J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 12, Number 1, January 2020, pages 6-12

Association Between Serological Markers and Crohn’s Disease Activity

**Table 1.** Baseline Characteristics of Patients
	Crohn’s patients with SGI at baseline
SD: standard deviation; SGI: serum genetic inflammatory; TNF: tumor necrosis factor; VD: vedolizumab; UST: ustekinumab; MTX: methotrexate; UGI: upper gastrointestinal; BMI: body mass index; PPI: proton pump inhibitor.
Age, mean (SD)	43.9 (15.7)
Sex, N (%)
Females	85 (63%)
Males	50 (37%)
Race, N (%)
Caucasians	82 (60.7%)
African Americans	49 (36.3%)
Others	4 (3.0%)
Duration of disease in years, mean (SD)	9.6 (11.0)
Steroid use, N (%)	57 (42.5%)
Tobacco use, N (%)	30 (22.4%)
TNF blocker use, N (%)	87 (64.9%)
VD use, N (%)	20 (14.9%)
UST use, N (%)	36 (26.9%)
Thiopurine, N (%)	21 (15.7%)
MTX, N (%)	16 (11.9%)
Crohn’s behavior, N (%)
Penetrating	52 (38.8%)
Stricturing	35 (26.1%)
None	47 (35.1%)
Perianal, N (%)	40 (29.9%)
UGI, N (%)	30 (22.4%)
Crohn’s location, N (%)
Ileal	23 (17%)
Colonic	39 (28.9%)
Ileocolonic	72 (53.3%)
BMI, mean (SD)	26.8 (7.2)
Obesity, N (%)	48 (35.8%)
PPI use, N (%)	42 (31.3%)

Table 1. Baseline Characteristics of Patients

Crohn’s patients with SGI at baseline

SD: standard deviation; SGI: serum genetic inflammatory; TNF: tumor necrosis factor; VD: vedolizumab; UST: ustekinumab; MTX: methotrexate; UGI: upper gastrointestinal; BMI: body mass index; PPI: proton pump inhibitor.

Age, mean (SD)

43.9 (15.7)

Sex, N (%)

Females

85 (63%)

Males

50 (37%)

Race, N (%)

Caucasians

82 (60.7%)

African Americans

49 (36.3%)

Others

4 (3.0%)

Duration of disease in years, mean (SD)

9.6 (11.0)

Steroid use, N (%)

57 (42.5%)

Tobacco use, N (%)

30 (22.4%)

TNF blocker use, N (%)

87 (64.9%)

VD use, N (%)

20 (14.9%)

UST use, N (%)

36 (26.9%)

Thiopurine, N (%)

21 (15.7%)

MTX, N (%)

16 (11.9%)

Crohn’s behavior, N (%)

Penetrating

52 (38.8%)

Stricturing

35 (26.1%)

None

47 (35.1%)

Perianal, N (%)

40 (29.9%)

UGI, N (%)

30 (22.4%)

Crohn’s location, N (%)

Ileal

23 (17%)

Colonic

39 (28.9%)

Ileocolonic

72 (53.3%)

BMI, mean (SD)

26.8 (7.2)

Obesity, N (%)

48 (35.8%)

PPI use, N (%)

42 (31.3%)

**Table 2.** Characteristics of Sample of Crohn’s Patients by Anti-CBir1 IgG Category
	Low anti-CBir1 IgG	High anti-CBir1 IgG	P value
^aTwo sample t-test; ^bChi-square; ^cFisher’s exact; ^dWilcoxon rank sum. SD: standard deviation; TNF: tumor necrosis factor; VD: vedolizumab; UST: ustekinumab; MTX: methotrexate; UGI: upper gastrointestinal; BMI: body mass index; PPI: proton pump inhibitor.
Age, mean (SD)	45.4 (15.8)	39.7(14.8)	0.0692^a
Sex, N (%)			0.2871^b
Females	61 (60.4%)	24 (70.6%)
Males	40 (39.6%)	10 (29.4%)
Race, N (%)			0.2417^c
Caucasians	64 (63.4%)	18 (52.9%)
African Americans	35 (34.7%)	14 (41.2%)
Others	2 (2.0%)	2 (5.9%)
Duration of disease in years, mean (SD)	9.7 (11.0)	9.3 (11.3)	0.8989^d
Steroid use, N (%)	38 (37.6%)	19 (57.6%)	0.0441^b
Tobacco use, N (%)	22 (21.8%)	8 (24.2%)	0.7685^b
TNF blocker use, N (%)	65 (64.4%)	22 (66.7%)	0.8092^b
VD use, N (%)	15 (14.9%)	5 (15.2%)	0.9665^b
UST use, N (%)	27 (26.7%)	9 (27.3%)	0.9515^b
Thiopurine, N (%)	13 (12.9%)	8 (24.2%)	0.1188^b
MTX, N (%)	13 (12.9%)	3 (9.1%)	0.5609^b
Crohn’s behavior, N (%)			0.5271^b
Penetrating	37 (36.6%)	15 (45.5%)
Stricturing	26 (25.7%)	9 (27.3%)
None	38 (37.6%)	9 (27.3%)
Perianal, N (%)	31 (30.7%)	9 (27.3%)	0.7093^b
UGI, N (%)	21 (20.8%)	9 (27.3%)	0.4381^b
Crohn’s location, N (%)			0.0251^b
Ileal	17 (16.8%)	6 (17.6%)
Colonic	35 (34.7%)	4 (11.8%)
Ileocolonic	49 (48.5%)	23 (67.6%)
BMI, mean (SD)	27.3 (7.1)	25.3 (7.7)	0.1849^a
Obesity, N (%)	39 (38.6%)	9 (27.3%)	0.2381^b
PPI use, N (%)	34 (33.7%)	8 (24.2%)	0.3111^b

Table 2. Characteristics of Sample of Crohn’s Patients by Anti-CBir1 IgG Category

Low anti-CBir1 IgG

High anti-CBir1 IgG

P value

^aTwo sample t-test; ^bChi-square; ^cFisher’s exact; ^dWilcoxon rank sum. SD: standard deviation; TNF: tumor necrosis factor; VD: vedolizumab; UST: ustekinumab; MTX: methotrexate; UGI: upper gastrointestinal; BMI: body mass index; PPI: proton pump inhibitor.

Age, mean (SD)

45.4 (15.8)

39.7(14.8)

0.0692^a

Sex, N (%)

0.2871^b

Females

61 (60.4%)

24 (70.6%)

Males

40 (39.6%)

10 (29.4%)

Race, N (%)

0.2417^c

Caucasians

64 (63.4%)

18 (52.9%)

African Americans

35 (34.7%)

14 (41.2%)

Others

2 (2.0%)

2 (5.9%)

Duration of disease in years, mean (SD)

9.7 (11.0)

9.3 (11.3)

0.8989^d

Steroid use, N (%)

38 (37.6%)

19 (57.6%)

0.0441^b

Tobacco use, N (%)

22 (21.8%)

8 (24.2%)

0.7685^b

TNF blocker use, N (%)

65 (64.4%)

22 (66.7%)

0.8092^b

VD use, N (%)

15 (14.9%)

5 (15.2%)

0.9665^b

UST use, N (%)

27 (26.7%)

9 (27.3%)

0.9515^b

Thiopurine, N (%)

13 (12.9%)

8 (24.2%)

0.1188^b

MTX, N (%)

13 (12.9%)

3 (9.1%)

0.5609^b

Crohn’s behavior, N (%)

0.5271^b

Penetrating

37 (36.6%)

15 (45.5%)

Stricturing

26 (25.7%)

9 (27.3%)

None

38 (37.6%)

9 (27.3%)

Perianal, N (%)

31 (30.7%)

9 (27.3%)

0.7093^b

UGI, N (%)

21 (20.8%)

9 (27.3%)

0.4381^b

Crohn’s location, N (%)

0.0251^b

Ileal

17 (16.8%)

6 (17.6%)

Colonic

35 (34.7%)

4 (11.8%)

Ileocolonic

49 (48.5%)

23 (67.6%)

BMI, mean (SD)

27.3 (7.1)

25.3 (7.7)

0.1849^a

Obesity, N (%)

39 (38.6%)

9 (27.3%)

0.2381^b

PPI use, N (%)

34 (33.7%)

8 (24.2%)

0.3111^b

**Table 3.** Characteristics of Sample of Crohn’s Patients by Anti-A4Fla2IgG Category
	Low anti-A4Fla2 IgG	High anti-A4Fla2 IgG	P value
^aTwo sample t-test; ^bChi-square; ^cFisher’s exact; ^dWilcoxon rank sum. SD: standard deviation; TNF: tumor necrosis factor; VD: vedolizumab; UST: ustekinumab; MTX: methotrexate; UGI: upper gastrointestinal; BMI: body mass index; PPI: proton pump inhibitor.
Age, mean (SD)	45.5 (15.6)	41.1 (15.7)	0.1170^a
Sex, N (%)			0.1596^b
Females	51 (58.6%)	34 (70.8%)
Males	36 (41.4%)	14 (29.2%)
Race, N (%)			0.0058^c
Caucasians	61 (70.1%)	21 (43.8%)
African Americans	24 (27.6%)	25 (52.1%)
Others	2 (2.2%)	2 (4.2%)
Duration of disease in years, mean (SD)	9.0 (10.8)	10.7 (11.5)	0.1410^d
Steroid use, N (%)	35 (40.7%)	22 (45.8%)	0.5642^b
Tobacco use, N (%)	19 (22.1%)	11 (22.9%)	0.9127^b
TNF blocker use, N (%)	53 (61.6%)	34 (70.8%)	0.2843^b
VD use, N (%)	14 (16.3%)	6 (12.5%)	0.5561^b
UST use, N (%)	23 (26.7%)	13 (27.1%)	0.9661^b
Thiopurine, N (%)	10 (11.6%)	11 (22.9%)	0.0848^b
MTX, N (%)	12 (14.0%)	4 (8.3%)	0.3361^b
Crohn’s behavior, N (%)			0.6640^b
Penetrating	31 (36.0%)	21 (43.8%)
Stricturing	23 (26.7%)	12 (25.0%)
None	32 (37.2%)	15 (31.3%)
Perianal, N (%)	24 (27.9%)	16 (33.3%)	0.5104^b
UGI, N (%)	17 (19.8%)	13 (27.1%)	0.3300^b
Crohn’s location, N (%)			0.0245^b
Ileal	18 (20.7%)	5 (10.4%)
Colonic	30 (34.5%)	9 (18.8%)
Ileocolonic	38 (43.7%)	34 (70.8%)
BMI, mean (SD)	26.9 (7.0)	26.6 (7.6)	0.8295^a
Obesity, N (%)	32 (37.2%)	16 (33.3%)	0.6537^b
PPI use, N (%)	31 (36.0%)	11 (22.9%)	0.1162^b

Table 3. Characteristics of Sample of Crohn’s Patients by Anti-A4Fla2IgG Category

Low anti-A4Fla2 IgG

High anti-A4Fla2 IgG

P value

Age, mean (SD)

45.5 (15.6)

41.1 (15.7)

0.1170^a

Sex, N (%)

0.1596^b

Females

51 (58.6%)

34 (70.8%)

Males

36 (41.4%)

14 (29.2%)

Race, N (%)

0.0058^c

Caucasians

61 (70.1%)

21 (43.8%)

African Americans

24 (27.6%)

25 (52.1%)

Others

2 (2.2%)

2 (4.2%)

Duration of disease in years, mean (SD)

9.0 (10.8)

10.7 (11.5)

0.1410^d

Steroid use, N (%)

35 (40.7%)

22 (45.8%)

0.5642^b

Tobacco use, N (%)

19 (22.1%)

11 (22.9%)

0.9127^b

TNF blocker use, N (%)

53 (61.6%)

34 (70.8%)

0.2843^b

VD use, N (%)

14 (16.3%)

6 (12.5%)

0.5561^b

UST use, N (%)

23 (26.7%)

13 (27.1%)

0.9661^b

Thiopurine, N (%)

10 (11.6%)

11 (22.9%)

0.0848^b

MTX, N (%)

12 (14.0%)

4 (8.3%)

0.3361^b

Crohn’s behavior, N (%)

0.6640^b

Penetrating

31 (36.0%)

21 (43.8%)

Stricturing

23 (26.7%)

12 (25.0%)

None

32 (37.2%)

15 (31.3%)

Perianal, N (%)

24 (27.9%)

16 (33.3%)

0.5104^b

UGI, N (%)

17 (19.8%)

13 (27.1%)

0.3300^b

Crohn’s location, N (%)

0.0245^b

Ileal

18 (20.7%)

5 (10.4%)

Colonic

30 (34.5%)

9 (18.8%)

Ileocolonic

38 (43.7%)

34 (70.8%)

BMI, mean (SD)

26.9 (7.0)

26.6 (7.6)

0.8295^a

Obesity, N (%)

32 (37.2%)

16 (33.3%)

0.6537^b

PPI use, N (%)

31 (36.0%)

11 (22.9%)

0.1162^b

**Table 4.** Rate and Rate Ratios of CDA
Variables	Group	Total CDA	Total PY	CDA rate	Unadjusted RR (95% CI), P-value	Adjusted RR (95% CI), P-value
^aAdjusted for age, gender, race, duration of disease, TNF, CD behavior, perianal involvement, disease location and obesity. ^bAdjusted for age, gender, race, duration of disease, steroid, tobacco use, TNF, CD behavior and disease location. ^cAdjusted for age, gender, race, duration of disease, steroid, TNF, vedolizumab, CD behavior, perianal involvement, UGI involvement, disease location and PPI. ^dAdjusted for age, gender, race, duration of disease, steroid, thiopurine, CD behavior, disease location, obesity and PPI. ^eAdjusted for age, gender, race, duration of disease, TNF, MTX, thiopurine, UGI involvement, disease location and PPI. ^fAdjusted for age, gender, race, duration of disease, steroid, tobacco use, thiopurine, TNF, vedolizumab, UST, CD behavior, perianal involvement and disease location. CDA: Crohn’s disease activity; RR: rate ratio; CI: confidence interval; TNF: tumor necrosis factor; UST: ustekinumab; MTX: methotrexate; UGI: upper gastrointestinal; PPI: proton pump inhibitor.
By ASCA-IgA
Antibody ASCA-IgA (binary variable)	Low, 70	42	100	0.42 (0.31 - 0.57)
	High, 65	42	104	0.40 (0.30 - 0.55)	0.96 (0.63 - 1.47), 0.8480	0.83 (0.53 - 1.31), 0.4317^a
ASCA-IgA1 (10 units increase)					1.01 (0.95 - 1.06), 0.8004	0.99 (0.94 - 1.05), 0.8247^a
By ASCA-IgG
Antibody ASCA-IgG (binary variable)	Low, 76	46	113	0.41 (0.31 - 0.54)
	High, 59	38	91	0.42 (0.31 - 0.58)	1.03 (0.67 - 1.58), 0.8956	1.09 (0.66 - 1.79), 0.7334^b
ASCA-IgG1 (10 units increase)					1.01 (0.95 - 1.08), 0.7144	1.01 (0.93 - 1.08), 0.8798^b
By anti-OmpC IgA
Anti-OmpC IgA (binary variable)	Low, 104	62	150	0.41 (0.32 - 0.53)
	High, 31	22	53	0.42 (0.27 - 0.63)	1.01 (0.62 - 1.64), 0.9673	0.97 (0.56 - 1.69), 0.9217^c
Anti-OmpC IgA1 (10 units increase)					0.98 (0.85 - 1.12), 0.7633	0.96 (0.82 - 1.12), 0.6250^c
By anti-CBir1 IgG
Anti-CBir1 IgG (binary variable)	Low, 101	50	153	0.33 (0.25 - 0.43)
	High, 34	34	50	0.68 (0.49 - 0.95)	2.08 (1.35 - 3.22), 0.0010	2.06 (1.28 - 3.33), 0.0032^d
Anti-CBir1 IgG1 (10 units increase)					1.06 (0.99 - 1.13), 0.0982	1.05 (0.97 - 1.12), 0.2146^d
By anti-A4Fla2 IgG
Anti-A4Fla2 IgG (binary variable)	Low, 87	47	137	0.34 (0.26 - 0.46)
	High, 48	37	66	0.56 (0.41 - 0.78)	1.64 (1.07 - 2.53), 0.0238	1.55 (0.95 - 2.52), 0.0789^e
Anti-A4Fla2 IgG1 (10 units increase)					1.07 (1.00 - 1.14), 0.0490	1.06 (0.98 - 1.14), 0.1528^e
By anti-FlaX IgG
Anti-FlaX IgG (binary variable)	Low, 67	36	103	0.35 (0.25 - 0.48)
	High, 68	48	100	0.48 (0.36 - 0.64)	1.38 (0.89 - 2.12), 0.1471	1.22 (0.75 - 1.99), 0.4265^f
Anti-FlaX IgG1 (10 units increase)					1.05 (0.99 - 1.12), 0.1062	1.05 (0.98 - 1.13), 0.1709^f

Table 4. Rate and Rate Ratios of CDA

Variables

Group

Total CDA

Total PY

CDA rate

Unadjusted RR (95% CI), P-value

Adjusted RR (95% CI), P-value

^aAdjusted for age, gender, race, duration of disease, TNF, CD behavior, perianal involvement, disease location and obesity. ^bAdjusted for age, gender, race, duration of disease, steroid, tobacco use, TNF, CD behavior and disease location. ^cAdjusted for age, gender, race, duration of disease, steroid, TNF, vedolizumab, CD behavior, perianal involvement, UGI involvement, disease location and PPI. ^dAdjusted for age, gender, race, duration of disease, steroid, thiopurine, CD behavior, disease location, obesity and PPI. ^eAdjusted for age, gender, race, duration of disease, TNF, MTX, thiopurine, UGI involvement, disease location and PPI. ^fAdjusted for age, gender, race, duration of disease, steroid, tobacco use, thiopurine, TNF, vedolizumab, UST, CD behavior, perianal involvement and disease location. CDA: Crohn’s disease activity; RR: rate ratio; CI: confidence interval; TNF: tumor necrosis factor; UST: ustekinumab; MTX: methotrexate; UGI: upper gastrointestinal; PPI: proton pump inhibitor.

By ASCA-IgA

Antibody ASCA-IgA (binary variable)

Low, 70

100

0.42 (0.31 - 0.57)

High, 65

104

0.40 (0.30 - 0.55)

0.96 (0.63 - 1.47), 0.8480

0.83 (0.53 - 1.31), 0.4317^a

ASCA-IgA1 (10 units increase)

1.01 (0.95 - 1.06), 0.8004

0.99 (0.94 - 1.05), 0.8247^a

By ASCA-IgG

Antibody ASCA-IgG (binary variable)

Low, 76

113

0.41 (0.31 - 0.54)

High, 59

0.42 (0.31 - 0.58)

1.03 (0.67 - 1.58), 0.8956

1.09 (0.66 - 1.79), 0.7334^b

ASCA-IgG1 (10 units increase)

1.01 (0.95 - 1.08), 0.7144

1.01 (0.93 - 1.08), 0.8798^b

By anti-OmpC IgA

Anti-OmpC IgA (binary variable)

Low, 104

150

0.41 (0.32 - 0.53)

High, 31

0.42 (0.27 - 0.63)

1.01 (0.62 - 1.64), 0.9673

0.97 (0.56 - 1.69), 0.9217^c

Anti-OmpC IgA1 (10 units increase)

0.98 (0.85 - 1.12), 0.7633

0.96 (0.82 - 1.12), 0.6250^c

By anti-CBir1 IgG

Anti-CBir1 IgG (binary variable)

Low, 101

153

0.33 (0.25 - 0.43)

High, 34

0.68 (0.49 - 0.95)

2.08 (1.35 - 3.22), 0.0010

2.06 (1.28 - 3.33), 0.0032^d

Anti-CBir1 IgG1 (10 units increase)

1.06 (0.99 - 1.13), 0.0982

1.05 (0.97 - 1.12), 0.2146^d

By anti-A4Fla2 IgG

Anti-A4Fla2 IgG (binary variable)

Low, 87

137

0.34 (0.26 - 0.46)

High, 48

0.56 (0.41 - 0.78)

1.64 (1.07 - 2.53), 0.0238

1.55 (0.95 - 2.52), 0.0789^e

Anti-A4Fla2 IgG1 (10 units increase)

1.07 (1.00 - 1.14), 0.0490

1.06 (0.98 - 1.14), 0.1528^e

By anti-FlaX IgG

Anti-FlaX IgG (binary variable)

Low, 67

103

0.35 (0.25 - 0.48)

High, 68

100

0.48 (0.36 - 0.64)

1.38 (0.89 - 2.12), 0.1471

1.22 (0.75 - 1.99), 0.4265^f

Anti-FlaX IgG1 (10 units increase)

1.05 (0.99 - 1.12), 0.1062

1.05 (0.98 - 1.13), 0.1709^f