Table 2.
Association between anti-AGE and anti-MAA antibodies and HLA-SE and HLA-DRB1*03 presence in RA and HLA-DRB1*03 presence in non-RA patients from the Leiden EAC cohort
| Part I | RA n=648 | ||||||||
| HLA-SE− | HLA-SE+ | Total | OR | 95% CI | P value | OR | 95% CI | P value | |
| Healthy controls | 674 (55.7) | 537 (44.3) | 1211 | 1 (ref) | |||||
| Anti-AGE− | 139 (38.7%) | 220 (61.3%) | 359 | 1.99 | (1.56 to 2.53) | <0.001 | 1 (ref) | ||
| Anti-AGE+ | 99 (34.3%) | 190 (65.7%) | 289 | 2.41 | (1.84 to 3.15) | <0.001 | 1.21 | (0.88 to 1.67) | 0.24 |
| Anti-MAA− | 130 (37.2%) | 219 (62.8%) | 349 | 2.11 | (1.66 to 2.70) | <0.001 | 1 (ref) | ||
| Anti-MAA+ | 108 (36.1%) | 191 (63.9%) | 299 | 2.22 | (1.71 to 2.88) | <0.001 | 1.04 | (0.76 to 1.45) | 0.77 |
| HLA-DRB1*03− | HLA-DRB1*03+ | Total | OR | 95% CI | P value | OR | 95% CI | P value | |
| Healthy controls | 941 (77.7%) | 270 (22.3%) | 1211 | 1 (ref) | – | – | – | – | – |
| Anti-AGE− | 271 (75.5%) | 88 (24.5%) | 359 | 1.13 | (0.86 to 1.49) | 0.38 | 1 (Ref) | – | – |
| Anti-AGE+ | 211 (73.0%) | 78 (27.0%) | 289 | 1.29 | (0.96 to 1.73) | 0.09 | 1.14 | (0.80 to 1.62) | 0.47 |
| Anti-MAA− | 266 (76.2%) | 83 (23.8%) | 349 | 1.09 | (0.82 to 1.44) | 0.56 | 1 (ref) | – | – |
| Anti-MAA+ | 216 (72.2%) | 83 (27.8%) | 299 | 1.34 | (1.01 to 1.78) | 0.05 | 1.23 | (0.87 to 1.75) | 0.25 |
| non-RA n=246* | |||||||||
| HLA-DRB1*03− | HLA-DRB1*03+ | Total | OR | 95% CI | P value | OR | 95% CI | P value | |
| Healthy controls | 941 (77.7%) | 270 (22.3%) | 1211 | 1 (ref) | – | – | – | – | – |
| Anti-AGE− | 99 (76.7%) | 30 (23.3%) | 129 | 1.06 | (0.69 to 1.62) | 0.80 | 1 (Ref) | – | – |
| Anti-AGE+ | 70 (59.8%) | 47 (40.2%) | 117 | 2.34 | (1.58 to 3.47) | <0.001 | 2.22 | (1.28 to 3.84) | 0.01 |
| Anti-MAA− | 97 (72.4%) | 37 (27.6%) | 134 | 1.33 | (0.89 to 1.99) | 0.17 | 1 (ref) | – | – |
| Anti-MAA+ | 72 (64.3%) | 40 (35.7%) | 112 | 1.94 | (1.29 to 2.92) | 0.002 | 1.46 | (0.85 to 2.50) | 0.17 |
| Part II | anti-CCP2-negative RA n=301† | ||||||||
| HLA-DRB1*03− | HLA-DRB1*03+ | Total | OR | 95% CI | P value | OR | 95% CI | P value | |
| Healthy controls | 941 (77.7%) | 270 (22.3%) | 1211 | 1 (ref) | – | ||||
| Anti-AGE−Anti-CarP− | 125 (72.3%) | 48 (27.7%) | 173 | 1.34 | (0.93 to 1.92) | 0.11 | 1 (ref) | – | – |
| Anti-AGE+Anti-CarP− | 60 (63.8%) | 34 (36.2%) | 94 | 1.98 | (1.27 to 3.07) | 0.003 | 1.48 | (0.86 to 2.52) | 0.16 |
| Anti-AGE−Anti-CarP+ | 6 (50.0%) | 6 (50.0%) | 12 | 3.49 | (1.11 to 10.89) | 0.03 | 2.60 | (0.80 to 8.47) | 0.11 |
| Anti-AGE+Anti-CarP+ | 14 (50.0%) | 14 (50.0%) | 28 | 3.49 | (1.64 to 7.40) | 0.001 | 2.60 | (1.16 to 5.87) | 0.02 |
| anti-CCP2-negative RA n=307‡ | |||||||||
| HLA-DRB1*03− | HLA-DRB1*03+ | Total | OR | 95% CI | P value | OR | 95% CI | P value | |
| Healthy controls | 941 (77.7%) | 270 (22.3%) | 1211 | 1 (ref) | – | ||||
| Anti-MAA−Anti-CarP− | 135 (73.8%) | 48 (26.2%) | 183 | 1.24 | (0.87 to 1.77) | 0.24 | 1 (ref) | – | – |
| Anti-MAA+Anti-CarP− | 50 (59.5%) | 34 (40.5%) | 84 | 2.37 | (1.50 to 3.74) | <0.001 | 1.91 | (1.11 to 3.30) | 0.02 |
| Anti-MAA−Anti-CarP+ | 6 (42.9%) | 8 (57.1%) | 14 | 4.65 | (1.60 to 13.51) | 0.01 | 3.75 | (1.24 to 11.36) | 0.02 |
| Anti-MAA+Anti-CarP+ | 14 (53.8%) | 12 (46.2%) | 26 | 2.99 | (1.37 to 6.54) | 0.01 | 2.41 | (1.04 to 5.58) | 0.04 |
| Part III | SE-negative RA n=271† § | ||||||||
| HLA-DRB1*03− | HLA-DRB1*03+ | Total | OR | 95% CI | P value | OR | 95% CI | P value | |
| Healthy controls | 941 (77.7%) | 270 (22.3%) | 1211 | 1 (ref) | – | – | |||
| Anti-AGE−Anti-CarP− | 110 (82.7) | 23 (17.3) | 133 | 0.73 | 0.46 to 1.17) | 0.29 | 1 (ref) | – | – |
| Anti-AGE+Anti-CarP− | 36 (58.1) | 26 (41.9) | 62 | 2.52 | (1.49 to 4.24) | <0.001 | 3.45 | (1.76 to 6.79) | <0.001 |
| Anti-AGE−Anti-CarP+ | 23 (59.0) | 16 (41.0) | 39 | 2.42 | (1.26 to 4.66) | 0.008 | 3.33 | (1.52 to 7.26) | 0.003 |
| Anti-AGE+Anti-CarP+ | 23 (62.2) | 14 (37.8) | 37 | 2.12 | (1.08 to 4.18) | 0.03 | 2.91 | (1.31 to 6.49) | 0.009 |
| SE-negative RA n=269¶ | |||||||||
| HLA-DRB1*03− | HLA-DRB1*03+ | Total | OR | 95% CI | P value | OR | 95% CI | P value | |
| Healthy controls | 941 (77.7%) | 270 (22.3%) | 1211 | 1 (ref) | – | – | |||
| Anti-MAA−Anti-CarP− | 114 (85.7%) | 19 (14.3) | 133 | 0.58 | (0.35 to 0.96) | 0.04 | 1 (ref) | – | – |
| Anti-MAA+Anti-CarP− | 35 (58.3%) | 25 (41.7) | 60 | 2.49 | (1.46 to 4.23) | <0.001 | 4.29 | (2.11 to 8.69) | <0.001 |
| Anti-MAA−Anti-CarP+ | 15 (51.7) | 14 (48.3) | 29 | 3.25 | (1.56 to 6.82) | 0.002 | 5.60 | (2.33 to 13.44) | <0.001 |
| Anti-MAA+Anti-CarP+ | 31 (66.0) | 16 (34.0) | 47 | 1.80 | (0.97 to 3.34) | 0.06 | 3.10 | (1.43 to 6.72) | 0.004 |
Statistically significant difference between patient group and healthy controls (p≤0.05).
*HLA-DRB1*03 data were present from 246 of 538 patients without RA.
†HLA-DRB1*03 as well as anti-CarP and anti-AGE data was present from 301 of 648 patients with RA.
‡HLA-DRB1*03 as well as anti-CarP and anti-MAA data was present from 307 of 648 patients with RA.
§HLA-SE as well as anti-CarP and anti-AGE data was present from 271 of 648 patients with RA.
¶HLA-SE as well as anti-CarP and anti-MAA data was present from 269 of 648 patients with RA.
AGE, advanced glycation end-products; CarP, carbamylated protein; CCP2, citrullinated cyclic peptide 2; HLA-SE, human leucocyte antigen shared epitope; MAA, malondialdehyde acetaldehyde adducts; RA, rheumatoid arthritis.