VoL 27, No. 5 Printed in Japan
Gastroenterologia Japonica Copyright 9 1992 by The Japanese Society of Gastroenterology
Significance of serum sialic acid in patients with Crohn's disease Rika BABA, Kurato YASHIRO, Kou NAGASAKO, and Hiroshi OBATA Institute of Gastroenterology, Tokyo Women's Medical College, Tokyo, Japan Summary: Serum sialic acid was measured to evaluate the activity of Crohn's disease. The sialic acid levels of patients with Crohn's disease in remission (CRP 0.0 mg/dl) were significantly higher than those of healthy subjects and postoperative patients with Crohn's disease. In patients in remission, serum sialic acid was significantly correlated with hemoglobin, hematocrit, platelet, and rapid turnover protein. Correlations with platelet, retinol-binding protein, and prealbumin were especially strong. From these findings, it was concluded that serum sialic acid level provides a useful index of the activity of Crohn's disease. Gastroenterol Jpn 1992;27:604-610. Key words: Crohn's disease; platelet count; rapid turnover protein; serum sialic acid.
Introduction
Materials and Methods
In asymptomatic cases, the activity of Crohn's disease is difficult to estimate. Serum C-reactive protein (CRP) is too low to provide a useful index of the disease activity. However, the predictability of relapse is important in maintenance therapy. Sialic acid is included in acute phase reactants. Therefore, a significant elevation of serum sialic acid is observed in inflammatory diseases, infectious diseases and neoplasms 1-3. The normal range of serum sialic acid was 45-72 mg/dl in the control survey. The "normal range" is still somewhat of a problem, as the values can differ from institution to institution 4. While serum sialic acid is known as a monitor of inflammation (e.g. in rheumatoid arthritis) 5, to the best of our knowledge there has been no report of its application for the monitoring of inflammatory bowel diseases. Under such circumstances, it was felt worthwhile to ascertain whether or not serum sialic acid could serve as a useful index of disease activity in Crohn's disease.
1. Comparison of serum sialic acid between patients with Crohn's disease and healthy subjects Subjects entered into this study were patients with Crohn's disease (groups A and B) and healthy volunteers. Group A patients (n=6) had no symptoms related to Crohn's disease, and their CRP was 0.0 mg/dl, although active ulcerations were evident on barium enema or small bowel examination. Group B patients (n=6) had undergone surgery for Crohn's disease, and were considered to be free of active ulcerations, based on small bowel examination and barium enema. Characteristics of patients and healthy subjects are shown in Table 1. 2. Correlation between serum sialic acid and CRP The subjects consisted of 13 patients with Crohn's disease of varying severity and symptomatology. In this study, attempts were made to correlate the serum sialic acid level with CRP only when the latter exceeded 1.0 mg/dl. The total n u m b e r of measurements was 28 in these 13 patients.
Received December 9, 1991. Accepted April 17, 1992. Address for correspondence: Rika Baba, M.D., Institute of Gastroenterology, Tokyo Women's Medical College, 8-1 Kawada-cyo, Shinjuku-ku, Tokyo 162, Japan.
October 1992
Serum sialic acid in Crohn's disease
605
Table 1. Characteristics of the patients with Crohn's disease and healthy subjects Age/sex
Disease location
Operation
Time after operation
Serum sialic acid
Serum albumin
70 72 87 61 64 64
4.1 +0.2 (g/all) 4.2 4.2 3.9 4.1 4.4 4.0
4yrs 4yrs 2yrs
60 47 49
4.3+0.3 (g/dl) 3.9 4.2 4.8
4mos lmos 8yrs
55 58 59
4.3 4.2 4.1
Crohn's disease (Group A) (n=6) (mean age=24.3+3.8) 22 M small intestine 22 F ileocolic 22 F ileocolic 27 M ileocolic 22 M ileocolic 31 M ileocolic Crohn's disease (Group B) (n=6) (mean age-----35.5+12.8) 51 M small intestine ileum resection 51 F ileocolic ileum resection 22 F ileocolic ileocecal resection anterior resection 22 M ileocolic ileocecal resection 29 M large intestine transverse colon resection 42 F ileocolic right hemicolectomy Healthy subjects (n---6) (mean age---32.3+4.7) sex (M:F)--4:2
3. Correlations between serum sialic acid and hemoglobin concentration(Hb), hematocrit(Hct), platelet count(Pit), retinol-binding protein (RBP), prealbumin(PA) and albumin(ALB) Seventeen asymptomatic patients with Crohn's disease were studied. They had no complaints and were overtly asymptomatic. Because of multiple measurements of serum sialic acid in the same patients, the total number of measurements does not equal the number of patients. Correlations were examined separately according to the level of CRP (upper: C R P < l . 0 m g / d l , lower: CRP: unlimited range). 4. Correlation between serum sialic acid and activity index of Crohn "sdisease (IOIBD: International Organization for the Study of Inflammatory Bowel Disease, CDAI: Crohn's Disease Activity Index) The subjects consisted of 7 patients hospitalized with Crohn's disease. The total number of measurements of IOIBD was 60, and that of CDAI was 35. 5. Statistical analysis The results were expressed as means and standard deviations. Statistical analysis was performed
4.7+0.4 (g/dl)
as follows: (a) One-way analysis of variance (ANOVA): Comparison of serum sialic acid levels between patients with Crohn's disease and healthy subjects. (b) Pearson's correlation coefficient Simple linear regression analysis: Correlation between sialic acid and CRP, Hb, Hct, Pit, RBP, PA and ALB. Serum sialic acid was measured by enzymatic assay using a reagent kit (Kyokutou Pharmaceutical Co. Ltd. Tokyo Japan). The method 6'7 for measurement is illustrated in Figure 1. CRP was measured by turbidimetric immunoassay (TIA), RBP was measured by single radial immunodiffusion (SRID), and prealbumin by nephelometry. Results
1. Comparison of serum sialic acid betweenpatients with Crohn's disease and healthy subjects The serum level of sialic acid was 50.3 + 4.4 mg/ dl in healthy subjects, 69.7+9.4 mg/dl in group A patients, and 54.7+5.5 mg/dl in group B patients (Figure 2). The serum sialic acid level of group A
R. Baba et aL
606
Vol. 27, N o . 5
neuraminidasr
Sialoglycoprotein (or sialoglycolipid)
H:O
'
N A N A + asialoglycoprotein (or asialoglycolipid) NANA-aldola.~
NANA
,
pyruvate + N-acetylmannosamine
Pyruvate + N A D H + H +
LDH
,
L-lactate + N A D § .
Figure 1. Enzymatic measurement of serum sialic acid. The a m o u n t of oxidized NADH measured by the change in a b s o r b a n c e at 3 3 9 nm is proportional to the amount of NANA (N-acetyl neuramic acid) present.
P
Gastroenterologia Japonica Copyright 9 1992 by The Japanese Society of Gastroenterology
Significance of serum sialic acid in patients with Crohn's disease Rika BABA, Kurato YASHIRO, Kou NAGASAKO, and Hiroshi OBATA Institute of Gastroenterology, Tokyo Women's Medical College, Tokyo, Japan Summary: Serum sialic acid was measured to evaluate the activity of Crohn's disease. The sialic acid levels of patients with Crohn's disease in remission (CRP 0.0 mg/dl) were significantly higher than those of healthy subjects and postoperative patients with Crohn's disease. In patients in remission, serum sialic acid was significantly correlated with hemoglobin, hematocrit, platelet, and rapid turnover protein. Correlations with platelet, retinol-binding protein, and prealbumin were especially strong. From these findings, it was concluded that serum sialic acid level provides a useful index of the activity of Crohn's disease. Gastroenterol Jpn 1992;27:604-610. Key words: Crohn's disease; platelet count; rapid turnover protein; serum sialic acid.
Introduction
Materials and Methods
In asymptomatic cases, the activity of Crohn's disease is difficult to estimate. Serum C-reactive protein (CRP) is too low to provide a useful index of the disease activity. However, the predictability of relapse is important in maintenance therapy. Sialic acid is included in acute phase reactants. Therefore, a significant elevation of serum sialic acid is observed in inflammatory diseases, infectious diseases and neoplasms 1-3. The normal range of serum sialic acid was 45-72 mg/dl in the control survey. The "normal range" is still somewhat of a problem, as the values can differ from institution to institution 4. While serum sialic acid is known as a monitor of inflammation (e.g. in rheumatoid arthritis) 5, to the best of our knowledge there has been no report of its application for the monitoring of inflammatory bowel diseases. Under such circumstances, it was felt worthwhile to ascertain whether or not serum sialic acid could serve as a useful index of disease activity in Crohn's disease.
1. Comparison of serum sialic acid between patients with Crohn's disease and healthy subjects Subjects entered into this study were patients with Crohn's disease (groups A and B) and healthy volunteers. Group A patients (n=6) had no symptoms related to Crohn's disease, and their CRP was 0.0 mg/dl, although active ulcerations were evident on barium enema or small bowel examination. Group B patients (n=6) had undergone surgery for Crohn's disease, and were considered to be free of active ulcerations, based on small bowel examination and barium enema. Characteristics of patients and healthy subjects are shown in Table 1. 2. Correlation between serum sialic acid and CRP The subjects consisted of 13 patients with Crohn's disease of varying severity and symptomatology. In this study, attempts were made to correlate the serum sialic acid level with CRP only when the latter exceeded 1.0 mg/dl. The total n u m b e r of measurements was 28 in these 13 patients.
Received December 9, 1991. Accepted April 17, 1992. Address for correspondence: Rika Baba, M.D., Institute of Gastroenterology, Tokyo Women's Medical College, 8-1 Kawada-cyo, Shinjuku-ku, Tokyo 162, Japan.
October 1992
Serum sialic acid in Crohn's disease
605
Table 1. Characteristics of the patients with Crohn's disease and healthy subjects Age/sex
Disease location
Operation
Time after operation
Serum sialic acid
Serum albumin
70 72 87 61 64 64
4.1 +0.2 (g/all) 4.2 4.2 3.9 4.1 4.4 4.0
4yrs 4yrs 2yrs
60 47 49
4.3+0.3 (g/dl) 3.9 4.2 4.8
4mos lmos 8yrs
55 58 59
4.3 4.2 4.1
Crohn's disease (Group A) (n=6) (mean age=24.3+3.8) 22 M small intestine 22 F ileocolic 22 F ileocolic 27 M ileocolic 22 M ileocolic 31 M ileocolic Crohn's disease (Group B) (n=6) (mean age-----35.5+12.8) 51 M small intestine ileum resection 51 F ileocolic ileum resection 22 F ileocolic ileocecal resection anterior resection 22 M ileocolic ileocecal resection 29 M large intestine transverse colon resection 42 F ileocolic right hemicolectomy Healthy subjects (n---6) (mean age---32.3+4.7) sex (M:F)--4:2
3. Correlations between serum sialic acid and hemoglobin concentration(Hb), hematocrit(Hct), platelet count(Pit), retinol-binding protein (RBP), prealbumin(PA) and albumin(ALB) Seventeen asymptomatic patients with Crohn's disease were studied. They had no complaints and were overtly asymptomatic. Because of multiple measurements of serum sialic acid in the same patients, the total number of measurements does not equal the number of patients. Correlations were examined separately according to the level of CRP (upper: C R P < l . 0 m g / d l , lower: CRP: unlimited range). 4. Correlation between serum sialic acid and activity index of Crohn "sdisease (IOIBD: International Organization for the Study of Inflammatory Bowel Disease, CDAI: Crohn's Disease Activity Index) The subjects consisted of 7 patients hospitalized with Crohn's disease. The total number of measurements of IOIBD was 60, and that of CDAI was 35. 5. Statistical analysis The results were expressed as means and standard deviations. Statistical analysis was performed
4.7+0.4 (g/dl)
as follows: (a) One-way analysis of variance (ANOVA): Comparison of serum sialic acid levels between patients with Crohn's disease and healthy subjects. (b) Pearson's correlation coefficient Simple linear regression analysis: Correlation between sialic acid and CRP, Hb, Hct, Pit, RBP, PA and ALB. Serum sialic acid was measured by enzymatic assay using a reagent kit (Kyokutou Pharmaceutical Co. Ltd. Tokyo Japan). The method 6'7 for measurement is illustrated in Figure 1. CRP was measured by turbidimetric immunoassay (TIA), RBP was measured by single radial immunodiffusion (SRID), and prealbumin by nephelometry. Results
1. Comparison of serum sialic acid betweenpatients with Crohn's disease and healthy subjects The serum level of sialic acid was 50.3 + 4.4 mg/ dl in healthy subjects, 69.7+9.4 mg/dl in group A patients, and 54.7+5.5 mg/dl in group B patients (Figure 2). The serum sialic acid level of group A
R. Baba et aL
606
Vol. 27, N o . 5
neuraminidasr
Sialoglycoprotein (or sialoglycolipid)
H:O
'
N A N A + asialoglycoprotein (or asialoglycolipid) NANA-aldola.~
NANA
,
pyruvate + N-acetylmannosamine
Pyruvate + N A D H + H +
LDH
,
L-lactate + N A D § .
Figure 1. Enzymatic measurement of serum sialic acid. The a m o u n t of oxidized NADH measured by the change in a b s o r b a n c e at 3 3 9 nm is proportional to the amount of NANA (N-acetyl neuramic acid) present.
P
