NK activity, perforin expression, and proportion of NK cells in PBMCs of ALPS/DALD patients carrying the N252S and A91V perforin variations
. | Effector-target ratios for NK activity† . | . | . | Perforin expression‡ . | . | Peripheral-blood NK cells, % . | . | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Subjects according to PRF1 variation* . | 100:1 . | 30:1 . | 10:1 . | % . | MFI . | CD3-CD16+ . | CD3-CD56+ . | ||||
| N252S | |||||||||||
| ALPS-5 | 58 | 49 | 38 | 6§ | 9§ | 11 | 16 | ||||
| ALPS-11 (12 years) | 35 | 26 | 18 | 24 | 50 | 13 | 15 | ||||
| (5 years) | 7§ | 4§ | 2§ | nd | nd | nd | nd | ||||
| (3 years) | 3§ | 1§ | 0§ | nd | nd | nd | nd | ||||
| A91V | |||||||||||
| DALD-3 | 13 | 12 | 3 | 45 | 62 | 8 | 8 | ||||
| DALD-6 | 28 | 12 | 3 | 15§ | 61 | 13 | 13 | ||||
| DALD-10 | 18 | 11 | 4 | 36 | 17§ | 9 | 13 | ||||
| Median | 18 | 12 | 3 | 36 | 61 | 9 | 13 | ||||
| Controls∥ | 31 (13-56) | 23 (6-35) | 12 (2-31) | 23 (17-26) | 47 (28-74) | 11 (5-31) | 17 (4-27) | ||||
. | Effector-target ratios for NK activity† . | . | . | Perforin expression‡ . | . | Peripheral-blood NK cells, % . | . | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Subjects according to PRF1 variation* . | 100:1 . | 30:1 . | 10:1 . | % . | MFI . | CD3-CD16+ . | CD3-CD56+ . | ||||
| N252S | |||||||||||
| ALPS-5 | 58 | 49 | 38 | 6§ | 9§ | 11 | 16 | ||||
| ALPS-11 (12 years) | 35 | 26 | 18 | 24 | 50 | 13 | 15 | ||||
| (5 years) | 7§ | 4§ | 2§ | nd | nd | nd | nd | ||||
| (3 years) | 3§ | 1§ | 0§ | nd | nd | nd | nd | ||||
| A91V | |||||||||||
| DALD-3 | 13 | 12 | 3 | 45 | 62 | 8 | 8 | ||||
| DALD-6 | 28 | 12 | 3 | 15§ | 61 | 13 | 13 | ||||
| DALD-10 | 18 | 11 | 4 | 36 | 17§ | 9 | 13 | ||||
| Median | 18 | 12 | 3 | 36 | 61 | 9 | 13 | ||||
| Controls∥ | 31 (13-56) | 23 (6-35) | 12 (2-31) | 23 (17-26) | 47 (28-74) | 11 (5-31) | 17 (4-27) | ||||
nd indicates not determined.
All patients were heterozygous for the indicated variation except for DALD-10, who was homozygous.
NK activity is expressed as specific cell-lysis percent, and it is the mean of triplicate assays, whose standard deviation was always < 10% of the mean. Spontaneous cell lysis was always < 10% of maximal cell lysis.
Perforin expression is shown as percentage of positive cells and mean fluorescence intensity (MFI) in arbitrary units.
< 5th percentile of controls.
Median (5th-95th percentile range) from 10 controls. The NK activity of these DALD patients was significantly lower than that of the controls (P = .015, Mann-Whitney test).