Background
Methods
Patients and control subjects
Genotyping
Genotyping by allele-specific PCR
Genotyping by sequencing
Flow cytometry for analysis of the Th1/Th2 ratio
Statistical analysis
Results
Patients’ characteristics
No. of patients (female/male) | 126 | (92/34) |
Age (years) at diagnosis, range (median) | 2.4–82.3 | (47.7) |
Platelet count (×109/L) at diagnosis, range (median) | 1.0–96.0 | (20.0) |
Mild thrombocytopenia, no. of cases (%) | 28 | (22.2) |
Moderate thrombocytopenia, no. of cases (%) | 28 | (22.2) |
Severe thrombocytopenia, no. of cases (%) | 40 | (31.7) |
Very severe thrombocytopenia, no. of cases (%) | 30 | (23.8) |
Minimum platelet count (×109⁄L), mean ± SD | 18.8 | ±18.0 |
Bleeding tendency, no. of cases (%) | 80 | (63.5) |
Severe bleeding tendency, no of cases (%) | 3 | (2.4) |
Severe ITP, no. of cases (%) | 24 | (19.0) |
Treatment, no. of cases (%) | 98 | (77.8) |
Prednisolone, no. of cases (%) | 82 | (65.1) |
Splenectomy, no. of cases (%) | 19 | (15.1) |
Eradication of Helicobacter pylori, no. of cases (%) | 43 | (34.1) |
Genotype and allele frequencies of IFN-γ, IFN-γR, IL-4, and IL-4Rα polymorphism in patients with cITP and healthy controls
ITP (%) | Control (%) |
P value | OR | 95%CI | Statistical model | |||
---|---|---|---|---|---|---|---|---|
IFN-γ | Genotype | TT | 3 (2.4) | 2 (1) | 0.38 | 2.44 | 0.40–14.80 | Recessive |
TA | 15 (11.9) | 44 (21.8) | ||||||
AA | 108 (85.7) | 156 (77.2) | 0.06 | 1.77 | 0.97–3.22 | Dominant | ||
Alleles | T | 21 (8.3) | 48 (11.9) | 0.15 | 0.67 | 0.39–1.16 | ||
A | 231 (91.7) | 356 (88.1) | 1.48 | 0.87–2.54 | ||||
FN-γR | Genotypes | GG | 0 (0) | 0 (0) | - | - | - | |
GA | 11 (8.7) | 22 (10.9) | ||||||
AA | 115 (91.3) | 180 (89.1) | 0.53 | 1.28 | 0.60–2.73 | Dominant | ||
Alleles | G | 11 (4.4) | 22 (5.4) | 0.54 | 0.79 | 0.38–1.66 | ||
A | 241 (95.6) | 382 (94.6) | 1.26 | 0.60–2.65 | ||||
IL-4 | Genotypes | CC | 17 (13.5) | 17 (8.4) | 0.14 | 1.70 | 0.83–3.46 | Recessive |
CT | 56 (44.4) | 88 (43.6) | ||||||
TT | 53 (42.1) | 97 (48.0) | 0.29 | 0.79 | 0.50–1.23 | Dominant | ||
Alleles | C | 90 (35.7) | 122 (30.2) | 0.14 | 1.28 | 0.92–1.79 | ||
T | 162 (64.3) | 282 (69.8) | 0.78 | 0.56–1.09 | ||||
IL-4Rα | Genotypes | QQ | 88 (69.8) | 161 (79.7) | 0.04 | 0.59 | 0.35–0.98 | Dominant |
QR | 37 (29.4) | 37 (18.3) | ||||||
RR | 1 (0.8) | 4 (2.0) | 0.65 | 0.40 | 0.04–3.58 | Recessive | ||
Alleles | Q | 213 (84.5) | 359 (88.9) | 0.11 | 0.69 | 0.43–1.09 | ||
R | 39 (15.5) | 45 (11.1) | 1.46 | 0.92–2.32 |
The clinical characteristics of the patients with cITP and the treatment response according to IFN-γ, IFN-γR, IL-4, and IL-4Rα polymorphisms
IFN-γ AA | IFN-γ non-AA | IFN-γR AA | IFN-γR non-AA | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
N
| (%) |
N
| (%) |
P value | OR | 95% CI |
N
| (%) |
N
| (%) |
P value | OR | 95% CI | |
No. of patients (%) | 108 | (85.7) | 18 | (14.3) | 115 | (91.3) | 11 | (8.7) | ||||||
Female patients, no. of cases (%) | 82 | (75.9) | 10 | (55.6) | 0.09 | 2.52 | 0.90–7.06 | 84 | (73.0) | 8 | (72.7) | 1.00 | 1.02 | 0.25–4.08 |
Age (years) at diagnosis, range (median) | 2.4–81.9 | (49.0) | 5.0–82.3 | (37.7) | 0.25 | 2.4–82.3 | (46.0) | 19.9–79.0 | (60.9) | 0.20 | ||||
Platelet count (×109/L) at diagnosis, mean ± SD | 30.8 | ± 24.9 | 21.9 | ± 20.7 | 0.15 | 29.9 | ± 24.6 | 25.8 | ± 22.8 | 0.60 | ||||
Mild thrombocytopenia, no. of cases (%) | 26 | (24.1) | 2 | (11.1) | 0.36 | 2.54 | 0.55–11.77 | 26 | (22.6) | 2 | (18.2) | 1.00 | 1.32 | 0.27–6.47 |
Moderate thrombocytopenia, no. of cases (%) | 24 | (22.2) | 4 | (22.2) | 1.00 | 1.00 | 0.30–3.32 | 25 | (21.7) | 3 | (27.3) | 0.71 | 0.74 | 0.18–3.00 |
Severe thrombocytopenia, no. of cases (%) | 35 | (32.4) | 5 | (27.8) | 0.79 | 1.25 | 0.41–3.77 | 37 | (32.2) | 3 | (27.3) | 1.00 | 1.27 | 0.32–5.05 |
Very severe thrombocytopenia, no. of cases (%) | 23 | (21.3) | 7 | (38.9) | 0.13 | 0.43 | 0.15–1.22 | 27 | (23.5) | 3 | (27.3) | 0.72 | 0.82 | 0.20–3.30 |
Minimum platelet count (×109⁄L), mean ± SD | 19.4 | ± 18.9 | 12.9 | ± 10.7 | 0.045 | 18.2 | ± 17.6 | 21 | ± 23.1 | 0.63 | ||||
Bleeding tendency, no. of cases (%) | 69 | (63.9) | 11 | (61.1) | 0.80 | 1.13 | 0.40–3.14 | 73 | (63.5) | 7 | (63.6) | 1.00 | 0.99 | 0.28–3.59 |
IL-4 CC | IL-4 non-CC | IL-4Rα QQ | IL-4Rα non-QQ | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
N
| (%) |
N
| (%) |
P value | OR | 95% CI |
N
| (%) |
N
| (%) |
P value | OR | 95% CI | |
No. of patients (%) | 17 | (13.5) | 109 | (86.5) | 88 | (69.8) | 38 | (30.2) | ||||||
Female patients, no. of cases (%) | 16 | (94.1) | 76 | (69.7) | 0.04 | 6.95 | 0.88–54.57 | 65 | (73.9) | 27 | (71.1) | 0.74 | 1.15 | 0.49–2.69 |
Age (years) at diagnosis, range (median) | 10.5–82.3 | (49.1) | 2.4–81.9 | (47.4) | 0.85 | 2.4–82.3 | (46.6) | 17.1–79.2 | (54.9) | 0.16 | ||||
Platelet count (×109/L) at diagnosis, mean ± SD | 24.5 | ± 22.4 | 30.3 | ± 24.7 | 0.36 | 29.8 | ± 24.8 | 28.9 | ± 23.9 | 0.84 | ||||
Mild thrombocytopenia, no. of cases (%) | 3 | (17.6) | 25 | (22.9) | 0.76 | 0.72 | 0.19–2.71 | 18 | (20.5) | 10 | (26.3) | 0.47 | 0.72 | 0.30–1.75 |
Moderate thrombocytopenia, no. of cases (%) | 3 | (17.6) | 25 | (22.9) | 0.76 | 0.72 | 0.19–2.71 | 22 | (25.0) | 6 | (15.8) | 0.35 | 1.78 | 0.66–4.82 |
Severe thrombocytopenia, no. of cases (%) | 6 | (35.3) | 34 | (31.2) | 0.78 | 1.20 | 0.41–3.52 | 26 | (29.5) | 14 | (36.8) | 0.42 | 0.72 | 0.32–1.60 |
Very severe thrombocytopenia, no. of cases (%) | 5 | (29.4) | 25 | (22.9) | 0.55 | 1.40 | 0.45–4.36 | 22 | (25.0) | 8 | (21.1) | 0.82 | 1.25 | 0.50–3.13 |
Minimum platelet count (×109⁄L), mean ± SD | 16.4 | ± 19.7 | 18.8 | ±17.8 | 0.61 | 17.5 | ± 17.4 | 20.8 | ± 19.4 | 0.35 | ||||
Bleeding tendency, no. of cases (%) | 11 | (64.7) | 69 | (63.3) | 1.00 | 1.06 | 0.37–3.09 | 55 | (62.5) | 25 | (65.8) | 0.73 | 0.87 | 0.39–1.92 |
IFN-γ AA | IFN-γ non-AA | IFN-γR AA | IFN-γR non-AA | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
N
| (%) |
N
| (%) |
P value | OR | 95% CI |
N
| (%) |
N
| (%) |
P value | OR | 95% | |
All treatment, no. of cases (%) | 82 | (75.9) | 15 | (83.3) | 0.76 | 0.66 | 0.18–2.48 | 89 | (77.4) | 8 | (72.7) | 0.71 | 1.35 | 0.33–5.47 |
Second line treatment, no. of cases (%) | 33 | (30.6) | 4 | (22.2) | 0.58 | 1.54 | 0.47–5.03 | 33 | (28.7) | 4 | (36.4) | 0.73 | 0.70 | 0.19–2.57 |
Second line treatment, no. of cases (%) | ||||||||||||||
CR, no. of cases (%) | 57 | (69.5) | 11 | (73.3) | 1.00 | 0.83 | 0.24–2.86 | 64 | (71.9) | 4 | (50.0) | 0.23 | 2.56 | 0.59–11.03 |
RR (CR+R), no. of cases (%) | 79 | (96.3) | 13 | (86.7) | 0.17 | 4.05 | 0.62–26.62 | 85 | (95.5) | 7 | (87.5) | 0.36 | 3.04 | 0.30–30.98 |
Prednisolone therapy, no. of cases (%) | 68 | (63.0) | 14 | (77.8) | 0.29 | 0.49 | 0.15–1.58 | 76 | (66.1) | 6 | (54.5) | 0.51 | 1.62 | 0.47–5.66 |
Response to prednisolone therapy | ||||||||||||||
CR, no. of cases (%) | 37 | (54.4) | 8 | (57.1) | 1.00 | 0.90 | 0.28–2.86 | 42 | (55.3) | 3 | (50.0) | 1.00 | 1.24 | 0.23–6.52 |
RR (CR+R), no. of cases (%) | 63 | (92.6) | 11 | (78.6) | 0.13 | 3.44 | 0.72–16.49 | 68 | (89.5) | 6 | (100) | 1.00 | ||
Splenectomy, no. of cases (%) | 17 | (15.7) | 2 | (11.1) | 1.00 | 1.50 | 0.32–7.10 | 18 | (15.7) | 1 | (9.1) | 1.00 | 1.86 | 0.22–15.40 |
Response to splenectomy | ||||||||||||||
CR, no. of cases (%) | 10 | (58.8) | 1 | (50.0) | 1.00 | 1.43 | 0.08–26.90 | 11 | (61.1) | 0 | (0) | 0.42 | ||
RR (CR+R), no. of cases (%) | 13 | (76.5) | 1 | (50.0) | 0.47 | 3.25 | 0.16–64.61 | 14 | (77.8) | 0 | (0) | 0.26 | ||
Eradication of Helicobacter pylori, no. of cases (%) | 40 | (37.0) | 3 | (16.7) | 0.11 | 3.03 | 0.83–11.12 | 38 | (33.0) | 5 | (45.5) | 0.51 | 0.61 | 0.17–2.12 |
Response to eradication of Helicobacter pylori
| ||||||||||||||
CR, no. of cases (%) | 19 | (47.5) | 1 | (33.3) | 1.00 | 1.81 | 0.15–21.59 | 17 | (44.7) | 3 | (60.0) | 0.65 | 0.54 | 0.08–3.61 |
Severe ITP, no. of cases (%) | 23 | (21.3) | 1 | (5.6) | 0.19 | 4.60 | 0.58–36.41 | 22 | (19.1) | 2 | (18.2) | 1.00 | 1.07 | 0.22–5.28 |
Refractory ITP, no. of cases (%) | 9 | (8.3) | 1 | (5.6) | 1.00 | 1.55 | 0.18–12.99 | 9 | (7.8) | 1 | (9.1) | 1.00 | 0.85 | 0.10–7.40 |
Corticosteroid-dependent, no. of cases (%) | 30 | (28.8) | 7 | (41.2) | 0.40 | 0.58 | 0.20–1.66 | 35 | (30.4) | 2 | (18.2) | 0.72 | 1.84 | 0.37–9.13 |
IL4 CC | IL4 non-CC | IL4Rα QQ | IL4Rα non-QQ | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
N
| (%) |
N
| (%) |
P value | OR | 95% CI |
N
| (%) |
N
| (%) |
P value | OR | 95% CI | |
All treatment, no. of cases (%) | 14 | (82.4) | 83 | (76.1) | 0.76 | 1.39 | 0.37–5.22 | 71 | (80.7) | 26 | (68.4) | 0.10 | 2.08 | 0.87–4.97 |
Second line treatment, no. of cases (%) | 9 | (52.9) | 28 | (25.7) | 0.04 | 3.25 | 1.15–9.25 | 29 | (33.0) | 8 | (21.1) | 0.21 | 1.84 | 0.75–4.52 |
Response to all treatments | ||||||||||||||
CR, no. of cases (%) | 9 | (64.3) | 59 | (71.1) | 0.75 | 0.73 | 0.22–2.41 | 50 | (70.4) | 18 | (69.2) | 1.00 | 1.06 | 0.40–2.81 |
RR (CR+R), no. of cases (%) | 13 | (92.9) | 79 | (95.2) | 0.55 | 0.66 | 0.68–6.36 | 68 | (95.8) | 24 | (92.3) | 0.61 | 1.89 | 0.30–12.00 |
Prednisolone therapy, no. of cases (%) | 12 | (70.6) | 70 | (64.2) | 0.79 | 1.34 | 0.44–4.08 | 62 | (70.5) | 20 | (52.6) | 0.05 | 2.15 | 0.98–4.70 |
Response to prednisolone therapy | ||||||||||||||
CR, no. of cases (%) | 5 | (41.7) | 40 | (57.1) | 0.36 | 0.54 | 0.16–1.85 | 34 | (54.8) | 11 | (55.0) | 1.00 | 0.99 | 0.36–2.74 |
RR (CR+R), no. of cases (%) | 10 | (83.3) | 64 | (91.4) | 0.33 | 0.47 | 0.08–2.65 | 56 | (90.3) | 18 | (90.0) | 1.00 | 1.04 | 0.19–5.60 |
Splenectomy, no. of cases (%) | 5 | (29.4) | 14 | (12.8) | 0.14 | 2.83 | 0.87–9.24 | 15 | (17.0) | 4 | (10.5) | 0.43 | 1.75 | 0.54–5.66 |
Response to splenectomy | ||||||||||||||
CR, no. of cases (%) | 4 | (80.0) | 7 | (50.0) | 0.34 | 4.00 | 0.35–45.38 | 7 | (46.7) | 4 | (100) | 0.10 | ||
RR (CR+R), no. of cases (%) | 5 | (100) | 9 | (64.3) | 0.26 | 10 | (66.7) | 4 | (100) | 0.53 | ||||
Eradication of Helicobacter pylori, no. of cases (%) | 7 | (41.2) | 36 | (33.6) | 0.59 | 1.38 | 0.49–3.93 | 33 | (37.9) | 10 | (27.0) | 0.24 | 1.65 | 0.71–3.84 |
Response to eradication of Helicobacter pylori
| ||||||||||||||
CR, no. of cases (%) | 4 | (57.1) | 16 | (44.4) | 0.69 | 1.67 | 0.33–8.55 | 15 | (45.5) | 5 | (50.0) | 1.00 | 0.83 | 0.20–3.44 |
Severe ITP, no. of cases (%) | 5 | (29.4) | 19 | (17.4) | 0.32 | 1.97 | 0.62–6.26 | 19 | (21.6) | 5 | (13.2) | 0.33 | 1.82 | 0.62–5.29 |
Refractory ITP, no. of cases (%) | 0 | (0) | 10 | (9.2) | 0.36 | 9 | (10.2) | 1 | (2.6) | 0.28 | 4.22 | 0.52–34.51 | ||
Corticosteroid-dependent, no. of cases (%) | 5 | (33.3) | 32 | (30.2) | 0.77 | 1.16 | 0.37–3.66 | 28 | (33.3) | 9 | (24.3) | 0.39 | 1.56 | 0.65–3.74 |