Background
Methods
Patients and sera
Biomarker immunoassay
Statistical analysis
Results
Characteristics of collagen disease patients with AoDILD
Biomarker immunoassay
Biomarker (pg/ml) | Stable | AoDILD |
P
| ||
---|---|---|---|---|---|
TIMP-1 | 207843 | (57972) | 285600 | (98476) | 0.015 |
TIMP-2 | 121481 | (22995) | 101922 | (18568) | 0.006 |
TIMP-3 | 15662 | (11925) | 15653 | (7974) | 0.196 |
TIMP-4 | 2908 | (941) | 2874 | (837) | 0.906 |
MMP-3 | 854165 | (668239) | 499442 | (312919) | 0.010 |
MMP-9 | 2615399 | (1577133) | 2837226 | (1619793) | 0.563 |
TGF-β1 | 57391 | (12908) | 52821 | (16415) | 0.101 |
TGF-β2 | 2475 | (889) | 2201 | (997) | 0.101 |
TGF-β3 | 0 | (0) | 0 | (0) | 1.000 |
Leptin | 6424 | (6663) | 6275 | (8249) | 0.670 |
Osteopontin | 14603 | (12657) | 30216 | (33636) | 0.012 |
Insulin | 633 | (475) | 589 | (330) | 0.961 |
EGF | 131 | (124) | 130 | (189) | 0.355 |
Eotaxin2 | 4497 | (3166) | 4223 | (5065) | 0.018 |
Eotaxin3 | 44 | (71) | 37 | (52) | 0.625 |
IL-17 F | 125 | (340) | 168 | (519) | 0.761 |
IL-1α | 61 | (248) | 137 | (607) | 1.000 |
IL-1RA | 156 | (330) | 401 | (490) | 0.049 |
IL-2 | 41 | (121) | 77 | (246) | 0.427 |
IL-2Rα | 3623 | (2134) | 7469 | (6483) | 0.001 |
IL-6 | 103 | (234) | 363 | (794) | 0.035 |
Fas | 2237 | (9967) | 3450 | (13337) | 0.715 |
FasL | 68 | (63) | 74 | (74) | 0.763 |
TNFα | 841 | (1953) | 1052 | (2676) | 0.821 |
MMP-1 | 69662 | (86194) | 75510 | (58379) | 0.016 |
MMP-12 | 4992 | (14919) | 7406 | (23641) | 0.500 |
MMP-7 | 5874 | (5153) | 7871 | (11084) | 0.627 |
MMP-13 | 37860 | (74534) | 52019 | (111830) | 0.754 |
MMP-8 | 25817 | (17712) | 48700 | (54791) | 0.144 |
LIF | 57 | (150) | 121 | (353) | 0.441 |
MIF | 17352 | (34236) | 23178 | (29813) | 0.136 |
MMP-3/MMP-1 | 22.04 | (18.56) | 15.00 | (19.61) | 0.0208 |
Serum biomarker profile of the RA patients with AoDILD
RA patients (n = 18) | |||
---|---|---|---|
Stable | AoDILD |
P
| |
White Blood Cell count(X1000/ml) | 10.5 (3.8) | 12.1 (3.4) | 0.1578 |
Red Blood Cell count(X106/ml) | 4.2 (0.5) | 4.1 (0.6) | 0.8506 |
Hemoglobin(g/dl) | 12.6 (2.0) | 12.3 (1.8) | 0.6378 |
Hematocrit(%) | 39.4 (5.5) | 37.4 (5.3) | 0.4703 |
Platelet(X1000/ml) | 304.1 (121.2) | 285.9 (108.4) | 0.7064 |
Albumin(g/dl) | 3.9 (0.4) | 3.2 (0.6) | 0.0052 |
Aspartate Aminotransferase(IU/l) | 32.6 (39.8) | 38.6 (27.2) | 0.1167 |
Alanine Aminotransferase(IU/l) | 28.0 (36.3) | 26.4 (28.8) | 0.8068 |
Lactate Dehydrogenase(IU/l) | 224.7 (39.1) | 371.8 (143.4) | 0.0052 |
Alkaline Phosphatase(IU/l) | 275.4 (129.1) | 260.4 (93.3) | 0.9721 |
γ-glutamyltransferase(IU/l) | 33.5 (25.4) | 110.9 (309.5) | 0.1361 |
Creatinine(mg/dl) | 0.6 (0.1) | 0.7 (0.2) | 0.3627 |
Blood Urea Nitrogen(mg/dl) | 14.2 (2.8) | 17.3 (4.6) | 0.1005 |
C-reactive protein(mg/dl) | 3.6 (3.6) | 11.1 (9.3) | 0.1094 |
KL-6(IU/ml) | 447.9 (244.3) | 829.2 (473.8) | 0.0052 |
Surfactant Protein-D (SP-D)(U/ml) | 74.1 (51.1) | 169.3 (148.0) | 0.0157 |
TIMP-1(pg/ml) | 196945 (49413) | 302152 (102113) | 0.0071 |
TIMP-2(pg/ml) | 117585 (23704) | 99258 (16673) | 0.0231 |
MMP-3(pg/ml) | 910356 (732400) | 451701 (312564) | 0.0057 |
Osteopontin(pg/ml) | 17095 (13228) | 36200 (35682) | 0.0198 |
Eotaxin2(pg/ml) | 4482 (3387) | 3308 (4017) | 0.0108 |
IL-1RA(pg/ml) | 187 (365) | 401 (359) | 0.0759 |
IL-2Rα(pg/ml) | 3842 (2128) | 8624 (6810) | 0.0025 |
IL-6(pg/ml) | 123 (260) | 383 (852) | 0.1119 |
MMP-1(pg/ml) | 81755 (93582) | 87509 (60314) | 0.0582 |
MMP-8(pg/ml) | 28379 (17114) | 55764 (59399) | 0.1841 |
MMP-3/MMP-1 | 20.66 (20.57) | 12.83 (20.91) | 0.0249 |
Serum biomarker profile of the patients with AE-ILD or DI-ILD
AE-ILD (n = 9) | DI-ILD (n = 14) | |||||
---|---|---|---|---|---|---|
Stable | AoDILD |
P
| Stable | AoDILD |
P
| |
White Blood Cell count (X1000/ml) | 10.9 (2.7) | 11.8 (2.6) | 0.2135 | 10.3 (4.0) | 12.1 (3.8) | 0.2604 |
Red Blood Cell count (X106/ml) | 4.2 (0.9) | 4.4 (0.7) | 0.9528 | 4.2 (0.5) | 4.1 (0.6) | 0.5536 |
Hemoglobin (g/dl) | 13.4 (1.2) | 12.7 (2.5) | 0.2936 | 12.6 (2.3) | 12.2 (1.9) | 0.5147 |
Hematocrit (%) | 42.1 (3.1) | 38.9 (6.4) | 0.0152 | 38.9 (6.4) | 36.9 (5.9) | 0.9528 |
Platelet (X1000/ml) | 280.3 (58.0) | 299.5 (110.0) | 0.3139 | 318.2 (139.3) | 293.5 (118.8) | 0.8590 |
Albumin (g/dl) | 4.1 (0.3) | 3.6 (0.7) | 0.0077 | 3.9 (0.4) | 3.2 (0.6) | 0.0687 |
Aspartate Aminotransferase (IU/l) | 41.2 (47.9) | 44.4 (32.4) | 0.6784 | 23.2 (4.6) | 31.8 (13.6) | 0.1282 |
Alanine Aminotransferase (IU/l) | 36.6 (43.2) | 39.0 (36.2) | 0.4838 | 19.7 (6.8) | 18.0 (6.0) | 0.6784 |
Lactate Dehydrogenase (IU/l) | 250.7 (45.3) | 311.6 (86.2) | 0.1386 | 215.2 (23.8) | 383.6 (158.3) | 0.0209 |
Alkaline Phosphatase (IU/l) | 278.1 (141.2) | 239.3 (97.9) | 0.7794 | 243.8 (89.5) | 261.8 (90.2) | 0.9528 |
γ-glutamyltransferase (IU/l) | 52.2 (44.4) | 179.5 (392.2) | 0.1551 | 26.3 (18.0) | 31.1 (14.9) | 0.4990 |
Creatinine (mg/dl) | 0.7 (0.1) | 0.7 (0.1) | 0.8127 | 0.6 (0.1) | 0.7 (0.2) | 0.8127 |
Blood Urea Nitrogen (mg/dl) | 13.9 (2.3) | 17.1 (6.2) | 0.1097 | 14.4 (3.1) | 16.8 (3.5) | 0.4008 |
C-reactive protein (mg/dl) | 2.1 (2.3) | 6.4 (10.1) | 0.1097 | 3.9 (4.1) | 11.2 (7.7) | 0.2135 |
KL-6 (U/ml) | 2078.1 (2525.4) | 2105.8 (2495.5) | 0.0280 | 431.0 (256.6) | 799.7 (425.9) | 0.0208 |
Surfactant Protein-D (ng/ml) | 160.7 (126.5) | 194.7 (123.2) | 0.1763 | 76.4 (53.5) | 170.5 (163.6) | 0.0619 |
TIMP-1 (pg/ml) | 192899 (54474) | 245030 (93165) | 0.3105 | 218303 (58054) | 313999 (91931) | 0.0166 |
TIMP-2 (pg/ml) | 123534 (24219) | 100422 (12693) | 0.1763 | 120044 (21985) | 102973 (21694) | 0.0125 |
TIMP-3 (pg/ml) | 16813 (5411) | 18791 (9923) | 0.7353 | 14857 (14822) | 13457 (5240) | 0.1097 |
MMP-3 (pg/ml) | 587882 (245290) | 628244 (328962) | 0.5940 | 1025348 (787427) | 416640 (271619) | 0.0019 |
MMP-9 (pg/ml) | 2852316 (1698909) | 2800269 (1205613) | 0.5940 | 2463095 (1473636) | 2860985 (1837002) | 0.5509 |
Osteopontin (pg/ml) | 12464 (10678) | 28442 (35397) | 0.0663 | 15979 (13604) | 31356 (32402) | 0.0736 |
Eotaxin2 (pg/ml) | 3953 (2312) | 5311 (5724) | 0.3139 | 4846 (3566) | 3523 (4453) | 0.0258 |
IL-1RA (pg/ml) | 94 (111) | 417 (653) | 0.0796 | 196 (409) | 390 (346) | 0.2209 |
IL-2Rα (pg/ml) | 2611 (1669) | 3689 (2047) | 0.0506 | 4274 (2147) | 9899 (7159) | 0.0076 |
IL-6 (pg/ml) | 37 (47) | 238 (422) | 0.0209 | 145 (290) | 444 (952) | 0.2455 |
MMP-1 (pg/ml) | 26532 (18626) | 44551 (43273) | 0.1097 | 97389 (100090) | 95411 (58164) | 0.0962 |
MMP-8 (pg/ml) | 24640 (18134) | 49581 (74715) | 0.3743 | 26573 (17394) | 48134 (36641) | 0.1401 |
MMP-3/MMP-1 | 29.78 (16.71) | 29.11 (24.88) | 0.7671 | 17.07 (17.98) | 5.92 (4.81) | 0.0043 |
Association of serum biomarker profile with outcome
Died (n = 9) | Survived (n = 14) | |||||
---|---|---|---|---|---|---|
Stable | AoDILD |
P
| Stable | AoDILD |
P
| |
White Blood Cell count(X1000/ml) | 8.5 (1.7) | 10.4 (1.8) | 0.138 | 11.4 (3.6) | 13.0 (3.7) | 0.279 |
Red Blood Cell count(X106/ml) | 4.3 (0.3) | 3.9 (0.7) | 0.043 | 4.1 (0.8) | 4.4 (0.6) | 0.069 |
Hemoglobin(g/dl) | 13.7 (1.2) | 11.7 (2.7) | 0.043 | 12.7 (2.0) | 12.9 (1.7) | 0.108 |
Hematocrit(%) | 41.5 (3.5) | 35.6 (6.7) | 0.043 | 40.1 (5.8) | 39.2 (5.4) | 0.917 |
Platelet(X1000/ml) | 266.0 (62.5) | 310.1 (131.2) | 0.281 | 312.1 (119.0) | 287.1 (102.4) | 0.972 |
Albumin(g/dl) | 3.9 (0.2) | 3.0 (0.6) | 0.068 | 4.1 (0.5) | 3.6 (0.5) | 0.005 |
Aspartate Aminotransferase(IU/l) | 54.2 (60.6) | 43.3 (34.2) | 0.893 | 23.8 (6.8) | 33.5 (14.0) | 0.068 |
Alanine Aminotransferase(IU/l) | 47.0 (55.2) | 34.1 (38.9) | 0.500 | 20.8 (7.8) | 22.6 (11.1) | 0.480 |
Lactate Dehydrogenase(IU/l) | 234.0 (32.2) | 361.8 (92.8) | 0.138 | 232.5 (43.0) | 346.2 (158.2) | 0.039 |
Alkaline Phosphatase(IU/l) | 320.2 (169.8) | 224.9 (67.2) | 0.144 | 238.2 (82.4) | 268.5 (103.1) | 0.221 |
γ-glutamyltransferase(IU/l) | 42.4 (32.7) | 179.1 (413.2) | 0.419 | 38.1 (37.5) | 42.8 (44.2) | 0.142 |
Creatinine(mg/dl) | 0.7 (0.1) | 0.7 (0.2) | 0.419 | 0.7 (0.1) | 0.7 (0.1) | 0.422 |
Blood Urea Nitrogen(mg/dl) | 13.1 (2.5) | 15.1 (5.2) | 0.715 | 14.5 (2.7) | 18.1 (4.3) | 0.039 |
C-reactive protein(mg/dl) | 0.8 (0.5) | 12.0 (8.6) | 0.080 | 3.8 (3.7) | 7.3 (9.0) | 0.311 |
KL-6(U/ml) | 1364.1 (2423.4) | 1565.4 (2498.4) | 0.025 | 837.5 (936.0) | 1173.8 (898.0) | 0.017 |
Surfactant Protein-D(ng/ml) | 136.8 (125.6) | 196.0 (114.4) | 0.036 | 87.1 (60.4) | 169.6 (167.8) | 0.203 |
TIMP-1(pg/ml) | 231906 (68528) | 346576 (72337) | 0.080 | 197816 (49624) | 260193 (96764) | 0.084 |
TIMP-2(pg/ml) | 118406 (27648) | 105669 (20160) | 0.345 | 122762 (20616) | 100361 (17629) | 0.012 |
TIMP-3(pg/ml) | 10668 (6632) | 15759 (12498) | 0.043 | 17743 (12977) | 15609 (4998) | 0.790 |
MMP-3(pg/ml) | 752633 (495718) | 513110 (247738) | 0.214 | 919436 (751496) | 490655 (348157) | 0.030 |
MMP-9(pg/ml) | 1769108 (1012232) | 3358493 (1977141) | 0.011 | 3159443 (1634403) | 2502127 (1229009) | 0.140 |
Osteopontin(pg/ml) | 13588 (9212) | 51660 (44658) | 0.008 | 15256 (14407) | 16430 (9537) | 0.551 |
Eotaxin 2(pg/ml) | 4854 (4321) | 4320 (5943) | 0.110 | 4267 (2079) | 4160 (4408) | 0.096 |
IL-1RA(pg/ml) | 224 (463) | 657 (559) | 0.086 | 112 (190) | 236 (352) | 0.445 |
IL-2Rα(pg/ml) | 3827 (2213) | 8408 (4328) | 0.011 | 3492 (2072) | 6865 (7488) | 0.064 |
IL-6(pg/ml) | 156 (339) | 710 (1157) | 0.066 | 69 (115) | 140 (222) | 0.328 |
MMP-1(pg/ml) | 35772 (19709) | 73909 (39388) | 0.011 | 91449 (103647) | 76538 (67816) | 0.397 |
MMP-8 (pg/ml) | 14814 (12583) | 51014 (40613) | 0.008 | 32889 (16905) | 47213 (62177) | 0.826 |
MMP-3/MMP-1 | 23.67 (18.54) | 10.29 (8.39) | 0.028 | 21.00 (18.50) | 18.02 (23.73) | 0.221 |