Tetranectin in cerebrospinal fluid of patients with multiple sclerosis.

OBJECTIVE: Tetranectin (TN) is a glycoprotein and C-type lectin thought to play a prominent role in tissue remodelling. The aim of this study was to determine the TN serum and cerebrospinal fluid (CSF) concentration in patients with multiple sclerosis (MS) and controls. MATERIAL AND METHODS: Two-hundred-and-four patients, divided into four diagnostic groups, i.e. definite MS (n = 76), possible onset symptoms of MS (n = 48), other non-inflammatory neurological diseases (n = 61) and other inflammatory neurological diseases (n = 19) and 47 controls with no history of neurological disease were analysed for TN in serum and CSF using a polyclonal sandwich ELISA. RESULTS: All tested groups, e.g. definite MS, possible onset symptoms of MS, other neurological disease, both inflammatory and non-inflammatory, had decreased concentrations of TN in the CSF compared to the concentrations in controls. The quotient of TN in CSF divided by the concentration in serum (QTN) correlated significantly with the same quotient of albumin (QALB), was significantly correlated with the same quotient of albumin QALB. To account for differences in blood brain barrier permeability, we calculated a TN-index defined as: TN-index = QTN/QALB. QTN was significantly decreased in all groups compared to that in controls. However, in definite MS and patients with first attack of MS, the TN-index was not significantly different from that of controls. In contrast, other neurological diseases, both inflammatory and non-inflammatory, were associated with a decreased TN-index. CONCLUSION: These results indicate that TN may play a role in neurological diseases and may serve as a diagnostic aid in MS.

Tetranectin-like protein in vertebrate serum: a comparative immunochemical analysis.

The glycoprotein tetranectin (TN) found in human serum is a 90-kDa homotrimeric C-type lectin binding Ca2+, heparin and plasminogen kringle 4. TN is suggested as being implicated in tissue remodelling. The antigenic reactivity of putative TN was examined in serum from 14 different animal species using three sandwich enzyme immunoassays for human TN. Crab-eating macaque serum showed the strongest reaction, followed by horse and cat. Serum from cow, goat, pig, mouse and chicken reacted weakly, while dog, trout, and the amphibian and the reptile species did not react. The TN-like protein from macaque, horse and cat serum bound heparin and showed the same dependence on Ca2+ for interaction with the monoclonal antibodies as human TN. Gel filtration of sera from the three animal species showed that the TN-like protein eluted as single peaks with a M(r) of 70-90 kDa. Western blotting of horse and cat TN-like protein electrophoresed under reducing conditions showed that the antibodies against human TN reacted with a single band with an approximate M(r) of 30 kDa, indicating that the TN-like protein is also a homotrimer. Horse and cat TN-like protein interacted with human kringle 4-sepharose. Most likely, the reacting protein represents crab-eating macaque, horse and cat homologues of human TN.

Correlation between alpha 1-acid glycoprotein and total sialic acid in serum from dogs with tumours.

The influence of the acute phase protein alpha 1-acid glycoprotein (AGP) on the concentration of total sialic acid (TSA) in serum was investigated by assessing their degree of correlation in 115 clinically healthy dogs, 29 dogs with malignant mammary tumours, 12 dogs with various other malignant tumours, 12 dogs with benign mammary tumours and 10 dogs with various other benign tumours. Serum from dogs with malignant mammary tumours and other malignant tumours had a statistically significant correlation between AGP and TSA concentrations (Spearman correlation coefficient (rS) = 0.52, P = 0.0005, n = 41). The correlation was also statistically significant in dogs with benign mammary tumours and other benign tumours (rS = 0.48, P = 0.02, n = 22). The Spearman correlation coefficient was 0.51 (P = 0.0001, n = 63) in all dogs with tumours. This was also the case if only those dogs with levels of AGP comparable to healthy dogs (< 750 mg/l) were included in the analysis (rS = 0.42, P = 0.01, n = 56). In clinically healthy dogs, the correlation was not statistically significant (rS = 0.17, P = 0.07, n = 115). None of the four groups of dogs with tumours had changed serum AGP concentrations compared to clinically healthy dogs (all t-tests gave P values above 0.05). The serum concentrations of AGP did not correlate with the clinical stage of dogs with mammary tumours. In conclusion, AGP and TSA concentrations in serum are positively correlated in dogs with tumours, partially explaining the increase in serum TSA in these dogs. Increased sialylation of the AGP molecule in dogs with tumours might contribute to the increased serum TSA levels.

Total serum sialic acid is a general disease marker rather than a specific tumour marker in dogs.

The aim of the present study was to examine the levels of total sialic acid (TSA) in serum of clinically healthy dogs and dogs with various diseases to evaluate the usefulness of TSA as a tumour marker. TSA levels in clinically healthy dogs were not different between sexes, but pregnant and lactating dogs had higher mean (+/- standard deviation (SD)) TSA levels than clinically healthy female dogs (642 +/- 78 vs. 495 +/- 73 mg/l, P < 0.001). Eighty-eight dogs with different tumours (54 malignant and 34 benign tumours of different tissues) had higher mean TSA levels than 148 clinically healthy dogs (675 +/- 143 vs. 498 +/- 75 mg/l, P < 0.01). Fifty dogs with other diseases excluding tumours (skin, urinary system, and gastrointestinal diseases, pyometra, other inflammatory diseases, and Cushing's syndrome) had slightly higher TSA levels than the tumour-bearing dogs (730 +/- 159 mg/l, P = 0.02). TSA levels in dogs with malignant tumours did not differ from dogs with benign tumours (682 +/- 144 vs. 664 +/- 142 mg/l, P = 0.73). A receiver-operating characteristic (ROC) plot revealed a maximum sensitivity and specificity combination of 69% and 91% (TSA cut-off concentration 595 mg/l) in distinguishing between healthy dogs and dogs with tumours. When evaluating TSA measurements to distinguish dogs with other diseases from dogs with tumours, a maximum sensitivity and specificity combination of 50% and 75% was found (cut-off concentration 761 mg/l). WHO staging of mammary tumours revealed an increase in TSA levels with increasing stage (P < 0.0001, rs, = 0.62). In conclusion, the nonspecificity of increases makes TSA determinations unsuitable as a tumour marker. TSA levels seem instead to be a general disease marker. Whether serial TSA measurements could be used in the follow-up of dogs operated for malignant tumours should be further investigated.

Determination of serum tetranectin: technical and clinical evaluation of three sandwich immunoassays.

The performance of two sandwich-type immunoassays for the determination of the tumour marker tetranectin using monoclonal antibodies Hyb 130-13 and 130-14 as catching layer was compared with the performance of a polyclonal assay. Sensitivities were 0.4-0.6 microg/l, and intra- and inter-assay coefficients of variation were < 10% in all assays. One-hundred-and-ten blood donors were examined, and women had higher concentrations of tetranectin in serum than men when measured with monoclonal assays (P < 0.05). In preoperative serum samples from 43 patients with ovarian cancer, tetranectin concentrations were reduced (P < 0.001), and the mean tetranectin concentration decreased with increasing FIGO stage of the patients (P < 0.05). In sera from patients with ovarian cancer, tetranectin concentrations were lower in the polyclonal assay than in the monoclonal assays. This could, hypothetically, be explained by ligand-binding or other conformational changes in tetranectin, influencing the antigenicity of the molecule.

Evaluation of an automated spectrophotometric assay for the determination of total sialic acid in canine serum.

This study validates an automated enzymatic assay using the Cobas Fara (Roche) centrifugal analyser, which offers a reliable measurement of the total sialic acid concentration in canine serum as assessed by evaluating the precision and accuracy. Data are presented on the biological variation in the total serum sialic acid concentration. Measurements of total serum sialic acid concentration appear to be useful in distinguishing dogs with neoplastic disorders from clinically healthy dogs.