Introduction
Material and methods
Patients
Gene and protein expression analyses
Analysis of lymphocyte subsets
Statistical analysis
Results
Clinical characteristics of patients with XLP
Patient | Age at onset (years) | Age at diagnosis (years) | Family history | Clinical presentation | EBV | IVIG | Allogenic HSCT (years) | Outcome | Age at death or current age (years) | SH2D1A mutation (protein) | SAP expression | Ref. |
---|---|---|---|---|---|---|---|---|---|---|---|---|
P1 | 1.42 | 1.5 | − | HLH, Hypo-γ | + | + | 2.65 | Alive | 2.92 | R55X | Deficient | This study |
P2 | 1.08 | 5.5 | − | Hypo-γ, LPD | + | + | − | Alive | 8.5 | R55X | Deficient | This study |
P3.1 | 7.0 | 12.0 | + | Hypo-γ, LPD | + | + | − | Alive | 14.42 | R55L | NE | This study |
P3.2 | 12.0 | 19.0 | + | Hypo-γ, LPD | Unknown | + | − | Alive | 20.42 | R55L | NE | This study |
P4 | 1.25 | 1.33 | − | HLH, Hypo-γ, encephalitis | + | + | − | Died of intracranial hemorrhage | 1.43 | L25fsX1 | Deficient | This study |
P5* | 4.00 | 4.5 | − | Recurrent IM | − | − | − | Alive | 9.92 | Y47fsX12 | Deficient | This study |
P6 | 2.08 | 3.00 | + | HLH | − | − | − | Alive | 8.67 | V40fsX34 | NE | This study |
P7 | 3.25 | 3.28 | − | HLH, encephalitis | + | − | − | Died of gastrointestinal hemorrhage | 3.38 | W64X | NE | This study |
P8 | 5 | 6 | + | Lymphoma, Hypo-γ | + | + | − | Died of lymphoma | 7 | R55X | Deficient | This study |
P9.1 | 1 | 9.83 | + | Hypo-γ, LPD | + | + | − | Alive | 12.5 | R55X | Deficient | This study |
P9.2 | 1 | 16.67 | + | Hypo-γ, LPD | + | + | − | Alive | 19.33 | R55X | Deficient | This study |
P10.1 | 0.08 | 14.83 | + | Hypo-γ, lymphoma | + | + | − | Alive | 17.33 | G93D | Deficient | This study |
P10.2 | 0.5 | 4.75 | + | Hypo-γ, LPD | + | + | − | Alive | 7.08 | G93D | Deficient | This study |
P11 | 4.00 | 4.08 | − | HLH, Hypo-γ | + | + | 4.08 | Alive | Unknown | L98P | NE | [37] |
P12 | 0.74 | 0.82 | − | HLH, encephalitis, MSOF | + | + | − | Died of MSOF | 0.81 | Y47fsX12 | NE | [37] |
P13 | 1.40 | 1.48 | − | HLH, encephalitis, MSOF | + | + | − | Died of MSOF | 1.5 | Y54C | NE | [37] |
P14 | 3.92 | 4.00 | + | HLH, Hypo-γ, MSOF | NE | + | − | Died of MSOF | Shortly after diagnosis | indels,138_201+18delinsGGTGAAAGAGGGTG | NE | [17] |
P15 | 3.00 | 5.00 | + | Hypo-γ, lymphoma | + | + | − | Died of hepatic coma | Shortly after diagnosis | Y54X | NE | [17] |
P16 | 0.92 | 9.00 | − | Hypo-γ, LPD | NE | + | − | Alive | Unknown | Y7C | NE | [17] |
P17 | 1.75 | 1.75 | + | HLH | + | / | − | Unknown | Unknown | R55X | NE | [46] |
P18 | 2.83 | 2.92 | − | HLH, LPD | + | + | − | Alive | Unknown | S35TfsX44 | NE | [13] |
P19 | 0.71 | 0.75 | + | HLH, LPD | + | + | − | Dead | 0.75 | T61TfsX19 | NE | [13] |
P20 | 1.21 | 1.25 | + | HLH, LPD | + | + | − | Dead | 1.25 | E67D | NE | [13] |
P21 | 1.13 | 1.17 | − | HLH, LPD | + | + | − | Dead | 1.71 | c.199_201+23del | NE | [13] |
P22 | 1.5 | 1.5 | / | HLH | NE | / | − | Unknown | Unknown | Y100X | NE | [22] |
P23 | 3.0 | 3.0 | / | HLH | NE | / | − | Unknown | Unknown | L31Rfs50X | NE | [45] |
P24 | / | 0.67 | / | HLH | / | / | / | Unknown | Unknown | R55X | NE | [6] |
P25 | / | 1.0 | / | HLH | / | / | / | Unknown | Unknown | c.199_201+23del | NE | [6] |
P26 | / | 1.0 | / | HLH | / | / | / | Unknown | Unknown | Y47VfsX21 | NE | [6] |
P27 | / | 1.0 | / | HLH | / | / | / | Unknown | Unknown | Del. Exon1-4 | NE | [6] |
P28 | / | 4.0 | / | HLH | / | / | / | Unknown | Unknown | Y76X | NE | [6] |
P29 | / | 5.0 | / | HLH | / | / | / | Unknown | Unknown | Del. Exon1-4 | NE | [6] |
P30 | / | 3.25 | / | HLH | / | / | / | Unknown | Unknown | W64X | NE | [5] |
P31 | / | 0.97 | / | HLH | / | / | / | Unknown | Unknown | Y54X | NE | [5] |
P32 | / | 0.95 | / | HLH | / | / | / | Unknown | Unknown | R55X | NE | [5] |
Patient | Age at onset (years) | Age at diagnosis (years) | Family history | Clinical presentation | Recurrent HLH | Splenomegaly | Hypo-γ | Colitis | EBV | Allogenic HSCT (years) | Current age (years) | XIAP mutation (protein) | XIAP expression | Ref |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
P33 | 5.33 | 5.5 | − | Recurrent respiratory infection | − | − | + | − | − | − | 7.75 | A321G | Normal | This study |
P34# | 0.67 | 1 | − | HLH | + | + | NE | − | NE | − | 3.08 | Y75C | Deficient | This study |
P35 | 2.75 | 3.75 | − | Neutropenia | − | − | − | − | − | − | 4.92 | D367G | Deficient | This study |
P36.1 | 0.04 | 1.92 | + | Leukocytosis, thrombocytopenia | − | + | − | − | − | − | Died of pneumorrhagia | A321G | Deficient | This study |
P36.2 | − | 12 | + | Asymptomatic | − | − | − | − | NE | − | 12.5 | A321G | NE | This study |
P37# | 4.33 | 4.42 | − | HLH | − | + | − | − | + | 4.77 | 5.25 | W317X | Deficient | This study |
P38# | 5 | 5.33 | − | HLH | + | + | − | − | + | − | 12.42 | Del. Exon 4 | Deficient | This study |
P39 | 0.08 | 1.33 | − | HLH | + | + | + | − | − | − | Unknown | T32fsX | NE | [17] |
P40 | 0.08 | 0.25 | − | HLH, MOSF | − | + | + | − | − | − | Died of MOSF | D367G | NE | [37] |
P41 | 4 | 4.58 | − | HLH | / | / | / | − | + | − | Unknown | c.1099 + 2T>C | NE | [44] |
P42 | 5.8 | 5.8 | − | HLH | − | + | + | − | − | 6.05 | Alive and well after HSCT | N341fsX348 | NE | [16] |
P43 | 5.1 | 6.1 | − | HLH, Crohn’s disease | + | + | − | + | − | − | Unknown | G304X | NE | [41] |
P44 | / | 0.33 | HLH | / | / | / | / | / | / | / | T308IfsX23 | NE | [6] | |
P45 | / | 1 | HLH | / | / | / | / | / | / | / | E349del | NE | [6] | |
P46 | / | 1 | HLH | / | / | / | / | / | / | / | Del.Exon3 | NE | [6] | |
P47 | / | 2 | HLH | / | / | / | / | / | / | / | D368EfsX23 | NE | [6] | |
P48 | / | 2 | HLH | / | / | / | / | / | / | / | R443H | NE | [6] | |
P49 | / | 2 | HLH | / | / | / | / | / | / | / | R443H | NE | [6] | |
P50 | / | 4 | HLH | / | / | / | / | / | / | / | Exonic deletion | NE | [6] | |
P51 | / | 5 | HLH | / | / | / | / | / | / | / | c.1099+2T>C | NE | [6] | |
P52 | / | 6 | HLH | / | / | / | / | / | / | / | D130GfsX11 | NE | [6] | |
P53 | / | 28 | HLH | / | / | / | / | / | / | / | R443H | NE | [6] |
Analysis of gene and protein expression in patients with XLP
Immunological characteristics of patients with XLP
Treatment of patients with XLP
Discussion
Spectrum of mutation analysis and associated phenotype
Age of onset and diagnosis
HLH
EBV infection
IBD
Lymphoma
Hypogammaglobulinemia
Our center (13) | China (35) | Kanegane (33) [19] | Seemayer (272) [34] | Booth (91) [4] | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Incidence | Mortality | Incidence | Mortality | Incidence | Mortality | Incidence | Mortality | Incidence | Mortality | |
HLH | 4/13 (30.8%) | 2/4 (50%) | 25/33 (75.8%) | 8/13 (61.5%) | 18/33 (55%) | 16/18 (89%) | 157/272 (58%) | 127/132 (96%) | 32/91 (35.2%) | 21/32 (65.6%) |
Lymphoma or LPD | 8/13 (61.5%) | 1/8 (12.5%) | #14/24 (58.3%) | 5/14 (35.7%) | 7/33 (21%) | 3/7 (43%) | 82/272 (30%) | 46/71 (65%) | 22/91 (24.2%) | 2/22 (9%) |
Hypo-γ | 10/13 (76.9%) | 2/10 (20%) | #14/24 (58.3%) | 4/14 (35.7%) | 12/33 (36%) | 4/11 (36%) | 84/272 (31%) | 34/75 (45%) | 46/91 (50.5%) | 6/46 (13.0%) |
Our center (7) | China (22) | ||||||
---|---|---|---|---|---|---|---|
HLH | 3/7 (42.9%) | 18/22 (81.8%) | 11 (64.7%) | 25 (71.4%) | 12 (36.4%) | 7 (63.6%) | 1 (11.1%) |
Recurrent HLH | 3/7 (42.9%) | # 4/12 (33.3%) | 10 (58.8%) | / | / | / | / |
EBV infection-associated HLH | 2/7 (28.6%) | # 3/12 (25%) | 4 (23.5%) | 20 (57.1%) | 8 (24.2%) | 4 (36.4%) | 1 (11.1%) |
Splenomegaly | 4/7 (57.1%) | # 8/12 (66.7%) | 6 (35.3%) | 18 (51.4%) | 19 (57.6%) | 4 (36.4%) | 6 (66.7%) |
Hypogammaglobulinemia | 1/7 (14.3%) | # 4/12 (33.3%) | 4 (18.2%) | 4 (11.4%) | 5 (15.2%) | 2 (18.2%) | 3 (33.3%) |
Lymphoma | 0/7 (0%) | # 0/12 (0%) | 0 (0%) | 0 (%) | 0 (0%) | 0 (0%) | 0 (0%) |
Colitis | 0/7 (0%) | # 1/12 (8.3%) | 6 (35.3%) | 8 (22.8%) | 10 (30.3%) | 4 (36.4%) | 3 (33.3%) |