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©The Author(s) 2015.
World J Gastroenterol. Jun 14, 2015; 21(22): 6952-6964
Published online Jun 14, 2015. doi: 10.3748/wjg.v21.i22.6952
Published online Jun 14, 2015. doi: 10.3748/wjg.v21.i22.6952
Table 1 Prevalence and clinical significance of antiphospholipid antibodies in inflammatory bowel disease - review of the literature
Ref. | Study design | Group | n | ACA prevalence (%) | Anti-β2-GPI prevalence (%) | ACA | Anti-β2-GPI | ||||||||||||||||
Total | IgG | IgM | IgA | Total | IgG | IgM | IgA | Disease activity | Association with disease phenotype | TE event | IS therapy | Disease activity | Association with disease phenotype | TE event | IS therapy | ||||||||
Location | Complicated disease behaviour | Need for surgery | Location | Complicated disease behaviour | Need for surgery | ||||||||||||||||||
[19] | R | HC | 136 | 4.0 | |||||||||||||||||||
CD | 73 | 20.0 | No | No | No | No | No | ||||||||||||||||
UC | 63 | 10.0 | No | No | No | No | No | ||||||||||||||||
[20] | P | AS | 19 | 5.3 | 5.3 | 0 | 0 | 0 | |||||||||||||||
CD | 63 | 8.0 | 3.0 | 0 | 0 | 0 | No | No | |||||||||||||||
[21] | CS | CD | 22 | 36.0 | No | No | |||||||||||||||||
UC | 30 | 20.0 | No | No | |||||||||||||||||||
[22] | CS | CD | 50 | 22.0 | 10.0 | 6.0 | 6 | No | No | No | No | ||||||||||||
[23] | R | HC | 40 | 5.0 | |||||||||||||||||||
CD | 41 | 26.8 | No | No | |||||||||||||||||||
UC | 19 | 26.3 | No | No | |||||||||||||||||||
[24] | CS | HC | 261 | 1.2 | 1.2 | ||||||||||||||||||
UC | 80 | 10.0 | 17.5 | No | No | No | No | ||||||||||||||||
[25] | R&CS | HC | 100 | 3.0 | 2.0 | 1.0 | 0 | 0 | 0 | ||||||||||||||
CD | 45 | 15.6 | 8.9 | 6.7 | 4.4 | 2.2 | 2.2 | No | No | No | No | No | No | No | No | No | No | ||||||
UC | 83 | 18.1 | 13.3 | 4.8 | 10.8 | 8.4 | 2.4 | + | No | No | No | No | No | No | No | ||||||||
[26] | CS | HC | 118 | 2.5 | |||||||||||||||||||
CD | 138 | 11.0 | No | No | No | ||||||||||||||||||
[27] | CS | HC | 40 | ||||||||||||||||||||
CD | 7 | 3.9 | 0 | ||||||||||||||||||||
UC | 19 | ||||||||||||||||||||||
[28] | P | CD | 4 | 0 | No | ||||||||||||||||||
UC | 8 | 12.5 | |||||||||||||||||||||
[29] | R | HC | 102 | ||||||||||||||||||||
CD | 24 | 6.6 | No | ||||||||||||||||||||
UC | 21 | ||||||||||||||||||||||
[30] | R | HC | 53 | 0 | 0 | ||||||||||||||||||
CD | 29 | 9.4 | 6.9 | ||||||||||||||||||||
UC | 24 | 12.5 | |||||||||||||||||||||
[31] | R | HC | 100 | ||||||||||||||||||||
CD | 26 | 0 | 0 | ||||||||||||||||||||
UC | 75 | 1.3 | 1.3 | ||||||||||||||||||||
[32] | CS | IBD | 20 | 30.0 | |||||||||||||||||||
[33] | CS | HC | 27 | 0 | 0 | ||||||||||||||||||
CD | 5 | 7.4 | 3.7 | ||||||||||||||||||||
UC | 22 |
Table 2 Clinical characteristics of inflammatory bowel disease patients at time of inclusion n (%)
CD | UC | ||
(n = 271) | (n = 187) | ||
Male/female (n) | 115/156 | 86/101 | |
Age (yr)1 | 31 (24.0-41.0) | 40 (29.0-52.0) | |
Age at presentation (yr)1 | 25 (19.0-33.0) | 33 (23.0-43.0) | |
Duration (yr)1 | 4 (1.0-9.0) | 4 (1.0-11.0) | |
Familial IBD | 12 (4.4) | 6 (3.2) | |
Location | |||
L1 | 46 (17.0) | Proctitis | 30 (16.0) |
L2 | 67 (24.7) | Left-sided | 104 (55.6) |
L3 | 157 (57.9) | Extensive | 53 (28.3) |
L4 only | 1 (0.4) | ||
All L4 | 18 | ||
Behavior | |||
B1 | 154 (56.5) | Remitting | 174 (93.0) |
B2 | 56 (20.7) | Continuous | 12 (6.4) |
B3 | 61 (22.5) | Prolonged remission | 1 (0.5) |
Perianal disease | 76 (27.5) | - | |
Arthritis | 54 (19.9) | 26 (13.9) | |
Ocular manifestations | 65 (24.0) | 12 (6.4) | |
Cutaneous manifestation | 35 (12.9) | 16 (8.6) | |
PSC | 9 (3.3) | 8 (4.3) | |
Steroid use/refractory | 242 (89.3)/32 (13.2) | 144 (77.0)/11 (7.6) | |
Azathioprine use | 196 (72.3) | 66 (35.3) | |
Surgery/multiple in CD | 54 (19.6)/19 (7.0) | 7 (3.7) | |
Biological use | 106 (39.1) | 25 (13.4) | |
Smoking habits | |||
never | 219 (80.8) | 167 (89.3) | |
yes | 47 (17.3) | 18 (9.6) | |
previous | 5 (1.8) | 2 (1.1) | |
Disease activity | |||
Inactive HBI ≤ 4 | 199 (73.4) | Inactive partial Mayo ≤ 3 | 135 (72.2) |
Active partial Mayo > 4 | |||
Active HBI ≥ 5 | 72 (26.6) | 52 (27.8) |
Table 3 Anti-phospholipid antibodies in patients with Crohn’s disease, ulcerative colitis, and healthy controls n (%)
CD (n = 265) | UC (n = 186) | HC (n = 103) | |
Anti-β2-GPI IgG | 5 (1.9) | 4 (2.2) | 2 (1.9) |
Anti-β2-GPI IgM | 8 (3.0) | 12 (6.5) | 3 (2.9) |
Anti-β2-GPI IgA | 7 (2.6) | 7 (3.8) | 3 (2.9) |
Any anti-β2-GPI | 19 (7.2) | 18 (9.7) | 8 (7.8) |
ACA IgG | 27 (10.2)bd | 4 (2.2)d | 2 (1.9)b |
ACA IgM | 8 (3.0) | 4 (2.2) | 1 (1.0) |
ACA IgA | 51 (19.2)bd | 1 (0.5)d | 0 (0.0)b |
Any ACA | 62 (23.4)bd | 9 (4.8)d | 3 (2.9)b |
Anti-PS/PT IgG | 20 (7.5) | 9 (4.8) | 9 (8.7) |
Anti-PS/PT IgM | 25 (9.4)bc | 8 (4.3)c | 1 (1.0)b |
Anti-PS/PT IgA | 24 (9.1)c | 7 (3.8)c | 9 (8.7) |
Any anti-PS/PT | 54 (20.4)d | 19 (10.2)d | 16 (15.5) |
Table 4 Antiphospholipid antibodies and clinical characteristics of complication and surgery naïve Crohn’s disease patient cohort n (%)
Factor | Follow-up of CD B1 at first sampling total cohort (n = 143) | |||||
CD B1 total | No complication | Perianal change only (B1p) | Behaviour change to B2 or B3 | No surgery | Surgery | |
(n = 143) | (n = 114) | (n = 7) | (n = 22) | (n = 130) | (n = 13) | |
Male/female (n) | 60/83 | 45/69 | 5/2 | 10/12 | 55/75 | 5/8 |
Age at presentation (yr)1 | 25 (19.0-34.0) | 26 (20.0-34.3) | 17 (14.0-31.0) | 25 (18.8-34.8) | 25 (19.0-34.0) | 31 (18.0-35.5) |
Duration (yr)1 | 3 (1.0-6.0) | 2 (1.0-7.0) | 3 (1.0-5.0) | 3 (1.0-5.0) | 2 (1.0-6.0) | 3 (1.0-10.0) |
Location | ||||||
L1 | 30 (21.0) | 24 (21.1) | 0 (0.0) | 6 (27.3) | 26 (20.0) | 4 (30.8) |
L2 | 51 (35.7) | 44 (38.6) | 3 (42.9) | 4 (18.2) | 48 (36.9) | 3 (23.1) |
L3 | 62 (43.3) | 46 (40.4) | 4 (57.1) | 12 (54.5) | 56 (43.1) | 6 (46.2) |
L4 only | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Frequent relapse | 27 (18.9) | 18 (15.8)2 | 4 (57.1)2 | 5 (22.7) | 23 (17.7) | 4 (30.8) |
Smoking habit yes | 21 (16.2) | 14 (12.3)2 | 2 (28.6) | 8 (36.4)2 | 21 (16.2) | 3 (23.1) |
Follow up time from first sampling, mo1 | 53.4 (38.0-79.3) | 51.7 (36.9-73.9) | 79.8 (42.9-91.4) | 64.7 (45.6-85.0) | 50.93 (37.25-74.2) | 84.03 (60.0-91.7) |
Positive markers | ||||||
Anti-β2-GPI IgG | 1.4 | 1.8 | 0 | 0 | 1.6 | 0 |
Anti-β2-GPI IgM | 5.0 | 5.3 | 16.7 | 0 | 5.5 | 0 |
Anti-β2-GPI IgA | 2.8 | 1.8 | 16.7 | 4.5 | 3.1 | 0 |
Any anti-β2-GPI | 8.5 | 8.8 | 16.7 | 4.5 | 9.4 | 0 |
ACA IgG | 9.2 | 11.5 | 0 | 0 | 10.2 | 0 |
ACA IgM | 2.8 | 3.5 | 0 | 0 | 3.1 | 0 |
ACA IgA | 17.0 | 18.6 | 33.3 | 4.5 | 18.8 | 0 |
Any ACA | 19.9 | 22.1 | 33.3 | 4.5 | 21.9 | 0 |
Anti-PS/PT IgG | 8.5 | 8.0 | 0 | 13.6 | 7.8 | 15.4 |
Anti-PS/PT IgM | 7.8 | 8.8 | 16.7 | 0 | 7.8 | 7.7 |
Anti-PS/PT IgA | 9.9 | 9.7 | 16.7 | 9.1 | 10.9 | 0 |
Any anti-PS/PT | 20.6 | 19.5 | 33.3 | 22.7 | 20.3 | 23.1 |
Table 5 Univariate Kaplan Meier and Log-rank analysis of serologic and clinical factor associated with complicated disease course in B1 Crohn’s disease patients (n = 143)
Variable | Internal penetrating and/or stricturing complication | Perianal penetrating complication | CD-related abdominal surgery | |||
HR (95%CI) | PLogRank-value | HR (95%CI) | PLogRank-value | HR (95%CI) | PLogRank-value | |
Gender - male | 1.10 (0.47-2.55) | 0.83 | 2.69 (0.80-9.03) | 0.11 | 0.91 (0.33-2.55) | 0.86 |
Smoking | 3.72 (1.23-11.21)1 | 0.021 | 1.61 (0.36-7.19) | 0.53 | 1.64 (0.45-5.97) | 0.45 |
Location (colon only) | 0.41 (0.17-0.96)1 | 0.041 | 1.00 (0.29-3.43) | 0.99 | 0.61 (0.22-1.74) | 0.36 |
Frequent relapse | 1.10 (0.39-3.07) | 0.85 | 7.29 (1.72-30.99)1 | 0.0071 | 1.64 (0.44-6.10) | 0.46 |
APLA at all | 1.36 (0.59-3.16) | 0.47 | 1.30 (0.40-4.27) | 0.66 | 1.37 (0.49-3.80) | 0.55 |
Anti-β2-GPI at all | 0.56 (0.13-2.32) | 0.42 | 0.99 (0.13-7.70) | 0.99 | 0.33 (0.06-1.81) | 0.20 |
ACA at all | 0.41 (0.13-1.26) | 0.12 | 1.12 (0.23-5.49) | 0.89 | 0.30 (0.07-1.27) | 0.10 |
Anti-PS/PT at all | 1.07 (0.39-2.97) | 0.89 | 1.74 (0.38-8.03) | 0.48 | 1.11 (0.29-4.18) | 0.88 |
Table 6 Antiphospholipid antibodies, thrombophilia markers and clinical characteristics of total Crohn’s disease according to presence and type of thrombosis n (%)
Factor | Follow-up of CD Total Cohort from diagnosis (n = 265) | ||||
No thrombosis | Arterial thrombosis | Venous thrombosis | No pregnancy loss | Pregnancy loss | |
(n = 251) | (n = 3) | (n = 11) | (n = 146) | (n = 10) | |
Male/female | 104/147 | 1/2 | 7/4 | 146/0 | 10/0 |
Age at presentation (yr)1 | 25.0 (19.0-33.0) | 40.0 (28.0-42.0) | 29.5 (23.3-39.3) | 26.0 (20.0-35.0) | 25.5 (21.0-35.0) |
Frequent relapse | 48 (20.2) | 0 (0.0) | 4 (36.4) | 33 (24.1) | 2 (20.0) |
Previous thrombosis | 1 (0.4)3 | 0 (0.0) | 4 (36.4)3 | 2 (1.4) | 0 (0.0) |
Smoking habits yes | 48 (19.1) | 0 (0.0) | 3 (27.3) | 22 (15.1) | 2 (20.0) |
Follow up time from diagnosis, mo1 | 102.2 (63.3-172.8)2 | 149.9 (130.8-219.8) | 186.3 (142.0-244.2)2 | 109.0 (61.8-184.6) | 136.5 (95.4-180.6) |
Positive markers (%) | |||||
Anti-β2-GPI IgG and/or IgM | 4.8 | 0 | 9.1 | 4.9 | 10 |
Anti-β2-GPI IgA | 2.8 | 0 | 0 | 4.9 | 0 |
ACA IgG and/or IgM | 12.1 | 0 | 27.3 | 13.9 | 10 |
ACA IgA | 19.0 | 66.7 | 0 | 20.1 | 10 |
Anti-PS/PT IgG and/or IgM | 14.6 | 50.0 | 36.4 | 18.3 | 40 |
Anti-PS/PT IgA | 8.9 | 50.0 | 9.1 | 7.7 | 10 |
At least 1 APLA pos | 48.0 | 66.7 | 54.5 | 52.8 | 60 |
At least 2 APLA pos | 16.1 | 33.3 | 9.1 | 18.1 | 10 |
At least 3 APLA pos | 3.2 | 0 | 9.1 | 4.9 | 0 |
Thrombophilia markers3 (%) | |||||
LA | 7.5 | 0 | 0 | 5.1 | 0 |
PS deficiency (inherited and/or acquired) | 8.1 | 0 | 25.0 | 12.7 | 0 |
ATIII deficiency (inherited and/or acquired) | 0 | 0 | 0 | 0 | 0 |
PC deficiency (inherited and/or acquired) | 3.0 | 0 | 0 | 4.8 | 0 |
FV Leiden | 5.94 | 0 | 42.94 | 7.8 | 0 |
FII20210A | 5.9 | 0 | 16.7 | 7.8 | 0 |
Table 7 Stability of antiphospholipid antibodies marker status over time in inflammatory bowel diseases patients with at least 2 samples during the disease course n (%)
APLA marker | CD (n = 198) | UC (n = 103) |
Anti-β2-GPI IgG | ||
Stable negative | 194 (98.0) | 97 (94.2) |
Stable positive | 1 (0.5) | 2 (1.9) |
Neg. to pos. | 0 (0.0) | 3 (2.9) |
Pos. to neg. | 3 (1.5) | 1 (1.0) |
Anti-β2-GPI IgM | ||
Stable negative | 186 (94.0) | 94 (91.3) |
Stable positive | 4 (2.0) | 3 (2.9) |
Neg. to pos. | 6 (3.0) | 5 (4.9) |
Pos. to neg. | 2 (1.0) | 1 (0.9) |
Anti-β2-GPI IgA | ||
Stable negative | 190 (96.0) | 93 (90.3) |
Stable positive | 1 (0.5) | 4 (3.9) |
Neg. to pos. | 3 (1.5) | 5 (4.9) |
Pos. to neg. | 4 (2.0) | 1 (0.9) |
ACA IgG | ||
Stable negative | 139 (70.2) | 95 (92.2) |
Stable positive | 3 (1.5) | 1 (1.0) |
Neg. to pos. | 42 (21.2) | 6 (5.8) |
Pos. to neg. | 14 (7.1) | 1 (1.0) |
ACA IgM | ||
Stable negative | 173 (87.4) | 95 (92.2) |
Stable positive | 3 (1.5) | 1 (1.0) |
Neg. to pos. | 18 (9.1) | 7 (6.8) |
Pos. to neg. | 4 (2.0) | 0 (0.0) |
ACA IgA | ||
Stable negative | 73 (36.9) | 78 (75.7) |
Stable positive | 13 (6.6) | 0 (0.0) |
Neg. to pos. | 93 (46.9) | 24 (23.3) |
Pos. to neg. | 19 (9.6) | 1 (1.0) |
- Citation: Sipeki N, Davida L, Palyu E, Altorjay I, Harsfalvi J, Antal Szalmas P, Szabo Z, Veres G, Shums Z, Norman GL, Lakatos PL, Papp M. Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn’s disease. World J Gastroenterol 2015; 21(22): 6952-6964
- URL: https://www.wjgnet.com/1007-9327/full/v21/i22/6952.htm
- DOI: https://dx.doi.org/10.3748/wjg.v21.i22.6952