Aplastic anaemia patients with clonal X-chromosome inactivation pattern in haemopoietic cells exhibit polyclonal TCRγ and IgH gene rearrangements

Previously, we reported that 13/18 (72%) female patients with aplastic anaemia (AA) exhibited a clonal X-chromosome inactivation (XCI) pattern in all haemopoietic lineages. To study the consequences of a clonal haemopoiesis for the randomness of immunoreceptor rearrangements in lymphocytes we determined clonality of T-cell receptor gamma (TCRγ) and immunoglobulin heavy chain (IgH) gene rearrangements in purified cell fractions. Peripheral blood granulocytes, monocytes, and B and T lymphocytes from 18 female patients in remission from AA were studied by PCR for randomness of XCI and rearrangement at the IgH and TCRγ locus. 13 patients were informative at the phosphoglycerate kinase-1 (PGK 1 ) and monoamine oxidase A (MAOA) loci. Five of them displayed an clonal XCI pattern in all lineages studied and one patient had a clonal XCI in all lineages, except the T cells. In three cases skin biopsies were also available. exhibiting a polyclonal pattern in two of them, and a reversed skewed pattern in the third. Analysis of the rearrangement patterns at the immunoreceptor loci revealed a polyclonal ladder of bands, irrespective of XCI status in the lymphocyte populations. These results demonstrate that in AA a clonal XCI pattern of the lymphoid compartment is compatible with a polyclonal immunoreceptor rearrangement pattern.