expansion or skewing was assessed by calculating the relative fluorescence intensity (RI) of each peak (RI [%] ϭ 100 ϫ clonal peak area Ϭ total peak area). A skewed profile was determined if either (1) a single peak was observed and the RI of the dominant peak was greater than 35% of total peak area; (2) 2 dominant peaks were present and each peak's RI was greater than 25% of total peak area; or (3) there were multipeaks with the dominant peaks differing from a Gaussian pattern and the RI of the peaks was greater than 25% of total peak area.…”

Section: Analysis Of Spectratypementioning

confidence: 99%

Analysis of T-cell repertoire in hepatitis-associated aplastic anemia

Basu

Melenhorst

et al. 2004

Blood

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Hepatitis-associated aplastic anemia (HAA) is a syndrome of bone marrow failure following an acute attack of seronegative hepatitis. Clinical features and liver histology suggest a central role for an immune-mediated mechanism. To characterize the immune response, we investigated the T-cell repertoire (T-cell receptor [TCR] V ␤ chain subfamily) of intrahepatic lymphocytes in HAA patients by TCR spectratyping. In 6 of 7 HAA liver samples, a broad skewing pattern in the 21 V ␤ subfamilies tested was observed. In total, 62% ؎ 18% of HAA spectratypes showed a skewed pattern, similar to 68% ؎ 18% skewed spectratype patterns in 3 of 4 patients with confirmed viral hepatitis. Additionally, the T-cell repertoire had similarly low levels of complexity. In the peripheral blood lymphocytes (PBLs) of a separate group of HAA patients prior to treatment, 60% ؎ 15% skewed spectratypes were detected, compared with only 18% ؎ 8% skewed spectratypes in healthy controls. After successful immunosuppressive treatment, an apparent reversion to a normal T-cell repertoire with a corresponding significant increase in T-cell repertoire complexity was observed in the HAA samples. In conclusion, our data suggest an antigendriven T-cell expansion in HAA and achievement of a normal T-cell repertoire during recovery from HAA. IntroductionHepatitis-associated aplastic anemia (HAA), the development of hematopoietic failure with bone marrow hypocellularity within 6 months of an episode of hepatitis, is not uncommon, with hepatitis preceding the onset of bone marrow failure in 2% to 5% of aplastic anemia (AA) cases in Europe and the United States. 1 Aplastic anemia is also frequent following orthotopic liver transplantation for non-A, non-B, non-C hepatitis in young patients: 23% to 8% of non-A, non-B, non-C hepatitis patients receiving transplants developed aplastic anemia, compared with fewer than 1% of all liver transplant patients. 2,3 The hepatitis/aplastic anemia syndrome shows a stereotypical pattern; most often affecting young males, the hepatitis generally follows a benign course, but the onset of aplastic anemia 2 to 3 months later can be explosive and is usually fatal if untreated. 4 The presumed infectious cause of the hepatitis is unknown, but most cases are seronegative for known hepatitis viruses, including hepatitis A, B, C, and G (GB virus C[GBV-C]). [5][6][7] We previously reported 10 cases of HAA seen at the National Institutes of Health (NIH) that had evidence of lymphocyte activation; 70% responded to immunosuppression with antithymocyte globulin and cyclosporine. 8 Apart from case reports, the presence of lymphocyte activation, 9,10 and the clinical response to either immunosuppression or bone marrow transplantation, 11 little is known of the immunopathogenesis of this syndrome.The time interval between the occurrence of hepatitis and the onset of bone marrow failure suggests that the initial target organ of the immune response is the liver. For both hepatitis B and hepatitis C infection, large numbers of lymphocytes infilt...

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Section: Analysis Of Spectratypementioning

confidence: 99%

Analysis of T-cell repertoire in hepatitis-associated aplastic anemia

Basu

Melenhorst

et al. 2004

Blood

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“…16 Skewing of the T-cell VB spectrum has also been described for animal models of immunologically mediated diseases such as encephalitis 17,18 and thyroiditis. 19 In humans, expansion of specific CDR3 VB TCR clones has been found in type I diabetes mellitus, 20 thyroiditis, 21 rheumatoid arthritis, [22][23][24] primary biliary cirrhosis, 25 psoriasis, 26,27 or during graft-versus-host disease. 28 TCR VB repertoire analysis has also been performed in patients with AA, 12,13 myelodysplasia (MDS), 29 and paroxysmal nocturnal hemoglobinuria (PNH).…”

Section: Introductionmentioning

confidence: 99%

Changes in T-cell receptor VB repertoire in aplastic anemia: effects of different immunosuppressive regimens

Kook

Risitano

Zhang

et al. 2002

Blood

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We studied the degree and the pattern of skewing of the variable region of ␤-chain (VB) T-cell receptor (TCR) repertoire in aplastic anemia (AA) at initial presentation and after immunosuppression using a high-resolution analysis of the TCR VB complementarity-determining region 3 (CDR3). Age-matched healthy individuals and multitransfused patients with nonimmune-mediated hematologic diseases were used as controls. In newly diagnosed AA, the average frequency of CDR3 size distribution deviation indicative of oligoclonal T-cell proliferation was increased (44% ؎ 33% vs 9% ؎ 9%; P ‫؍‬ .0001); AA patients with human leukocyte antigen (HLA)-DR2 and those with expanded paroxysmal nocturnal hemoglobinuria clones showed more skewed VB repertoires. Nonrandom oligoclonal patterns were found for VB6, VB14-16, VB21, VB23, and VB24 subfamilies in more than 50%, and for VB15, VB21, and VB24 in more than 70% of AA patients with HLA-DR2. Patients received immunosuppression with antithymocyte globulin (ATG)/ cyclosporine (CsA) or cyclophosphamide (CTX) with CsA in combination, and their VB repertoire was reanalyzed after treatment. Whereas no significant change in the degree of VB skewing in patients who had received ATG was seen, patients treated with CTX showed a much higher extent of oligoclonality within all VB families, consistent with a profound and longlasting contraction of the T-cell repertoire. VB analysis did not correlate with the lymphocyte count prior to lymphocytotoxic therapy; however, after therapy the degree of VB skewing was highly reflective of the decrease in lymphocyte numbers, suggesting iatrogenic gaps in the VB repertoire rather than the emergence of clonal dominance. Our data indicate that multiple specific clones mediate the immune process in AA. (Blood. 2002; 99:3668-3675)

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“…This was confirmed by immunostaining with anti-CD4 and anti-CD8 antibody not clear. Inada et al 7 investigated the T cell repertoire in the liver of PBC patients, and the results suggested that CD4ϩ T cells with V--4 and J--2.7 might play an important role in the pathogenesis of PBC, whereas CD8ϩ T cells with V--17 and J--2.1 appeared to be important in antigen recognition in some patients. Thus, CD4ϩ T cells and CD8ϩ T cells both play a role in patients with SS or PBC.…”

Section: Discussionmentioning

confidence: 99%

Abacterial prostatitis and primary biliary cirrhosis with Sj�gren?s syndrome

Yasuda

Ogura

Horita

et al. 2004

Modern Rheumatology

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In patients with Sjögren's syndrome (SS), the salivary and lacrimal glands are often affected, although other epithelial tissues can become inflamed. Here, we report the first case of abacterial prostatitis in a patient with SS complicated by primary biliary cirrhosis. Histologically, the distribution and subpopulation of infiltrating lymphocytes were similar in the salivary gland, liver, and prostate. Treatment with steroid was successful. We speculate that the prostate may be one of the target organs in SS.

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T cell repertoire in the liver of patients with primary biliary cirrhosis

Cited by 16 publications

References 31 publications

Analysis of T-cell repertoire in hepatitis-associated aplastic anemia

Analysis of T-cell repertoire in hepatitis-associated aplastic anemia

Changes in T-cell receptor VB repertoire in aplastic anemia: effects of different immunosuppressive regimens

Abacterial prostatitis and primary biliary cirrhosis with Sj�gren?s syndrome

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