Molecular features of somatic reversion and EBV infection in XLP patients
| XLP patient | Age at analysis | Clinical features | Current status | Original mutation | Reversion | Reversion mutation | % SAP+ cells in PBMCs | EBV status |
| yr | % | |||||||
| 1 | 36–47 | •Clinical EBV: severe (19 yr) | •Deceased (age 49 yr) | c.161A>G; Y54C | Yes | c.161G>A; C54Y | 4.42 | + |
| •HLH: yes (49 yr) | ||||||||
| •Lymphoma: B-cell lymphoma, large bowel (10 yr) | ||||||||
| •Hypogamma: yes (19 yr) | ||||||||
| •Other: meningitis (19 yr), lymphoproliferation of CD4+CD8+ T cells (40 yr) | ||||||||
| 2 | 38–45 | •Clinical EBV: mild (17 yr) | •Stable | c.259T>C; F87S | Yes | c.259C>T/A; S87Y; S87F | 8.45 | + |
| •HLH: nil | •On IVIg | |||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: yes (26 yr) | ||||||||
| 3 | 42–52 | •Clinical EBV: mild (20 yr) | •Stable | c.259T>C; F87S | Yes | c.259C>A; S87Y | 2.29 | + |
| •HLH: nil | •On IVIg | |||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: yes (21 yr) | ||||||||
| 5 | 11–17 | •Clinical EBV: nil | •Stable | c.251T>C; I84T | Yes | c.251C>T; T84I | 1.67 | + |
| •HLH: nil | ||||||||
| •Lymphoma: B-cell lymphoma | ||||||||
| •Hypogamma: nil | ||||||||
| 8 | 16 | •Clinical EBV: severe (10-12 yr); severe reactivation (21 yr) | •BMT (age 21 yr) | c.251T>C; I84T | Yes | c.251C>T; T84I | 1.63 | + |
| •HLH: nil | •Stable | |||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: yes (13 yr) | ||||||||
| 10 | 31 | •Clinical EBV: nil | •Deceased (age 31 yr) | c.163C>T; R55X | Yes | c.163T>A/C; X55R | 1.82 | + |
| •HLH: yes (26 yr) | ||||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: nil | ||||||||
| •Other: vasculitis | ||||||||
| 11 | 34 | •Clinical EBV: fulminant | •Stable | Deletion | No | NA | Nil | + |
| •HLH: nil | •On IVIg | |||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: nil | ||||||||
| •Other: psoriasis, chronic active hepatitis, IBD | ||||||||
| 23 | 38 | •Clinical EBV: severe (12 yr) | •Deceased (age 37 yr) | ND | Yes | ND | 1.94 | + |
| •HLH: nil | ||||||||
| •Lymphoma: unknown | ||||||||
| •Hypogamma: yes (16 yr) | ||||||||
| 24 | 3 | •Clinical EBV: fulminant (3 yr) | •Stable 3 yr after BMT | c.3G>T; M1I | No | NA | <LOD | + (acute infection) |
| •HLH: yes (3 yr) | ||||||||
| •Lymphoma: possible non-Hodgkin’s lymphoma (3 yr) | ||||||||
| •Hypogamma: unknown | ||||||||
| 25 | 17 | •Clinical EBV: nil | •Stable 2 yr after BMT | c.3G>T; M1I | No | NA | <LOD | − |
| •HLH: nil | ||||||||
| •Lymphoma: small bowel lymphoma (12 yr) | ||||||||
| •Hypogamma: yes | ||||||||
| 26 | 11 | •Clinical EBV: nil | •Stable | c.160T>C; Y54H | Yes | Below limit of sensitivity | 0.01 | + |
| •HLH: nil | •On IVIg | |||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: yes (7 yr) | ||||||||
| 27 | Cord blood | •Clinical EBV: nil | •Deceased | c.163C>T; R55X | No | NA | <LOD | − |
| •HLH: nil | ||||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: nil |
| XLP patient | Age at analysis | Clinical features | Current status | Original mutation | Reversion | Reversion mutation | % SAP+ cells in PBMCs | EBV status |
| yr | % | |||||||
| 1 | 36–47 | •Clinical EBV: severe (19 yr) | •Deceased (age 49 yr) | c.161A>G; Y54C | Yes | c.161G>A; C54Y | 4.42 | + |
| •HLH: yes (49 yr) | ||||||||
| •Lymphoma: B-cell lymphoma, large bowel (10 yr) | ||||||||
| •Hypogamma: yes (19 yr) | ||||||||
| •Other: meningitis (19 yr), lymphoproliferation of CD4+CD8+ T cells (40 yr) | ||||||||
| 2 | 38–45 | •Clinical EBV: mild (17 yr) | •Stable | c.259T>C; F87S | Yes | c.259C>T/A; S87Y; S87F | 8.45 | + |
| •HLH: nil | •On IVIg | |||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: yes (26 yr) | ||||||||
| 3 | 42–52 | •Clinical EBV: mild (20 yr) | •Stable | c.259T>C; F87S | Yes | c.259C>A; S87Y | 2.29 | + |
| •HLH: nil | •On IVIg | |||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: yes (21 yr) | ||||||||
| 5 | 11–17 | •Clinical EBV: nil | •Stable | c.251T>C; I84T | Yes | c.251C>T; T84I | 1.67 | + |
| •HLH: nil | ||||||||
| •Lymphoma: B-cell lymphoma | ||||||||
| •Hypogamma: nil | ||||||||
| 8 | 16 | •Clinical EBV: severe (10-12 yr); severe reactivation (21 yr) | •BMT (age 21 yr) | c.251T>C; I84T | Yes | c.251C>T; T84I | 1.63 | + |
| •HLH: nil | •Stable | |||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: yes (13 yr) | ||||||||
| 10 | 31 | •Clinical EBV: nil | •Deceased (age 31 yr) | c.163C>T; R55X | Yes | c.163T>A/C; X55R | 1.82 | + |
| •HLH: yes (26 yr) | ||||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: nil | ||||||||
| •Other: vasculitis | ||||||||
| 11 | 34 | •Clinical EBV: fulminant | •Stable | Deletion | No | NA | Nil | + |
| •HLH: nil | •On IVIg | |||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: nil | ||||||||
| •Other: psoriasis, chronic active hepatitis, IBD | ||||||||
| 23 | 38 | •Clinical EBV: severe (12 yr) | •Deceased (age 37 yr) | ND | Yes | ND | 1.94 | + |
| •HLH: nil | ||||||||
| •Lymphoma: unknown | ||||||||
| •Hypogamma: yes (16 yr) | ||||||||
| 24 | 3 | •Clinical EBV: fulminant (3 yr) | •Stable 3 yr after BMT | c.3G>T; M1I | No | NA | <LOD | + (acute infection) |
| •HLH: yes (3 yr) | ||||||||
| •Lymphoma: possible non-Hodgkin’s lymphoma (3 yr) | ||||||||
| •Hypogamma: unknown | ||||||||
| 25 | 17 | •Clinical EBV: nil | •Stable 2 yr after BMT | c.3G>T; M1I | No | NA | <LOD | − |
| •HLH: nil | ||||||||
| •Lymphoma: small bowel lymphoma (12 yr) | ||||||||
| •Hypogamma: yes | ||||||||
| 26 | 11 | •Clinical EBV: nil | •Stable | c.160T>C; Y54H | Yes | Below limit of sensitivity | 0.01 | + |
| •HLH: nil | •On IVIg | |||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: yes (7 yr) | ||||||||
| 27 | Cord blood | •Clinical EBV: nil | •Deceased | c.163C>T; R55X | No | NA | <LOD | − |
| •HLH: nil | ||||||||
| •Lymphoma: nil | ||||||||
| •Hypogamma: nil |
BMT, BM transplant; HLH, hemophagocytic lymphohistiocytosis; hypogamma, hypogammaglobulinemia; IVIg, intravenous Ig; LOD, limit of detection by flow cytometry; NA, not applicable. XLP2 and XLP3 are siblings; XLP5 and XLP8 are first cousins. The values in parentheses indicate age of presentation of each clinical feature. EBV load was determined by quantitative PCR.