Background
Methods
Design, setting, patients, and measurements
Genotyping methods
MEFV gene analysis
Statistical analysis
Results
Demographic findings of enrolled patients with AOSD
Variable | Value |
---|---|
Number | 87 |
Female, n (%) | 69 (79.3) |
Age at onset (years) | 49.3 ± 19.9 |
Ferritin (ng/mL) | 11251.2 ± 16997.9 |
CRP (mg/dL) | 12.4 ± 8.2 |
ESR (mm(1 h)) | 71.1 ± 30.1 |
Liver dysfunction, n (%) | 68 (78.1) |
MAS, n (%) | 23 (26.4) |
Initial dose of PSL (mg/day) | 41.8 ± 12.2 |
Steroid pulse, n (%) | 55 (63.2) |
Immunosuppressant, n (%) | 51 (58.6) |
Biologics, n (%) | 26 (29.8) |
Polycyclic systemic type, n (%) | 56 (64.3) |
Monocyclic systemic type, n (%) | 19 (21.8) |
Chronic arthritis type, n (%) | 12 (13.7) |
Relapse, n (%) | 40 (45.9) |
Association of specific DRB1 alleles with AOSD
Cases (n = 96) | Controls (n = 1026) |
P
| OR |
Pc | 95% CI | |
---|---|---|---|---|---|---|
DRB1*01:01
| 9 (9.4) | 110 (10.7) | 0.8622 | 0.86 | NS | (0.42–1.76) |
DRB1*03:01
| 0 (0.0) | 3 (0.3) | 1.0000 | 1.52 | NS | (0.08–29.55) |
DRB1*04:01
| 0 (0.0) | 22 (2.1) | 0.2486 | 0.23 | NS | (0.01–3.84) |
DRB1*04:03
| 4 (4.2) | 47 (4.6) | 1.0000 | 0.91 | NS | (0.32–2.57) |
DRB1*04:04
| 0 (0.0) | 4 (0.4) | 1.0000 | 1.18 | NS | (0.06–22.03) |
DRB1*04:05
| 21 (21.9) | 243 (23.7) | 0.8014 | 0.90 | NS | (0.54–1.49) |
DRB1*04:06
| 2 (2.1) | 76 (7.4) | 0.0562 | 0.27 | NS | (0.06–1.10) |
DRB1*04:07
| 0 (0.0) | 15 (1.5) | 0.6313 | 0.34 | NS | (0.02–5.70) |
DRB1*04:10
| 4 (4.2) | 32 (3.1) | 0.5413 | 1.35 | NS | (0.47–3.90) |
DRB1*07:01
| 0 (0.0) | 9 (0.9) | 1.0000 | 0.55 | NS | (0.03–9.61) |
DRB1*08:02
| 13 (13.5) | 72 (7.0) | 0.0403 | 2.08 | NS | (1.10–3.90) |
DRB1*08:03
| 16 (16.7) | 153 (14.9) | 0.6544 | 1.14 | NS | (0.65–2.01) |
DRB1*08:09
| 0 (0.0) | 2 (0.2) | 1.0000 | 2.12 | NS | (0.10–44.55) |
DRB1*09:01
| 11 (11.5) | 280 (27.3) | 0.0004 | 0.34 | 0.0110 | (0.18–0.66) |
DRB1*10:01
| 0 (0.0) | 5 (0.5) | 1.0000 | 0.96 | NS | (0.05–17.54) |
DRB1*11:01
| 6 (6.3) | 41 (4.0) | 0.2837 | 1.60 | NS | (0.66–3.87) |
DRB1*12:01
| 16 (16.7) | 75 (7.3) | 0.0031 | 2.54 | 0.0896 | (1.41–4.56) |
DRB1*12:02
| 8 (8.3) | 37 (3.6) | 0.0488 | 2.43 | NS | (1.10–5.38) |
DRB1*13:01
| 2 (2.1) | 8 (0.8) | 0.2082 | 2.71 | NS | (0.57–12.93) |
DRB1*13:02
| 5 (5.2) | 163 (15.9) | 0.0040 | 0.29 | 0.1150 | (0.12–0.73) |
DRB1*14:03
| 7 (7.3) | 44 (4.3) | 0.1941 | 1.76 | NS | (0.77–4.01) |
DRB1*14:04
| 0 (0.0) | 4 (0.4) | 1.0000 | 1.18 | NS | (0.06–22.03) |
DRB1*14:05
| 6 (6.3) | 40 (3.9) | 0.2758 | 1.64 | NS | (0.68–3.98) |
DRB1*14:06
| 2 (2.1) | 29 (2.8) | 1.0000 | 0.73 | NS | (0.17–3.11) |
DRB1*14:07
| 0 (0.0) | 2 (0.2) | 1.0000 | 2.12 | NS | (0.10–44.55) |
DRB1*14:54
| 6 (6.3) | 58 (5.7) | 0.8168 | 1.11 | NS | (0.47–2.65) |
DRB1*15:01
| 31 (32.3) | 139 (13.5) | 8.60 × 10-6
| 3.04 | 0.0002 | (1.91–4.84) |
DRB1*15:02
| 18 (18.8) | 224 (21.8) | 0.5197 | 0.83 | NS | (0.48–1.41) |
DRB1*16:02
| 0 (0.0) | 18 (1.8) | 0.3919 | 0.28 | NS | (0.02–4.72) |
DR5(*11, *12) | 28 (29.2) | 151 (14.7) | 0.0006 | 2.39 | (1.49–3.83) |
Reduced DRB1*09:01 allele carrier frequencies in AOSD
Cases (n = 96) | Controls (n = 1026) |
P
| OR | 95% CI | |
---|---|---|---|---|---|
*15:01/any alleles | 31 (32.3) | 139 (13.5) | 8.60 × 10-6
| 3.04 | (1.91-4.84) |
*15:01/*09:01
| 1 (1.0) | 21 (2.0) | 1.0000 | 0.50 | |
*15:01/alleles other than *09:01
| 30 (31.3) | 118 (11.5) | 1.64 × 10-6
| 3.50 | (2.18-5.61) |
MEFV variant analysis
Mutations | Number of patients (percentage) (n = 87) |
---|---|
M694I/normal | 2 (2.3) |
G632S/E408Q | 1 (1.1) |
P369S/R408Q | 4 (4.6) |
E148Q/P369S | 1 (1.1) |
E148Q/E148Q/P369S/R408Q | 1 (1.1) |
L110P/E148Q/E148Q/P369S/R408Q | 1 (1.1) |
E148Q/P369S/R408Q | 2 (2.3) |
E148Q/R202Q | 1 (1.1) |
R202Q/normal | 3 (3.4) |
E148Q/normal | 19 (21.8) |
E148Q/E148Q | 2 (2.3) |
L110P/E148Q | 6 (6.9) |
L110P/E148Q//E148Q | 2 (2.3) |
L110P/E148Q//R202Q | 1 (1.1) |
L110P/L110P/E148Q//E148Q | 1 (1.1) |
E84K/normal | 1 (1.1) |
E84K/L110P/E148Q | 1 (1.1) |
Normal | 38 (43.7) |
AOSD with MEFV variants | AOSD without MEFV variants | Controls | AOSD with MEFV variants vs. controls | AOSD without MEFV variants vs. controls | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
(n = 49) | (n = 38) | (n = 1026) |
P
| OR |
Pc | 95% CI |
P
| OR |
Pc | 95% CI | |
DRB1*15:01
| 17 (34.7) | 13 (34.2) | 139 (13.5) | 0.0002 | 3.39 | 0.0068 | (1.83–6.27) | 0.0013 | 3.32 | 0.0388 | (1.66–6.64) |
DR5(DRB1*11, *12) | 16 (32.7) | 8 (21.1) | 151 (14.7) | 0.0019 | 2.81 | (1.51–5.23) | 0.2543 | 1.55 | (0.70–3.43) |
Association of specific DRB1 alleles and clinical manifestations of AOSD
DRB1*15:01 (+) |
DRB1*15:01 (-) |
P
|
DR5 (+) |
DR5 (-) |
P
| |
---|---|---|---|---|---|---|
Number | 29 | 58 | 23 | 64 | ||
Female, n (%) | 24 (82.7) | 45 (77.5) | 0.7789 | 20 (86.9) | 49 (77.4) | 0.2912 |
Age at onset (years) | 46.6 ± 20.3 | 50.6 ± 19.6 | 0.3980 | 50.6 ± 20.5 | 48.1 ± 19.7 | 0.7469 |
Ferritin (ng/mL) | 12818.5 ± 18292.9 | 10555.5 ± 16284.7 | 0.3657 | 12669.4 ± 16305.9 | 10802.9 ± 17224.9 | 0.3243 |
CRP (mg/dL) | 11.9 ± 8.2 | 12.7 ± 8.3 | 0.6802 | 12.0 ± 9.2 | 12.6 ± 7.9 | 0.5068 |
ESR (mm(1 h)) | 59.6 ± 25.3 | 75.4 ± 30.9 | 0.1289 | 67.4 ± 23.0 | 72.5 ± 32.5 | 0.9361 |
Liver dysfunction, n (%) | 24 (82.7) | 44 (75.8) | 0.4630 | 19 (82.6) | 49 (76.5) | 0.5472 |
MAS, n (%) | 10 (38.6) | 13 (22.4) | 0.2288 | 10 (43.4) | 13 (20.3) | 0.0307 |
Initial dose of PSL (mg/day) | 43.8 ± 13.0 | 41.5 ± 11.7 | 0.4379 | 46.1 ± 10.9 | 40.3 ± 12.4 | 0.1184 |
Steroid pulse, n (%) | 17 (58.6) | 38 (65.5) | 0.4987 | 19 (82.6) | 36 (56.2) | 0.0245 |
Immunosuppressant, n (%) | 18 (57.6) | 33 (56.8) | 0.6442 | 15 (65.2) | 36 (56.2) | 0.4539 |
Biologics, n (%) | 10 (38.6) | 16 (27.5) | 0.5077 | 6 (26.0) | 20 (31.2) | 0.6427 |
Polycyclic systemic type, n (%) | 20 (68.9) | 36 (62.0) | 0.5266 | 18 (78.2) | 38 (59.3) | 0.1048 |
Monocyclic systemic type, n (%) | 8 (27.5) | 13 (22.4) | 0.5951 | 4 (17.3) | 17 (26.5) | 0.3780 |
Chronic arthritis type, n (%) | 4 (13.7) | 8 (13.7) | 1.0000 | 2 (8.6) | 10 (15.6) | 0.4085 |
Relapse, n (%) | 14 (48.2) | 26 (44.8) | 0.7619 | 11 (47.8) | 29 (45.3) | 0.8357 |