Clinical presentation of 80 pES patients according to genetic subgroups
| . | M+, N = 52 . | M−, N = 28 . | P, M+ vs M− . | Pathogenic, N = 32 . | Probably pathogenic, N = 20 . | P, pathogenic vs probably pathogenic . |
|---|---|---|---|---|---|---|
| Consanguinity, % (n) | 16 (9) | 7 (2) | 19 (6) | 15 (3) | ||
| Immune manifestations in first-degree relatives, % (n) | 37 (19) | 18 (5) | .08 | 44 (14) | 25 (5) | |
| Immune manifestations in extended relatives, % (n) | 50 (26) | 30 (8) | .06 | 57 (18) | 38 (8) | |
| Sex ratio (F/M) | 0.7 | 0.6 | 0.8 | 0.7 | ||
| Median age at first episode of cytopenia (min-max), y | 5.2 (0.5-15.2) | 7.1 (0.3-15.6) | 6.8 (0.5-15.2) | 4.1 (0.8-14.7) | ||
| Associated immunopathological manifestations, % (n) | 92 (48) | 64 (18) | .001 | 97 (31) | 85 (17) | |
| Median age at first immunopathologic manifestation (min-max), y | 5.3 (0.3-14.9) | 8.6 (1.6-17.2) | 5.0 (0.3-14.9) | 5.5 (0.8-17.7) | ||
| Median no. of immunopathologic manifestations (min-max) | 2.5 (0-8) | 1 (0-6) | .007 | 3 (0-8) | 2 (0-4) | |
| Median age at immunological disease onset (ES or IM) (min-max), y | 3.3 (0.3-14.7) | 6.0 (0.3-15.6) | 3.9 (0.3-14.1) | 2.6 (0.8-14.7) | ||
| Lymphoproliferation, % (n) | 58 (30) | 35 (10) | .06 | 63 (20) | 50 (10) | |
| Hypogammaglobulinemia, % (n) | 56 (29) | 29 (8) | .02 | 60 (19) | 50 (10) | |
| Autoimmune/autoinflammatory organ disease, % (n) | 56 (29) | 32 (9) | .04 | 63 (20) | 45 (9) | |
| Liver and digestive tract manifestations, % | 13 | 2 | .051 | 12 | 1 | .008 |
| Lung manifestations, % | 10 | 2 | 9 | 1 | .07 | |
| Neurologic manifestations, % | 8 | 2 | 5 | 3 | ||
| Skin manifestations, % | 6 | 4 | 5 | 1 | ||
| Rheumatologic manifestations, % | 3 | 1 | 2 | 1 | ||
| Endocrinologic manifestations, % | 3 | 0 | 2 | 1 | ||
| Atopy, % (n) | 25 (13) | 7 (2) | .07 | 28 (9) | 20 (4) | |
| SLE biomarkers,* % (n) | 17 (9) | 36 (10) | 16 (5) | 20 (4) | ||
| ALPS biomarkers† % (n) | 19 (10) | 7 (3) | 28 (9) | 5 (1) | .07 | |
| Severe or recurrent infections, % (n) | 50 (26) | 43 (12) | 57 (18) | 40 (8) | ||
| Median follow-up from first cytopenia (min-max), y | 9.6 (0.9-25.0) | 7.0 (0.2-26.5) | 9.2 (0.9-25.0) | 10.2 (4.2-20.8) | ||
| Need for second-line treatments, % (n) | 81 (42) | 63 (18) | 88 (28) | 70 (14) | ||
| Median no. of second-line treatments (min-max) | 2 (0-9) | 1 (0-5) | .02 | 2 (0-9) | 2 (0-6) | |
| Deaths, % (n) | 12 (6) | 0 (0) | .086 | 12 (4) | 10 (2) |
| . | M+, N = 52 . | M−, N = 28 . | P, M+ vs M− . | Pathogenic, N = 32 . | Probably pathogenic, N = 20 . | P, pathogenic vs probably pathogenic . |
|---|---|---|---|---|---|---|
| Consanguinity, % (n) | 16 (9) | 7 (2) | 19 (6) | 15 (3) | ||
| Immune manifestations in first-degree relatives, % (n) | 37 (19) | 18 (5) | .08 | 44 (14) | 25 (5) | |
| Immune manifestations in extended relatives, % (n) | 50 (26) | 30 (8) | .06 | 57 (18) | 38 (8) | |
| Sex ratio (F/M) | 0.7 | 0.6 | 0.8 | 0.7 | ||
| Median age at first episode of cytopenia (min-max), y | 5.2 (0.5-15.2) | 7.1 (0.3-15.6) | 6.8 (0.5-15.2) | 4.1 (0.8-14.7) | ||
| Associated immunopathological manifestations, % (n) | 92 (48) | 64 (18) | .001 | 97 (31) | 85 (17) | |
| Median age at first immunopathologic manifestation (min-max), y | 5.3 (0.3-14.9) | 8.6 (1.6-17.2) | 5.0 (0.3-14.9) | 5.5 (0.8-17.7) | ||
| Median no. of immunopathologic manifestations (min-max) | 2.5 (0-8) | 1 (0-6) | .007 | 3 (0-8) | 2 (0-4) | |
| Median age at immunological disease onset (ES or IM) (min-max), y | 3.3 (0.3-14.7) | 6.0 (0.3-15.6) | 3.9 (0.3-14.1) | 2.6 (0.8-14.7) | ||
| Lymphoproliferation, % (n) | 58 (30) | 35 (10) | .06 | 63 (20) | 50 (10) | |
| Hypogammaglobulinemia, % (n) | 56 (29) | 29 (8) | .02 | 60 (19) | 50 (10) | |
| Autoimmune/autoinflammatory organ disease, % (n) | 56 (29) | 32 (9) | .04 | 63 (20) | 45 (9) | |
| Liver and digestive tract manifestations, % | 13 | 2 | .051 | 12 | 1 | .008 |
| Lung manifestations, % | 10 | 2 | 9 | 1 | .07 | |
| Neurologic manifestations, % | 8 | 2 | 5 | 3 | ||
| Skin manifestations, % | 6 | 4 | 5 | 1 | ||
| Rheumatologic manifestations, % | 3 | 1 | 2 | 1 | ||
| Endocrinologic manifestations, % | 3 | 0 | 2 | 1 | ||
| Atopy, % (n) | 25 (13) | 7 (2) | .07 | 28 (9) | 20 (4) | |
| SLE biomarkers,* % (n) | 17 (9) | 36 (10) | 16 (5) | 20 (4) | ||
| ALPS biomarkers† % (n) | 19 (10) | 7 (3) | 28 (9) | 5 (1) | .07 | |
| Severe or recurrent infections, % (n) | 50 (26) | 43 (12) | 57 (18) | 40 (8) | ||
| Median follow-up from first cytopenia (min-max), y | 9.6 (0.9-25.0) | 7.0 (0.2-26.5) | 9.2 (0.9-25.0) | 10.2 (4.2-20.8) | ||
| Need for second-line treatments, % (n) | 81 (42) | 63 (18) | 88 (28) | 70 (14) | ||
| Median no. of second-line treatments (min-max) | 2 (0-9) | 1 (0-5) | .02 | 2 (0-9) | 2 (0-6) | |
| Deaths, % (n) | 12 (6) | 0 (0) | .086 | 12 (4) | 10 (2) |
Bold values represent P < .05, considered statistically significant.
ALPS, autoimmune lymphoproliferative syndrome; F, female; IM, immunopathological manifestation; M, male; M+, patients with mutations; M−, patients without detected mutations; SLE, systemic lupus erythematosus.
SLE biomarkers: antinuclear antibodies titer >1/160 on 2 separate samples, isolated significant autoantibodies.
ALPS biomarkers: persistent hypergammaglobulinemia (at least 2 SD over the mean for age), high counts of circulating TCR ab CD4−CD8− double-negative T lymphocytes.