T-cell receptor Vβ repertoire analysis in patients with chronic idiopathic neutropenia demonstrates the presence of aberrant T-cell expansions

Chronic idiopathic neutropenia (CIN) is a bone marrow (BM) disorder characterized by presence of activated T-lymphocytes in peripheral blood (PB) and BM. We investigated the pattern of T-cell responses in CIN by analyzing the T-cell receptor β-chain variable (Vβ) gene repertoire. Compared to controls, CIN patients displayed different patterns of Vβ gene usage in PB CD3+, CD4+ and CD8+ cells. The frequency of Vβ skewing and the number of expanded Vβ families per subject were higher in patients compared to controls in all cell subpopulations. Skewing was more profound within the CD8+ cells. The number of Vβ expansions per patient was higher in BM compared to PB. The majority of patients displayed a skewed oligoclonal/monoclonal pattern within the PB and/or BM CD8+ cells and a polyclonal profile within the CD4+ cells. We concluded that aberrant T-cell expansions are invariably detected in CIN patients and may have a role in the disease pathogenesis.