Characteristics of patients enrolled in the study
| Patient | Sex | Age | Group | Histology (Marsh) | IEL count* | CD8 staining† | TCR-βF1 staining‡ | TCRβ clonality§ | TCRγ clonality§ | Tg-IgA serology | HLA-DQ¶ | Died of EATL | No. of reads** |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F | 49 | ACD | IIIC | 100 | Positive | – | Not clonal | Not clonal | Positive | DQ2.5-ho | – | 1 386 048 |
| 2 | M | 60 | ACD | IIIA | 100 | Positive | – | Not clonal | Not clonal | Positive | nd | – | 1 375 338 |
| 3A | F | 61 | ACD | IIIB | 52 | Positive | – | Not clonal | Not clonal | Positive | DQ2.5 | – | 1 492 114 |
| 3B | F | 65 | CD GFD | 0 | <25 | nd | – | Not clonal | Not clonal | Negative | – | 1 229 854 | |
| 4A | M | 64 | ACD | IIIA | 65 | Partially negative | – | A: clonal; | Clonal | Positive | DQ2.5-ho | – | 1 398 559 |
| B/C: not clonal | |||||||||||||
| 4B | M | 69 | ACD | IIIA | 61 | Partially negative | – | A: clonal; | Clonal | Positive | – | 1 109 972 | |
| B/C: not clonal | |||||||||||||
| 5A | M | 61 | ACD | IIIA | 52 | Positive | – | Not clonal | Not clonal | Positive | DQ2.5 | – | 3 838 298 |
| 5B | M | 61 | ACD | IIIA | 45 | Positive | – | Not clonal | Not clonal | Positive | – | 2 500 660 | |
| 6 | M | 59 | ACD | IIIB | 80 | Partially negative | – | B: clonal; | Not clonal | Positive | DQ2.5 | – | 2 914 869 |
| A/C: not clonal | |||||||||||||
| 7 | M | 55 | ACD | IIIA | 25 | Positive | – | B: clonal; | Not clonal | Positive | DQ2.5/2.2 | – | 1 166 697 |
| A/C: not clonal | |||||||||||||
| 8 | M | 82 | ACD | IIIA | 58 | Positive | – | Not clonal | Not clonal | Positive | DQ2.5/2.2 | – | 1 403 191 |
| 9 | F | 36 | ACD | IIIA | 70 | Positive | – | Not clonal | Not clonal | Positive | DQ2.5 | – | 1 056 191 |
| 10A | F | 51 | ACD | IIIA | 43 | Positive | – | Not clonal | Not clonal | Positive | DQ2.5 | – | 1 489 344 |
| 10B | F | 52 | CD GFD | 0 | <25 | nd | – | Not clonal | Not clonal | Negative | – | 1 819 643 | |
| 11 | F | 54 | CD GFD | I | 40 | Positive | – | B: clonal; | Clonal | Negative | DQ2.5 | – | 1 096 650 |
| A/C: not clonal | |||||||||||||
| 12 | F | 34 | CD GFD | I | 60 | nd | – | Not clonal | Not clonal | Negative | DQ2.5-ho | – | 1 429 008 |
| 13 | F | 44 | CD GFD | I | 50 | Positive | – | B: clonal; | Clonal | Negative | DQ8.5 | – | 2 120 940 |
| A/C: not clonal | |||||||||||||
| 14 | F | 47 | CD GFD | I | 38 | Positive | – | Not clonal | Not clonal | Negative | DQ8 | – | 1 389 764 |
| 15 | F | 44 | CD GFD | 0 | <25 | nd | – | Not clonal | Not clonal | Negative | DQ2.5 | – | 4 882 201 |
| 16 | M | 62 | CD GFD | I-II | 52 | nd | – | Not clonal | Not clonal | Negative | DQ6 | – | 1 232 456 |
| 17 | F | 36 | CD GFD | I | 67 | Positive | – | Not clonal | Not clonal | Negative | DQ2.5 | – | 1 767 305 |
| 18 | F | 29 | CD GFD | IIIA†† | 67 | Positive | – | Not clonal | Not clonal | Positive | DQ2.5/8 | – | 1 076 997 |
| 19 | F | 32 | CD GFD | IIIA†† | 47 | nd | – | B: clonal; | Not clonal | Negative | DQ2.5 | – | 2 867 422 |
| A/C: not clonal | |||||||||||||
| 20 | F | 42 | Control | 0 | <25 | nd | – | A/B: not clonal; C clonal | Not clonal | Negative | DQ6 | – | 1 587 356 |
| 21 | F | 50 | Control | 0 | <25 | nd | – | Not clonal | Not clonal | Negative | DQ2.5-ho | – | 1 661 085 |
| 22 | F | 20 | Control | 0 | <25 | nd | – | Not clonal | Not clonal | Negative | DQ2.5-ho | – | 2 001 279 |
| 23 | F | 30 | Control | 0 | <25 | nd | – | Clonal | Clonal | Negative | DQ6 | – | 1 169 960 |
| 24 | F | 22 | Control | 0 | <25 | nd | – | Not clonal | Not clonal | Negative | DQ6 | – | 1 370 690 |
| 25 | M | 43 | Control | 0 | <25 | nd | – | Not clonal | Not clonal | Negative | DQ6 | – | 564 245 |
| 26 | F | 20 | Control | 0 | <25 | nd | – | A: biallelic clonal; B/C: not clonal | Not clonal | Negative | DQ2.5 | – | 1 480 608 |
| 27 | F | 36 | Control | 0 | <25 | nd | – | Not clonal | Not clonal | Negative | DQ2.5 | – | 1 439 428 |
| 28 | F | 60 | Control | 0 | <25 | nd | – | Not clonal | Not clonal | Negative | DQ2.5 | – | 2 148 355 |
| 29 | M | 51 | RCD type I | IIIA | 35 | Positive | Positive | Not clonal | Not clonal | Negative | DQ6 | – | 1 289 891 |
| 30 | F | 60 | RCD type I | IIIB | 80 | Positive | Positive | Not clonal | Not clonal | Positive | DQ2.5 | – | 888 615 |
| 31 | M | 49 | RCD type I | IIIB | 69 | Positive | Partially negative | Not clonal | Not clonal | Negative | DQ8 | – | 1 711 745 |
| 32 | F | 45 | RCD type I | IIIA | 32 | Positive | Positive | Not clonal | Not clonal | Negative | DQ2.5-ho | – | 1 283 412 |
| 33 | F | 47 | RCD type I | IIIA | 51 | Positive | Partially negative | Not clonal | Not clonal | Negative | DQ7 | – | 1 022 807 |
| 34 | F | 75 | RCD type I | IIIB | 25 | Positive | negative | Not clonal | Not clonal | Negative | DQ8 | – | 839 327 |
| 35 | M | 73 | RCD type I | IIIA | 70 | Positive | Positive | Not clonal | Not clonal | Negative | DQ7 | – | 1 382 335 |
| 36‡‡ | F | 71 | RCD type I | IIIB | 81 | Negative | Positive | Not clonal | Clonal | Negative | DQ2.5 | – | 1 018 656 |
| 37 | M | 49 | RCD type II | IIIB | 54–63 | Negative | Partially negative | A/B: not clonal; | Not clonal | Positive | DQ2.5 | – | 975 336 |
| C clonal | |||||||||||||
| 38 | M | 67 | RCD type II | IIIA | 74 | Negative | Positive | Clonal | Clonal | Positive | DQ2.5-ho | Yes | 4 150 734 |
| 39 | F | 41 | RCD type II | IIIC | >25 | Negative | Partially negative | Clonal | Clonal | Negative | DQ2.5-ho | Yes | 4 261 385 |
| 40 | F | 69 | RCD type II | IIIC | nd | nd | Partially negative | Clonal | Biallelic clonal | nd | DQ2.5 | Yes | 2 283 715 |
| 41 | M | 75 | RCD type II | IIIB | 120 | Negative | Partially negative | Clonal | Clonal | Positive | DQ2.5-ho | Yes | 6 012 299 |
| 42 | F | 82 | RCD type II | IIIC | 52 | Positive | negative | Biallelic clonal | Not clonal | Positive | DQ2.5/8 | – | 4 045 900 |
| 43A§§ | F | 51 | RCD type II | IIIB | <25 | Negative | negative | Not clonal | Not clonal | Positive | DQ2.5-ho | – | 1 053 659 |
| 43B | F | 56 | RCD type II | IIIA | 68 | Negative | negative | Not clonal | Not clonal | Negative | 1 408 767 | ||
| 44 | M | 62 | RCD type II | IIIC | 87 | Negative | Positive | Biallelic clonal | Biallelic clonal | Negative | DQ8 | Yes | 4 965 878 |
| 45 | M | 56 | Marsh I | I | 80 | Positive | – | Not clonal | Biallelic clonal | Negative | DQ5 | – | 958 161 |
| 46 | F | 53 | Marsh I | I | 47 | Partially negative | – | Not clonal | Not clonal | Negative | DQ2.2 | – | 1 693 995 |
| 47 | F | 45 | Marsh I | I | 72 | Positive | – | A: biallelic clonal; B/C: not clonal | Biallelic clonal | Negative | DQ8 | – | 1 659 303 |
Patients labelled as ‘A’ and ‘B’ were analysed twice using duodenal mucosa sampled at distinct gastroscopies.
*Counted per 100 enterocytes.
†Positive: >50% of CD3-T-cells are CD8+.
‡Positive: IHC detection of TCR on CD3-T-cells.
§Determined by GeneScan (BIOMED-2 TCRβ primer sets A/B and C; TCRγ primer sets A and B), detailed TCRβ GeneScan results are provided in the online supplementary material I.
¶DQ2.5, heterozygous for DQ2.5, DQ2.5-ho, homozygous for HLA-DQ2.5, DQ2.5/2.2, heterozygous for DQ2.5 and DQ2.2.
**Number of analysed sequence reads, a mean of 1.9×106 reads per sample guaranteed a 130-fold coverage of single TCRβ sequences (100 ng DNA input≙∼14.500 T-cells).
††Significant improvement on a GFD. Further disease course showed complete remission.
‡‡Classification as RCD type I was made on the basis of lack of clonality of TCR-β GeneScan and positivity of TCR-βF1 immunostaining.
§§Patient 43 had previously been TCRγ-monoclonal and thus been categorised as RCD type II and treated accordingly.
ACD, active coeliac disease; CD, coeliac disease; EATL, enteropathy-associated T-cell lymphoma; GFD, gluten-free diet; IEL, intraepithelial lymphocytes; IHC, immunohistochemistry; nd, not determined; RCD, refractory coeliac disease; TCR, T-cell receptor; Tg-IgA, transglutaminase-IgA serology.