Irakli Jaliashvili

Statens Serum Institut, København, Capital Region, Denmark

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Publications (8)29.29 Total impact

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    ABSTRACT: 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. 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. 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. These results indicate that TN may play a role in neurological diseases and may serve as a diagnostic aid in MS.
    No preview · Article · Feb 2006 · Scandinavian Journal of Clinical and Laboratory Investigation
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    ABSTRACT: Tetranectin (TN) is a 67 kDa glycoprotein thought to play a prominent role in the regulation of proteolytic processes via its binding to plasminogen and indirect activation of plasminogen. The TN concentration in serum is approximately 10 mg/l and is reduced in patients with several cancers. The TN concentration in the normal CSF has not been examined. The TN concentration in the serum and CSF of 47 normal subjects without neurological disorders was established using a polyclonal sandwich ELISA. The median TN concentration (quartile range) was 10.8 mg/l (9.0-12.1) in serum and 0.43 mg/l (0.3-0.53) in CSF. The TN index median (quartile range), defined as (TN CSF concentration/TN serum concentration)/(Albumin CSF concentration/Albumin serum concentration), was found to be 5.5 (4.7-7.6), suggesting intrathecal synthesis or selective uptake of TN in CNS. Immunohistochemistry showed TN immunoreactivity in neurons and dendrites, but no staining in glial cells in the cerebrum and cerebellum. In plexus choroideus, the ependymal cells exhibited strong immunoreactivity. TN in serum and CSF were immunochemically identical and of similar size. TN is present in normal brain and CSF, and the TN index is very high, but further studies are necessary to decide whether TN is synthesised in the CNS or selectively transported over the blood-brain barrier.
    No preview · Article · Oct 2005 · Clinica Chimica Acta
  • M Christiansen · I Jaliashvili
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    ABSTRACT: Pregnancy-associated plasma protein A (PAPP-A) is a maternal serum marker of fetal chromosomal disease and a risk marker for adverse outcome. PAPP-A in the circulation exists both as a 2:2 complex (PAPP-A/proMBP) with the proform of eosinophil major basic protein (proMBP) and as dimeric PAPP-A. Non-PAPP-A containing proMBP complexes constitute the bulk of proMBP in maternal serum. We developed and characterized a sandwich enzyme immunoassay for PAPP-A using a polyclonal rabbit anti-PAPP-A/proMBP antibody (SSI 6823) and a monoclonal murine anti-PAPP-A/proMBP antibody (HYB 234-3), reactive with the PAPP-A part of PAPP-A/proMBP. The assay range was 2 mIU/L-500 mIU/L, intra- and inter-assay coefficients of variation <10%. The immunoreactivity eluted ahead of thyroglobulin, Mr 669 kDa, in gel filtration and bound to a heparin column. Serum concentrations of PAPP-A were determined in gestational weeks 5-13 in 167 pregnant women with normal fetuses and 39 women with Down's syndrome (DS) fetuses. The median PAPP-A MoM (multiples of the median in normal controls) in DS pregnancies was 0.30 (quartile range: 0.17-0.54). The PAPP-A logMoMs in DS pregnancies were normally distributed with a mean of -0.5927 and SD of 0.3639. When simulating the performance of PAPP-A and age as markers for DS in population screening a detection rate (DR) of 62% was found for a screen positive rate (SPR) of 5%. Together with beta-HCG and nuchal translucency, two other first trimester markers for fetal DS, a DR 90% could be obtained for an SPR of 5%.
    No preview · Article · Oct 2003 · Scandinavian Journal of Clinical and Laboratory Investigation
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    ABSTRACT: To screen for congenital toxoplasmosis, we developed a time-resolved immunofluorometric assay for the simultaneous detection of Toxoplasma gondii-specific IgM and IgA in filter-paper samples collected from newborns 4-7 days after birth. The assay was performed on the AutoDELFIA, and results were calculated based on the ToxoM WHO Third International Reference Serum. Comparison with an in-house mu-capture immunoassay was carried out retrospectively on filter-paper samples from children with confirmed congenital toxoplasmosis. Prospectively the assay was compared with a mu-capture immunoassay on 68 394 samples and a commercially available assay on another 69,467 samples. Before serum was requested from the newborn, positive samples were tested for IgA and IgM separately and in an IgM-immunosorbent agglutination assay developed for filter-paper samples. Intra- and interassay variations (CVs) were 8% and 16%, respectively. The cutoff of 5 units/mL produced a 0.5% retest rate. The assay detected 13 of 18 (72%) samples from newborns diagnosed with congenital toxoplasmosis in the retrospective study. Prospectively, the assay identified 24 newborns who were later diagnosed with congenital toxoplasmosis. Results for all 24 cases were positive by the respective comparison method. No cases were detected solely by the IgA antibodies in the sample. Neonatal screening for congenital toxoplasmosis can be automated by use of purified europium-labeled antigen for detection of T. gondii-specific IgM and IgA eluted from filter-paper samples.
    Full-text · Article · Dec 2002 · Clinical Chemistry
  • Annemette V. Thougaard · Irakli Jaliashvili · Michael Christiansen
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    ABSTRACT: 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 Mr 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 Mr 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.
    No preview · Article · May 2001 · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology
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    ABSTRACT: The proform of eosinophil major basic protein (ProMBP) exists in serum from pregnant women complexed with a variable fraction of angiotensinogen (Ang). A subfraction further binds complement C3dg in a 2:2:2 complex. The function, physiology, and clinical importance of ProMBP complexes are unknown, and the specific quantification of these complexes has not been possible. We developed an ELISA for the ProMBP/Ang complexes, using a monoclonal antibody against ProMBP for capture and a chicken anti-human Ang antiserum for detection. Calibrators were standardized with WHO IRP 78/610 for pregnancy proteins in the assay range 0.95-15.6 mIU/L. The concentrations of ProMBP/Ang complexes in serum of nonpregnant blood donors (n = 79) were log-normally distributed with a central 95th interval of 985-3655 mIU/L. In pregnancy, mean serum concentrations were increased from week 7, and the concentrations reached term concentrations in week 18. ProMBP/Ang complexes eluted in gel filtration as a broad peak with a molecular mass of approximately 230 kDa. The concentration of ProMBP/Ang/C3dg increased during blood coagulation, suggesting that the ProMBP/Ang/C3dg complex may be a marker of complement activation. ProMBP/Ang complexes are present in serum from nonpregnant persons as well as pregnant women, and the direct assays described here will make it possible to study the biochemistry and the clinical significance of different ProMBP complexes in pathological conditions and pregnancy.
    No preview · Article · Sep 2000 · Clinical Chemistry
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    ABSTRACT: 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 μg/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.
    No preview · Article · Aug 1998 · Clinica Chimica Acta
  • Finn Sellebjerg · Irakli Jaliashvili · Michael Christiansen · Peter Garred
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    ABSTRACT: The pathogenesis of multiple sclerosis (MS) appears to involve autoimmune phenomena in the central nervous system. Activation of the complement system is suggested to be involved in the pathogenesis. Cerebrospinal fluid (CSF) and plasma samples from 65 patients with acute optic neuritis (ON) as a possible first symptom of MS (n=18), ON (n=16) or other attacks of clinically definite MS (n=15), and neurological control subjects (n=16) were studied. Activation of the initial part of the complement activation cascade was assessed by measuring activation of the C3 molecule; terminal activation of the complement cascade was assessed by measuring the terminal complement complex (TCC). Demyelination was estimated by the CSF concentration of myelin basic protein and neurological disability was assessed with the Kurtzke expanded disability status scale (EDSS) score. Activation of the initial part of the complement activation cascade occurred in each of the three groups of patients with demyelinating disease, but was not correlated to demyelination or disability. Increased concentrations of TCC were detected in patients with attacks of MS other than ON. The CSF concentrations of TCC, myelin basic protein (MBP) and neurological disability correlated significantly. The strongest correlation was between neurological disability and the CSF concentration of TCC (r=0.55, P=0.003). Full activation of the complement cascade during attacks of MS may be restricted to patients with more advanced disease and is significantly correlated to the degree of neurological disability. This suggests that specific treatment with agents that inhibit complement activation may interfere with mechanisms involved in the pathogenesis of neurological disability in patients with MS.
    No preview · Article · Jun 1998 · Journal of the Neurological Sciences