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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4588-4593.
Prepublished online as a Blood First Edition Paper on February 26, 2004; DOI 10.1182/blood-2003-11-3959.

Submitted November 18, 2003
Accepted February 9, 2004
Analysis of T cell repertoire in hepatitis-associated aplastic anemia
Jun Lu, Atanu Basu, J J Melenhorst, Neal S Young, and Kevin E Brown*
Hematology Branch, National Heart Lung and Blood Institute, Bethesda, MD, USA
* Corresponding author; email: brownk{at}nhlbi.nih.gov.
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 intra-hepatic lymphocytes in HAA patients by TCR spectratyping. In 6/7 HAA liver samples a broad skewing pattern in the 21 V[beta] 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 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.

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