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

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Abstract
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] Vβ 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 Vβ 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 antigen-driven T-cell expansion in HAA and achievement of a normal T-cell repertoire during recovery from HAA. (Blood. 2004;103:4588-4593)

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