T cell receptor VB repertoire diversity in patients with immune thrombocytopenia following splenectomy.
In recent years, a pathophysiological role for T cells in immune thrombocytopenia (ITP) has been established. We applied cDNA size distribution analysis of the T cell receptor (TCR) beta-variable (VB) complementarity-determining region 3 (CDR3) in order to investigate T cell repertoire diversity among immune thrombocytopenia patients who had either responded or not responded to splenectomy, and compared them to normal controls. ITP patients who had had a durable platelet response to splenectomy showed a mean 2.8 +/- 2.1 abnormal CDR3 size patterns per patient, similar to healthy volunteers (2.9 +/- 2.0 abnormal CDR3 size patterns). In contrast, patients unresponsive to splenectomy demonstrated evidence of significantly more clonal T cell expansions than patients who had responded to splenectomy or controls (11.3 +/- 3.3 abnormal CDR3 size patterns per patient; P < 0.001). Of the VB subfamilies analysed, VB3 and VB15 correlated with response or non-response to splenectomy, each demonstrating oligoclonality in non-responding patients (P < 0.05). These findings suggest that removal of the spleen may lead directly or indirectly to reductions in T cell clonal expansions in responders, or that the extent of T cell clonality impacts responsiveness to splenectomy in patients with ITP.
Fogarty
P F
PF
Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1652, USA.
Rick
M E
ME
Zeng
W
W
Risitano
A M
AM
Dunbar
C E
CE
Bussel
J B
JB
D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D005260:Female; D019674:Genes, T-Cell Receptor beta; D014644:Genetic Variation; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000032:analysis; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013156:Splenectomy; D013921:Thrombocytopenia / Q000276:immunology* / Q000601:surgery; D017211:Treatment Failure
D007135:Immunoglobulin Variable Region; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D012313:RNA