T-cell receptor Vβ CDR3 oligoclonality frequently occurs in childhood refractory cytopenia (MDS-RC) and severe aplastic anemia

(Very) severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V) SAA is a bone marrow (BM) failure syndrome characterized by immune-mediated destruction of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder, of which the hypoplastic variant is, in case of absence of a cytogenetic clone, difficult to separate from (v) SAA. Recently, studies provided a molecular signature of autoimmunity in adult (v) SAA, by showing oligoclonality based on the length of the TCR V beta CDR3 region. We investigated retrospectively the frequency and the discriminative value of TCR V beta CDR3 oligoclonality in pediatric (v) SAA and MDS patients. Peripheral blood (PB) and/or BM mononuclear cell samples of pediatric patients with (v) SAA (n=38), refractory cytopenia (MDS-RC) (n=28) and 18 controls were analysed via TCR V beta heteroduplex PCR analysis of extracted RNA. A skewed TCR V beta CDR3 repertoire was found in 21/38 (v) SAA and in 17/28 RC patients in contrast to 2/18 in the control group. These data suggest an overlapping group of RC and SAA patients that may share a common immune-mediated pathogenesis. Prospective studies are required to establish the clinical value of TCR V beta CDR3 repertoire analysis to predict the clinical response in these patients.