High-throughput TCR sequencing reveals expansion of private clones associated with decreased TCR diversity in patients with ITP vs healthy controls: as clones expand, the platelet count falls. (A) The percentage of space occupied by the expanded clones (defined as clones occupying >5% of the repertoire) is significantly higher in patients with ITP than in healthy controls. (B) Number of productive unique CDR3 sequences (unique clones) per 103 unique clones is significantly lower in patients with ITP than in healthy controls. (C) Simpson diversity index is significantly lower in patients with ITP than in healthy controls. (D) In patients with refractory ITP, the percentage of space occupied by the expanded clones is significantly higher than in patients with nonrefractory ITP. (E) The number of productive unique clones per 103 unique CDR3 sequences (diversity) is reduced in patients with a platelet count of <30 × 109/L and recovers in individual patients as the count increases (platelet count of ≥30 × 109/L). (F) The amount of the T-cell repertoire/space taken up by expanded clones is higher in patients with a platelet count <30 × 109/L and falls in individual patients as the count returns to normal levels, reflecting the changes in T-cell repertoire. (G) In 2 patients with chronic ITP, individual clones were followed-up for over a number of years (point 0 is the first time that TCR is measured) and compared with the overall T-cell diversity and the platelet count. TCR diversity falls with the platelet count and increases as it recovers. Correspondingly, the individual clones expand as the platelet count decreases and contract as the platelet count increases. ∗P ≤ .05; ∗∗P ≤ .01; ∗∗∗P ≤ .001; ∗∗∗∗P ≤ .0001.
