Introduction and concepts of pathogenesis
Age | 55 ± 12 |
Male gender | 134 (47) |
Family history of psoriasis (n = 280) | 175 (63) |
Family history of PsA (n = 280) | 45 (16) |
Age of onset of psoriasis | 28 ± 14 |
Psoriasis duration (years) | 27 ± 14 |
Age of onset of PsA | 35 ± 13 |
PsA duration (years) | 19 ± 9 |
Years between psoriasis and PsA | 6 (0 to 14) |
Psoriasis before PsA | 184 (65) |
PsA before psoriasis | 45 (16) |
Psoriasis and PsA at same time | 52 (18) |
Nail disease | 244 (79) |
Pitting | 96 (34) |
Onycholysis | 155 (55) |
Peripheral arthritis | 280 (99) |
Polyarthritis | 258 (91) |
Oligoarthritis | 21 (8) |
Deformed joint count, if deformity | 6 (4 to 12) |
Enthesitisa
| 97 (34) |
Dactylitisa
| 150 (53) |
Sacroiliitisa
| 71 (25) |
Asymmetrica
| 51 (18) |
Symmetrica
| 18 (6) |
Joint deformitya
| 183 (65) |
Joint fusiona
| 83 (29) |
Erosionsa (n = 281) | 123 (44) |
Osteolysisa (n = 281) | 41 (15) |
Current PASI | 1.2 (0.3 to 2.8) |
Max PASI | 3.8 (1.8 to 9.2) |
Plaque psoriasis only | 224 (79) |
Psoriasis, nonplaque | 59 (21) |
Uveitis | 9 (3) |
Total on TNFi | 176 (62) |
Psoriasis requiring TNFi | 32 (11) |
PsA requiring TNFi | 171 (60) |
Number of TNFi, if on TNFi | 1 (1 to 2; range 1 to 4) |
Number of DMARDs | 1 (1 to 2; range 0 to 5) |
Psoriatic arthritis is an autoimmune disease
Psoriatic arthritis is an entheseal-based disease
Review: genetics of psoriatic arthritis
Background findings
New data concerning psoriatic arthritis genetics
HLA allele
|
PsA (%),
n
= 359
|
PsA versus control
|
PsO (%),
n
= 214
|
PsO versus control
|
Control (%),
n
= 1,000
|
PsA versus PsO
|
---|---|---|---|---|---|---|
B*57:01
| 18.4 | 2.5 (1.6 to 3.8) | 31.3 | 5.71 (3.9 to 8.3) | 7.4 | 0.30 (0.17 to 0.53) |
C*06:02
| 28.7 | 1.8 (1.3 to 2.5) | 57.5 | 6.61 (4.18 to 9.1) | 19.3 | 0.26 (0.16 to 0.42) |
HLA allele
|
PsA (%),
n
= 359
|
PsA versus control
|
PsO (%),
n
= 214
|
PsO versus control
|
Control (%),
n
= 1,000
|
PsA versus PsO
|
---|---|---|---|---|---|---|
B*27:05
| 15.6 | 2.6 (1.7 to 4.2) | 4.7 |
P = 0.23 | 5.5 | 3.77 (1.9 to 7.6) |
B*39:01
| 6.4 | 3.5 (1.6 to 7.6) | 1.4 |
P = 1 | 1.2 | 2.86 (1.1 to 7.6) |
B*08:01
| 37.3 | 1.6 (1.2 to 2.0) | 24.8 | 0.43 (0.25 to 0.76) | 30.1 | 1.81 (1.6 to 6.5) |
B*44:02
| 14.8 | 0.53 (0.36 to 0.80) | 22.4 |
P = 0.7 | 24.6 | 0.60 (0.29 to 0.87) |
HLA-B molecule
|
P2 pocket amino acid position
|
P2 amino acid binding preference
|
Allele risk estimate
a
| |
---|---|---|---|---|
45
|
67
| |||
B*27:05:02
| Glu | Cys | Arg | 3.18 (2.14 to 4.71) |
B*39:01:01
| Glu | Cys | Arg | 3.74 (1.99 to 7.01) |
B*44:02:01
| Lys | Ser | Glu | 0.53 (0.38 to 0.74) |
B*44:03:01
| Lys | Ser | Glu | 0.47 (0.24 to 0.92) |
Different susceptibility genes imply different disease mechanisms, and possibly a different clinical course and therapeutic responses
Genotype influences the duration between cutaneous and musculoskeletal involvement
Genetic influence on whether sacroiliitis is symmetrical or asymmetrical
Marker
|
Sacroiliitis
|
Symmetrical sacroiliitis
|
Asymmetrical sacroiliitis
|
---|---|---|---|
B*08:01
| 50.70% | 16.70% | 62.70% |
P value | 0.006 | 0.066 | <0.000 |
OR (95% CI) | 2.15 (1.06 to 1.77) | 0.323 (0.91 to 1.143) | 3.8 (1.9 to 7) |
B*27:05
| 23.20% | 61.10% | 9.80% |
P value | 0.059 | <0.000 | 0.185 |
OR (95% CI) | 1.92 (0.97 to 3.79) | 10.63 (3.86 to 29.3) | 0.52 (0.19 to 1.39) |
C*01:02
| 18.6% | 36.80% | 11.80% |
P value | 0.027 | <0.000 | 0.9 |
OR (95% CI) | 2.32 (1.08 to 5.00) | 5.57 (2.02 to 15.5) | 1.06 (0.41 to 2.76) |
C*02:02
| 10% | 26% | 4% |
P value | 0.42 | 0.002 | 0.26 |
OR (95% CI) | 1.47 (0.57 to 3.76) | 5.19 (1.67 to 16.1) | 0.43 (0.09 to 1.9) |
C*07:01
| 48.60% | 15.8% | 60.80% |
P value | 0.119 | 0.022 | 0.001 |
OR (95% CI) | 1.53 (0.89 to 2.62) | 0.25 (0.07 to 0.89) | 1.73 (1.47 to 5.1) |
B*08-C*07
| 47% | 16% | 59% |
P value | 0.026 | 0.057 | <0.000 |
OR (95% CI) | 1.86 (1.07 to 3.23) | 0.31 (0.089 to 1.1) | 3.18 (1.7 to 5.92) |
B*27-C*01
| 14.30% | 31.60% | 7.80% |
P value | 0.064 | 0.001 | 0.78 |
OR (95% CI) | 2.2 (0.94 to 5.15) | 5.9 (2.0 to 17) | 0.85 (0.28 to 2.61) |
B*27-C*02
| 8.6% | 26.3% | 2.00% |
P value | 0.474 | <0.000 | 0.134 |
OR (95% CI) | 1.44 (0.53 to 3.95) | 6.4 (2.0 to 20) | 2.4 (0.03 to 1.8) |
Marker
|
Enthesitis
|
---|---|
B*27:05
| 28.10% |
P value | <0.000 |
OR (95% CI) | 3.65 (1.89 to 7.06) |
C*01:02
| 21.60% |
P value | <0.000 |
OR (95% CI) | 4.39 (2.02 to 9.57) |
C*02:02
| 10% |
P value | 0.25 |
OR (95% CI) | 1.67 (0.69 to 4.01) |
B*27-C*01
| 17.50% |
P value | <0.000 |
OR (95% CI) | 4.73 (1.96 to 11.41) |
B*27-C*02
| 9.30% |
P value | 0.213 |
OR (95% CI) | 1.80 (0.71 to 4.59) |
Human leukocyte antigen associations of enthesitis
Synovial-based phenotypes are associated with B*08:01
Dactylitis exhibits a dual association with B*27:05 and B*08:01
HLA allele or haplotype
|
Frequency (%) of HLA
|
Odds ratio (95% CI)
|
P
value (two-sided)
| |
---|---|---|---|---|
With trait
|
Without trait
| |||
B*27:05:02
| 21.3 | 9.8 | 2.5 (1.2 to 5.0) | 0.009 |
B*27:05:02-C*01:02:01
| 12.0 | 5.3 | 2.5 (1.0 to 6.1) | 0.05 |
B*27:05:02-C*02:02:02
| 8.7 | 4.5 | 2.0 (0.7 to 5.4) | 0.2 |
B*08:01:01
| 42.7 | 30.3 | 1.7 (1.1 to 2.8) | 0.03 |
B*08:01:01-C*07:01:01
| 42.0 | 29.3 | 1.8 (1.1 to 2.9) | 0.03 |
C*06:02:01
| 25.3 | 33.8 | 0.7 (0.4 to 1.1) | 0.1 |
B*44:02:01
| 9.3 | 22.0 | 0.37 (0.2 to 0.7) | 0.003 |
B*44:02:01-C*05:01:01
| 8.7 | 18.0 | 0.43 (0.2 to 0.89) | 0.02 |
B*44:03:01
| 6.0 | 15.2 | 0.36 (0.2 to 0.8) | 0.012 |
B*44:03:01-C*16:01:01
| 3.3 | 9.8 | 0.3 (0.1 to 0.9) | 0.03 |