APLASTIC-ANEMIA PATIENTS WITH CLONAL X-CHROMOSOME INACTIVATION PATTERN IN HEMATOPOIETIC-CELLS EXHIBIT POLYCLONAL TCR-GAMMA AND IGH GENE REARRANGEMENTS

Previously, we reported that 13/18 (72%) female patients with aplastic anaemia (AA) exhibited a clonal X-chromosome inactivation (XCI) patte rn in all haemopoietic lineages. To study the consequences of a clonal haemopoiesis for the randomness of immunoreceptor rearrangements in l ymphocytes we determined clonality of T-cell receptor gamma (TCR gamma ) 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 TCR gam ma 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 c lonal XCI in all lineages, except the T cells. In three cases skin bio psies were also available, exhibiting a polyclonal pattern in two of t hem, and a reversed skewed pattern in the third. Analysis of the rearr angement patterns at the immunoreceptor loci revealed a polyclonal lad der of bands, irrespective of XCI status in the lymphocyte populations , These results demonstrate that in AA a clonal XCI pattern of the lym phoid compartment is compatible with a polyclonal immunoreceptor rearr angement pattern.