Background
Methods
Population sample
SLE survey questionnaire | Positive answers | |
---|---|---|
% of Patients | % of Relatives | |
1. Have you ever had painful swollen joints for more than three months? | 65.0 | 13.6 |
2. Do your fingers ever change color, become numb or uncomfortable in the cold? | 63.3 | 26.4 |
3. Have you ever had mouth ulcers for more than two weeks? | 40.0 | 18.6 |
4. Have you ever been told that you have low blood counts (anemia, low white cell count or low platelet count)? | 71.7 | 15.0 |
5. Have you ever had an obvious or prominent rash on your cheeks for more than a month? | 71.7 | 9.3 |
6. Do you develop a distinct rash in the sun (not just sunburn)? | 66.7 | 10.0 |
7. Has it ever been painful to take a deep breath for more than just a few days (pleurisy)? | 33.3 | 4.3 |
8. Have you ever been told that you have protein in the urine? | 26.7 | 0.0 |
9. Do you find a lot of hair on your pillow on waking? | 43.0 | 10.7 |
10.Have you ever had a seizure, convulsion or fit? | 3.0 | 0.7 |
Cell surface staining and flow cytometry
Anti-dsDNA autoantibody measurement by quantitative ELISA
Genotyping
mRNA isolation and quantification
Statistical analysis
Results
Lower frequency of CD4+CD25+ and CD4+CD25+CD45RO+ cells in SLE patients
SLE patients display higher frequency of CD4+FOXP3+ cells which are mainly CD25-
CD4+CD25+CD45RO+ T cell frequency is negatively correlated with SLE-associated phenotypes
Variation of CD4+CD25+CD45RO+ T cell frequency with the development and remission of SLE-related symptoms
Peripheral CD4+CD25+CD45RO+ T cell frequency is highly heritable
Lower frequency of CD4+CD25+CD45RO+ T cells is associated with specific CTLA4 and TGFβ gene variants
CTLA4 rs 231775 genotypes | N (%) | Median % CD4+CD25+CD45RO+Cells | Kruskall-Wallis Test |
P
|
---|---|---|---|---|
A/A | 39(13.22) | 3.30 | ||
A/G | 115(38.98) | 2.98 | 1.24 | 0.537 |
G/G | 141 (47.80) | 2.80 | ||
CTLA4
3'UTR microssatelite genotypes
| ||||
88/88 | 100 (38.02) | 3.10 | ||
88/104 | 9 (3.42) | 2.66 | ||
88/106 | 26 (10.27) | 2.58 | 40.57 | 0.0009 |
104/104 | 3 (1.14) | 2.54 | ||
106/106 | 5 (1.90) | 4.01 | ||
Rare | 119 (45.25) | 2.81 | ||
TGFβ
rs18000469 genotypes
| ||||
C/C | 37(12.38) | 3.55 | ||
C/T | 122 (40.80) | 2.94 | 0.427 | 0.808 |
T/T | 140 (46.82) | 3.27 | ||
TGFβ
rs18000471 genotypes
| ||||
G/G | 255 (86.44) | 3.29 | 8.10 | 0.004 |
G/C | 41 (13.56) | 2.10 | ||
FOXP3
FOX0 microssatelite genotypes
| ||||
1/4 | 3 (1.42) | 2.54 | ||
1/5 | 2 (0.95) | 2.65 | ||
4/4 | 68 (32.23) | 3.15 | ||
4/5 | 76 (36.02) | 2.77 | ||
4/6 | 21 (9.96) | 2.58 | 9.06 | 0.911 |
4/7 | 3 (1.42) | 5.22 | ||
5/5 | 26 (12.32) | 2.59 | ||
5/6 | 6 (2.84) | 2.08 | ||
Rare | 6 (2.84) | 3.22 | ||
FOXP3
FOX5 microssatelite genotypes
| ||||
1/3 | 3 (1.59) | 2.87 | ||
1/4 | 4 (2.10) | 3.79 | ||
3/3 | 77 (40.74) | 3.10 | ||
3/8 | 5 (2.65) | 2.54 | ||
3/10 | 10 (5.29) | 3.17 | ||
3/12 | 13 (6.88) | 2.99 | ||
3/13 | 11 (5.82) | 2.36 | ||
3/14 | 43 (22.75) | 2.51 | 9.06 | 0.911 |
3/15 | 3 (1.59) | 3.16 | ||
3/16 | 8 (4.23) | 3.54 | ||
3/18 | 3 (1.59) | 2.74 | ||
3/19 | 2 (1.06) | 3.50 | ||
7/13 | 2 (1.06) | 3.76 | ||
8/14 | 2 (1.06) | 2.00 | ||
Rare | 3 (1.59) | 3.19 | ||
IL2
rs20699762 genotypes
| ||||
G/G | 137 (47.90) | 3.55 | ||
G/T | 121 (42.31) | 3.81 | 1.906 | 0.386 |
T/T | 28 (9.79) | 3.33 | ||
IL2
rs3087209 genotypes
| ||||
G/G | 28 (9.82) | 3.04 | ||
G/T | 101 (35.44) | 3.81 | 0.944 | 0.624 |
T/T | 156 (54.74) | 3.16 | ||
CD25
D10S189 genotypes
| ||||
1/1 | 7 (2.54) | 2.58 | ||
1/2 | 57 (20.73) | 3.08 | ||
1/3 | 1 (0.36) | 4.06 | ||
1/4 | 28 (10.18) | 2.92 | ||
1/5 | 21 (7.64) | 3.37 | ||
2/2 | 35 (12.73) | 3.65 | 14.932 | 0.312 |
2/4 | 62 (22.54) | 3.51 | ||
2/5 | 32 (11.64) | 3.25 | ||
3/4 | 3 (1.09) | 2.51 | ||
4/4 | 11 (4.00) | 2.68 | ||
4/5 | 16 (5.82) | 2.55 | ||
5/5 | 2 (0.73) | 5.77 | ||
CD25
rs2274037 genotypes
| ||||
A/A | 140 (83.83) | 4.29 | 0.008 | 0.931 |
A/G | 27 (16.17) | 4.23 | ||
CD25
rs1570538 genotypes
| ||||
C/C | 50 (25.25) | 4.43 | ||
C/T | 110 (55.56) | 3.67 | 2.110 | 0.348 |
T/T | 38 (19.19) | 3.51 |
Patients | Controls | ||||
---|---|---|---|---|---|
rs 12843496 allele
|
Number of alleles (%)
|
Number of alleles (%)
| χ2 |
P
|
OR (95%CI)
|
G | 293 (96.7) | 233 (100) | - | ||
A | 10 (3.3) | 0 (0.0) | 6.137 | 0.013 | - |
Total
| 303 (100) | 233 (100) | |||
FOX0 allele
| |||||
1 | 7 (2.3) | 4 (1.7) | 0.04 | 0.84 | 1.38 (0.40–4.78) |
4 | 189 (61.6) | 121 (50.2) | 6.63 | 0.01 | 1.59 (1.13–2.24) |
5 | 97 (31.6) | 93 (38.6) | 2.61 | 0.10 | 0.74 (0.52–1.05) |
6 | 11 (3.6) | 19 (7.9) | 4.03 | 0.04 | 0.24 (0.11–0.52) |
Rare | 3 (0.9) | 4 (1.6) | 0.10 | 0.75 | 0.81 (0.18–3.63) |
Total
| 307 (100) | 241 (100) | 10.3 | 0.036 | |
FOX5 allele
| |||||
3 | 188 (63.7) | 137 (57.9) | 1.65 | 0.20 | 1.28 (0.90–1.82) |
8 | 6 (2.0) | 6 (2.6) | 0.01 | 0.92 | 0.80 (0.25–2.49) |
10 | 13 (4.4) | 4 (1.7) | 2.27 | 0.13 | 2.66 (0.86–8.28) |
12 | 17 (5.8) | 21 (8.9) | 1.53 | 0.22 | 0.99 (0.54–1.80) |
13 | 7 (2.4) | 7 (3.0) | 0.03 | 0.87 | 0.79 (0.27–2.29) |
14 | 46 (15.6) | 38 (16.2) | <0.01 | 0.95 | 0.96 (0.60–1.53) |
15 | 3 (1.0) | 5 (2.1) | 0.43 | 0.51 | 0.47 (0.11–2.00) |
16 | 7 (2.4) | 9 (3.8) | 0.52 | 0.47 | 0.61 (0.22–1.66) |
18 | 0 (0.0) | 5 (2.1) | 4.26 | 0.04 | - |
Rare | 8 (2.7) | 4 (1.7) | 0.23 | 0.63 | 1.61 (0.48–5.41) |
Total
| 295 (100) | 235 (100) | 14.77 | 0.10 | |
rs 12843496 genotypes
| |||||
GG | 136 (93.8) | 77 (100) | 3.51 | 0.06 | - |
GA | 8 (5.5) | 0 (0.0) | 2.96 | 0.09 | - |
AA | 1 (0.7) | 0 (0.0) | 0.11 | 0.74 | - |
Total
| 145 (100) | 77 (100) | 4.98 | 0.08 | |
FOX0 genotypes
| |||||
4/4 | 50 (33.8) | 22 (25.3) | 1.48 | 0.22 | 1.50 (0.83–2.72) |
4/5 | 63 (42.6) | 35 (40.2) | 0.05 | 0.83 | 1.10 (0.64–1.88) |
4/6 | 9 (6.1) | 6 (6.9) | <0.01 | 0.98 | 0.87 (0.30–2.55) |
5/5 | 12 (8.1) | 13 (14.9) | 2.02 | 0.16 | 0.50 (0.21–1.16) |
Rare | 14 (9.4) | 11 (12.7) | 0.30 | 0.50 | 0.72 (0.31–1.67) |
Total
| 148 (100) | 87 (100) | 4.35 | 0.36 | |
FOX5 genotypes
| |||||
3/3 | 59 (33.8) | 28 (33.3) | 0.72 | 0.40 | 1.33 (0.76–2.32) |
3/12 | 8 (5.4) | 5 (6.0) | 0.02 | 0.90 | 0.90 (0.29–2.85) |
3/13 | 6 (4.1) | 4 (4.8) | 0.01 | 0.94 | 0.85 (0.23–3.08) |
3/14 | 32 (21.6) | 16 (19.1) | 0.09 | 0.77 | 1.17 (0.60–2.29) |
3/15 | 2 (1.4) | 3 (3.6) | 0.38 | 0.54 | 0.38 (0.06–2.32) |
3/16 | 5 (3.4) | 3 (3.6) | 0.09 | 0.77 | 0.94 (0.22–4.05) |
3/18 | 0 (0.0) | 5 (6.0) | 6.4 | 0.01 | - |
14/14 | 4 (2.7) | 3 (3.6) | <0.01 | 0.98 | 0.75 (0.16–3.43) |
Rare | 32 (21.6) | 17 (20.2) | 0.01 | 0.94 | 1.09 (0.56–2.10) |
Total
| 148 (100) | 84 (100) | 11.1 | 0.10 |