Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) genotypes in colorectal cancer.

Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) are key factors of the lectin pathway of complement activation. Polymorphisms of the MBL2 and MASP-2 genes affect serum levels of MBL and MASP-2. In patients with colorectal cancer (CRC), the MBL and MASP-2 serum levels are increased and high MASP-2 levels are associated with recurrence and poor survival, whereas low MBL levels predict post-operative pneumonia. It is not known whether these associations are genetically based. In this study, the MBL and MASP-2 genotypes are investigated in 593 patients with CRC and 348 healthy controls. The potential association between genetic profile and infections, recurrence and survival is evaluated. Four single-nucleotide polymorphisms (SNPs) of MBL2 were analysed using TaqMan assays, with characterization of MBL2 wildtype A, variants B, C and D and alleles H/L, Y/X and P/Q. The SNP D120G for MASP-2 was determined. Serum levels of MBL and MASP-2 were measured. The MBL2 and MASP-2 genotype distribution was similar among patients with CRC and healthy controls and MBL2 genotype significantly associated with MBL concentration in serum (P<0.0001). No significant association between MBL2/MASP-2 genotype and post-operative infectious complications (P=0.33 and 0.22), recurrent cancer or survival (P=0.74 and P=0.61 respectively) was found. Thus, the increased serum levels of MBL and MASP-2 found in patients with CRC are not explained for by genetic profiles. In contrast to what has been demonstrated for serum levels of MBL and MASP-2, the genotypes do not predict disease course of the CRC patients.

Biological variation in circulating levels of mannan-binding lectin (MBL) and MBL-associated serine protease-2 and the influence of age, gender and physical exercise.

Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) are central components of the MBL pathway of complement activation, and may have potential as clinical biomarkers in colorectal cancer (CRC). Prior to clinical usage, knowledge of the biological variations of the molecules is needed. We here investigate variations of MBL and MASP-2 in healthy persons over time and in relation to gender, age and physical activity. MBL and MASP-2 concentrations were determined in serum from healthy adults over a 3-week period and this was repeated 6 months later (n = 32); during a 24-h period (n = 16); and in relation to physical exercise (n = 14). Concentrations in serum and plasma were compared (n = 198). No significant variation over 6 months and no circadian variation was found for MBL (P = 0.39 and P = 0.34 respectively) or MASP-2 (P = 0.54 and P = 0.55). Physical exercise did not affect the levels (P > 0.8). Serum and plasma levels were only marginally different, and were independent of age and gender. Circulating levels of MBL and MASP-2 are stable over time in healthy individuals, which is advantageous for their potential application as biomarkers.

Influence of major surgery on the mannan-binding lectin pathway of innate immunity.

The mannan-binding lectin (MBL) pathway of complement activation is important in host defence against pathogens and possibly against cancer. We investigated the effect of major surgery on two central components of the MBL pathway; MBL and the MBL-associated serine protease MASP-2, and for comparison also measured the interleukin (IL)-6 and C-reactive protein (CRP) levels. Serial blood samples were obtained from patients belonging to two different cohorts. Cohort 1 comprised 60 patients undergoing open or laparoscopic colectomy for benign disease (n = 12) or colon cancer (n = 48). Cohort 2 comprised 27 patients undergoing elective, open surgery for colorectal cancer, and was included in order to cover blood sampling between days 2 and 6. As expected, the surgical stress induced a marked acute phase response, as evidenced by a large increase in IL-6 (18-fold) and CRP (13-fold) levels with maximum at 12 h and 2 days, respectively. However, in both cohorts the levels of MBL and MBL-associated serine protease 2 (MASP-2) were largely unaffected, except for a minor but significant increase around day 8 in cohort 1. The preoperative levels of IL-6 and CRP were correlated significantly in both cohorts (r = 0.71, P < 0.0001 and r = 0.65, P = 0.005, respectively). Preoperative MASP-2 correlated with preoperative CRP (r = 0.59, P = 0.001) and IL-6 (r = 0.55, P = 0.02) in cohort 2 only. In contrast to the marked effects on the levels of IL-6 and CRP, the surgery influenced only marginally the two proteins of the MBL pathway.

Increased activity of the mannan-binding lectin complement activation pathway in patients with colorectal cancer.

BACKGROUND: Postoperative bacterial infectious complications are frequent in patients with colorectal cancer (CRC), with subsequent increased recurrence rates and poor prognosis. Deficiency of the mannan-binding lectin (MBL) complement activation pathway may cause increased risk of infection in certain patient groups. It is hypothesized that a deficient MBL pathway might be more frequent among patients with CRC than in healthy individuals. The MBL pathway was therefore evaluated in serum obtained preoperatively from 193 patients with primary CRC and in serum from 150 healthy volunteers. METHODS: Serum MBL concentrations and MBL/MASP activity were determined using immunofluorometric assays. The levels are presented as the median, inter-quartile range and range. RESULTS: Serum MBL levels were significantly (P < 0.0002) increased in patients with colorectal cancer (1384 (400-2188) ng/mL) (median, inter-quartile range) compared with levels in healthy blood donors (924 (230-1476) ng/mL). Similarly, the MBL/MASP activity was significantly (P < 0.0002) increased in patients (584 (202-914) mU/mL) compared with in blood donors (319 (0-684) mU/mL). This was independent of age, gender, tumour location in the colon or rectum, and disease stages according to Dukes' classification. No statistical difference (P=0.20) in frequency of MBL deficiency was found between the patients (20%) and the donors (27%). CONCLUSIONS: Overall, the MBL complement activation pathway is significantly increased in patients with colorectal cancer compared with healthy persons. However, similar frequencies of MBL pathway deficiency are observed in patients and healthy persons.

Postural balance and its sensory-motor correlates in 75-year-old men and women: a cross-national comparative study.

BACKGROUND: There are no earlier cross-national comparative studies analyzing the functions of the posture control mechanisms and its sensory-motor correlates in elderly subjects. We investigated whether there are differences in balance between elderly subjects living in different geographical areas, and analyzed the sensory-motor associates of balance in men and women separately. METHOD: Using a force platform method, the functioning of the posture control system under three standardized conditions (normal standing, eyes open; normal standing, eyes closed; and tandem standing, eyes open) was studied among samples of 75-year-old residents in three Nordic localities, namely Glostrup in Denmark, Göteborg in Sweden, and Jyväskylä in Finland. The associations of the variables describing performance in each test with other sensory and motor functions were studied using correlation analyses and multivariate regression models. RESULTS: Differences between the populations were observed in both tests with visual control, favoring the participants from Glostrup and Jyväskylä compared with those from Göteborg. However, only minor differences between the subjects from different localities were observed in the test performed with the eyes closed. In all localities there was a primary sex difference in favor of the women which, however, mainly disappeared when body height was taken into the analyses as a covariate. A good performance in the balance tests (body height-adjusted values) was associated with good visual acuity, low vibrotactile thresholds, and high psychomotor speed. Also, isometric muscle strength, especially hand grip and body extension, was positively associated with good performance in the balance tests. Among the women, a poorer balance was observed in women with a smaller body mass. The results of the multivariate analyses showed that among the men, the most important predictors of good performance in the balance tests were low vibrotactile threshold on the foot, high isometric hand grip strength, and low body stature. Among the women, the most important predictors were low body stature, high body mass, high isometric body extension strength, and high psychomotor speed. However, only a small proportion of the variance in balance (about 13% in the men and 11% in the women) could be explained by the help of these factors. CONCLUSIONS: As the same procedure was applied to the analysis of postural balance, some differences between the populations living in different localities could be detected in some of the tests. The better performance of the women in the balance tests may partly be explained by anthropometric factors, especially differences in body height. There may also be differences in sensory-motor associates of balance in elderly men and women. On the basis of the associations observed, it is difficult to explain the differences in balance between the sexes or subjects living in different localities. Within the sexes, only a small proportion (10-13%) of the variation in balance during normal standing with eyes open could be explained by the factors included in the study.