Table 1.
Clinical and molecular characteristics of nine ALPS patients with mutations in the CD95 death domain
| Patient ID number | Nucleotide change | Amino acid change | CD4−/CD8− αβ T cells, % (<1.0%) | Anti-CD3ɛ apoptosis*, % (50–70%) | Anti-CD95 apoptosis*, % (70–90%) | NMR structure | Disease manifestations† |
|---|---|---|---|---|---|---|---|
| 3 | A915C | Thr-225-Pro | 15 | 14 | 35 | Disrupted | LY, SM, AIHA, NP |
| 5 | C1011T | Gln-257-STOP | 18 | 33 | 25 | Disrupted | LY, SM, AIHA, ITP, NP |
| 6 | C966A | Ala-241-Asp | 13 | 8 | 21 | Intact | LY, HSM, AIHA |
| 17 | T1123G | Ile-294-Ser | 11 | 9 | 18 | Disrupted | LY, HSM, AIHA, NP |
| 26 | A975T | Asp-244-Val | ND | 16 | 1 | Intact | LY, HSM, AIHA |
| 29 | G943A | Arg-234-Gln | 2.2 | 15 | 18 | Intact | LY, SM, AIHA |
| 30 | ΔT1074 | Leu-278-STOP | 7.4 | ND | 5 | ND | LY, HSM, AIHA, ITP, GN, NP |
| 31 | G943C | Arg-234-Pro | 2.3 | ND | 5 | Disrupted | LY, SM, AIHA |
| 33 | C1020T | Gln-260-STOP | 5.7 | 22 | 17 | Disrupted | LY, SM, AIHA |
Assays performed on PHA-stimulated peripheral blood lymphocytes as described in Materials and Methods. The percent apoptosis induced in T cells from normal subjects under these assay conditions is shown in parentheses. All values reported are the results of the propidium iodide incorporation assay with the exception of the anti-CD95 assay on patient 30, which were done by the DNA content assay as described in ref. 23. ND, not determined.
LY, lymphadenopathy; SM, splenomegaly; HSM, hepatosplenomegaly; AIHA, autoimmune hemolytic anemia; ITP, immune thrombocytopenic purpura; GN, glomerulonephritis, and NP, autoimmune neutropenia; direct antiglobulin—note that Coomb’s test was positive in all patients.