Oligoclonal T cell expansion in myelodysplastic syndrome: evidence for an autoimmune process.
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 Vbeta profiles in the MDS patients compared with controls. In peripheral blood T cells, 60/345 Vbeta profiles examined were skewed in MDS patients compared with 3/115 Vbeta profiles in TD controls (P<0.0001), and 58/460 Vbeta profiles in age-matched controls (P=0.05). A study of Jbeta region within the skewed Vbeta profiles revealed preferential usage of Jbeta 2.1 in MDS in contrast with a wide distribution over the entire Jbeta 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.
Epperson
D E
DE
Bone Marrow Transplant Unit, Hematology Branch, National Heart, Lung and Blood Institute, National Institute of Health, 2000 Rockville Pike, Building 10, Rm. 7C 103, Bethesda, MD 20892, USA.
Nakamura
R
R
Saunthararajah
Y
Y
Melenhorst
J
J
Barrett
A J
AJ
D000328:Adult; D000367:Age Factors; D000368:Aged; D015551:Autoimmunity; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology*; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*
D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta