Association of clonal T-cell large granular lymphocyte disease and paroxysmal nocturnal haemoglobinuria (PNH): further evidence for a pathogenetic link between T cells, aplastic anaemia and PNH

Br J Haematol. 2001 Dec;115(4):1010-4. doi: 10.1046/j.1365-2141.2001.03172.x.

Abstract

There is mounting evidence to suggest that T-cell-mediated suppression of haemopoiesis is a pathogenetic mechanism in three bone marrow failure syndromes: aplastic anaemia (AA), paroxysmal nocturnal haemoglobinuria (PNH) and myelodysplasia (MDS). T-cell microclones can be detected by sensitive polymerase chain reaction (PCR)-based methods in all three disorders. Recently, larger clonal populations of T-cell large granular lymphocytes (T-LGLs) have been observed in some patients with AA and MDS. Here, we report the development of a large clonal T-LGL population in a patient with bona fide PNH. In this patient, we defined part of the sequence of the T-cell receptor (TCR) beta-chain gene, and we have shown that the large T-LGL population emerged from a background of multiple smaller T-cell clones. Thus, T-LGL clones in AA, MDS and PNH probably expand as a result of antigenic stimulation. It is postulated that the antigen driving clonal T-cell proliferations in these disorders exists on haemopoietic stem cells.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anemia, Aplastic / immunology
  • Cell Division
  • Clone Cells
  • Coculture Techniques
  • Female
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / pathology
  • Hemoglobinuria, Paroxysmal / genetics
  • Hemoglobinuria, Paroxysmal / immunology*
  • Humans
  • Leukemia, T-Cell / complications*
  • Leukemia, T-Cell / genetics
  • Leukemia, T-Cell / immunology
  • Polymerase Chain Reaction / methods
  • T-Lymphocytes / pathology*