(Very) Severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V)SAA is a bone marrow failure syndrome characterized by immune mediated destruction of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder, in 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 of TCR Vß CDR3 region, which is refered to as TCR Vß skewing. We investigated the value of TCR Vß repertoire analysis in pediatric MDS-RC and (v)SAA patients. Peripheral blood and/or bone marrow mononuclear samples of patients with (v)SAA (n=38), MDS-RC (n=28) and 18 controls were analysed with Vß heteroduplex analysis of extracted RNA. Skewing was found in 21/38 (55%) of the (v)SAA patients and in 17/28 (61%) of the RC patients. Seventeen patients with clinical (v)SAA showed no oligoclonality. A significant difference in TCR skewing was found between the (v)SAA + MDS-RC patients as compared to the controls (χ2 analysis, p=0.001), but not between MDS-RC and (v)SAA (χ2 analysis, p=0.8). In this study paired samples (PB and BM) of 25 cases showed a high correlation between the skewing results in both compartments (Pearson correlation, rr 0.98). In this study TCR Vß repertoire analysis did not discriminate between MDS-RC and (v)SAA. Prospective studies will be necessary to investigate whether there is a role for this molecular tool in pediatric MDS-RC for the identification of a subset of patients that is associated with auto-immunity and therfore could be treated with IST up-front, and whether it can be used for molecular response monitoring.

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