Oligoclonal T cell expansion in myelodysplastic syndrome: evidence for an autoimmune process

Abstract 

There is accumulating evidence that the marrow-failure of myelodysplastic syndrome (MDS) is immune-mediated. We studied patients with MDS to look for oligoclonal or clonal expansion in T cells indicative of an autoimmune process. We used a PCR-based technique (spectratyping) to characterize the T cell repertoire in MDS (n=15; 9 RA, 4 RARS, 2 RAEB) and compared results with age-matched healthy donors (n=20) and transfusion-dependent (TD) patients with hemoglobinopathy (n=5). We found a significantly higher number of skewed Vβ profiles in the MDS patients compared with controls. In peripheral blood T cells, 60/345 Vβ profiles examined were skewed in MDS patients compared with 3/115 Vβ profiles in TD controls (P<0.0001), and 58/460 Vβ profiles in age-matched controls (P=0.05). A study of Jβ region within the skewed Vβ profiles revealed preferential usage of Jβ 2.1 in MDS in contrast with a wide distribution over the entire Jβ spectrum in controls, consistent with non-random T cell clonal expansion in MDS. These findings provide further evidence that T cell mediated immune processes are a feature of MDS.

Keywords:  Myelodysplastic syndrome, T cell repertoire, T cell receptor, Spectratyping, Immunosuppressive treatment

Abbreviations:  ATG, antithymocyte globulin, LGL, large granular lymphocyte, MDS, myelodysplastic syndrome, RA, refractory anemia, RARS, refractory anemia with ring sideroblasts, RAEB, refractory anemia with excess blasts, SAA, severe aplastic anemia, TCR, T cell receptor, TD, transfusion-dependent