Gordan Lauc

Publications (101) View all

• Article: Heterozygous carriage of a dysfunctional Toll-like receptor 9 allele affects CpG oligonucleotide responses in B cells.

  Jelena Knezević, Dinko Pavlinić, William A Rose, Cynthia A Leifer, Kreso Bendelja, Jelka Gabrilovac, Marijo Parcina, Gordan Lauc, Andriy V Kubarenko, Branka Petricevic, Damir Vrbanec, Ljiljana Bulat-Kardum, Isabelle Bekeredjian-Ding, Jasminka Pavelić, Zlatko Dembić, Alexander N R Weber
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  ABSTRACT: Toll-like receptors (TLR) are employed by the innate immune system to detect microbial pathogens based on conserved microbial pathogen molecules. For example, TLR9 is a receptor for CpG-containing microbial DNA, and its activation results in the production of cytokines and type I interferons from human B cells and plasmacytoid dendritic cells, respectively. Both are required for mounting an efficient antibacterial or antiviral immune response. These effects are mimicked by synthetic CpG oligodeoxynucleotides (ODN). Although several hyporesponsive TLR9 variants have been reported, their functional relevance in human primary cells has not been addressed. Here we report a novel TLR9 allele, R892W, which is hyporesponsive to CpG ODN and acts as a dominant-negative in a cellular model system. The R892W variant is characterized by increased MyD88 binding and defective co-localization with CpG ODN. Whereas primary plasmacytoid dendritic cells isolated from a heterozygous R892W carrier responded normally to CpG by interferon-α production, carrier B cells showed impaired IL-6 and IL-10 production. This suggests that heterozygous carriage of a hyporesponsive TLR9 allele is not associated with complete loss of TLR9 function but that TLR9 signals elicited in different cell types are regulated differently in human primary cells.
  Journal of Biological Chemistry 05/2012; 287(29):24544-53. · 4.77 Impact Factor
• Source

  Available from: Maja Pucic Bakovic

  Article: Changes in plasma and IgG N-glycome during childhood and adolescence.

  Maja Pucic, Ana Muzinic, Mislav Novokmet, Marijana Skledar, Nela Pivac, Gordan Lauc, Olga Gornik
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  ABSTRACT: Despite the importance of protein glycosylation in all physiological and pathological processes and their potential as diagnostic markers and drug targets, the glycome of children is still unexplored. We analyzed N-linked plasma and IgG glycomes in 170 children and adolescents between 6 and 18 years of age. The results showed large biological variability at the population level as well as a large number of associations between different glycans and age. The plasma N-glycome of younger children was found to contain a larger proportion of large complex glycan structures (r = -0.71 for tetrasialylated glycans; r = -0.41 for trisialylated glycans) as well as an increase in disialylated biantennary structures (r = 0.55) with age. Core fucosylation and the level of agalactosylated plasma and IgG glycans decreased while digalactosylated glycans increased with age. This pattern of age-dependent changes in children differs from changes reported in adult population in both, direction and the intensity of changes. Also, sex differences are much smaller in children than in adults and are present mainly during puberty. These important observations should be accounted for when glycan-based diagnostic tests or therapeutics are being developed or evaluated.
  Glycobiology 03/2012; 22(7):975-82. · 3.58 Impact Factor
• Article: Distribution of Chlamydia trachomatis serotypes in clinical urogenital samples from north-eastern Croatia.

  Zinka Bošnjak, Snježana Džijan, Dinko Pavlinić, Magdalena Perić, Nataša Ružman, Ivana Roksandić Križan, Gordan Lauc, Arlen Antolović-Požgain, Jelena Burazin, Dubravka Vuković
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  ABSTRACT: The purpose of this study was to determine prevalence of Chlamydia trachomatis (Ct) urogenital infection and its serotype distribution from clinical samples in north-eastern Croatia. During a 3-year period, 2,379 urogenital samples were analyzed by real-time polymerase chain reaction (A group), while 4,846 genital swabs were analyzed by direct fluorescent antibody test (B group). 132 Ct positive specimens were genotyped by omp1 gene sequencing. The prevalence rate of Ct was 3.2 % in A and 1 % in B group. The most prevalent chlamydial genotype was E (44 %), followed by F (33 %), K (11.5 %), G (8 %), J/UW (5.3 %), D-IC (4.4 %), D-B120 (1.8 %), and B/IU, J/IU, Ia/IU (0.9 % each) serotypes. Single-nucleotide polymorphisms (SNPs) of omp1 gene were detected in E, K, and G serotypes. Some of these SNPs (C/T at position 272 and G/A at position 813 in E strain; C/T at position 884 in D strain) might represent novel omp1 variants.
  Current Microbiology 03/2012; 64(6):552-60. · 1.82 Impact Factor
• Source

  Available from: Jayesh Kattla

  Article: Association of medication with the human plasma N-glycome.

  Radka Saldova, Jennifer E Huffman, Barbara Adamczyk, Ana Mužinić, Jayesh J Kattla, Maja Pučić, Mislav Novokmet, Jodie L Abrahams, Caroline Hayward, Igor Rudan, Sarah H Wild, Alan F Wright, Ozren Polašek, Gordan Lauc, Harry Campbell, James F Wilson, Pauline M Rudd
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  ABSTRACT: Glycosylation is highly variable depending on many environmental factors. Using our fully quantitative high-throughput normal phase hydrophilic interaction liquid chromatography platform we have identified glycosylation changes associated with medication in the plasma N-glycome from three different population cohorts: ORCADES from the Orkney Islands in Scotland and CROATIA-Vis and CROATIA-Korcula from the Croatian islands of Vis and Korcula. Associations between glycosylation and the use of hormones (oral contraceptives, hormone replacement therapy), nonsteroidal anti-inflammatory drugs (aspirin and other NSAIDs), oral steroids (prednisolone) and steroid inhalers (beclomethasone) were investigated. Significant differences associated with usage of oral contraceptives were found with increased core-fucosylated biantennary glycans. Decreases in core-fucosylated biantennary glycans, core-fucosylated triantennary glycans with outer-arm fucose, and high mannosylated glycans were associated with the use of anti-inflammatory drugs. All of the changes in glycosylation were independent of blood group status. In conclusion, hormones and anti-inflammatory medication were associated with changes in glycosylation, possibly as a result of the modulatory effect of these drugs on the inflammatory response. In general, cancer is associated with inflammation, and many glycoproteins in the plasma are acute phase related to the host response. These preliminary data indicate the importance of correcting the levels of glycans used as biomarkers for the effects of medication.
  Journal of Proteome Research 03/2012; 11(3):1821-31. · 5.11 Impact Factor
• Article: Epigenetic silencing of HNF1A associates with changes in the composition of the human plasma N-glycome.

  Vlatka Zoldoš, Tomislav Horvat, Mislav Novokmet, Cyrille Cuenin, Ana Mužinić, Maja Pučić, Jennifer E Huffman, Olga Gornik, Ozren Polašek, Harry Campbell, Caroline Hayward, Alan F Wright, Igor Rudan, Katharine Owen, Mark I McCarthy, Zdenko Herceg, Gordan Lauc
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  ABSTRACT: Protein glycosylation is a ubiquitous modification that affects the structure and function of proteins. Our recent genome wide association study identified transcription factor HNF1A as an important regulator of plasma protein glycosylation. To evaluate the potential impact of epigenetic regulation of HNF1A on protein glycosylation we analyzed CpG methylation in 810 individuals. The association between methylation of four CpG sites and the composition of plasma and IgG glycomes was analyzed. Several statistically significant associations were observed between HNF1A methylation and plasma glycans, while there were no significant associations with IgG glycans. The most consistent association with HNF1A methylation was observed with the increase in the proportion of highly branched glycans in the plasma N-glycome. The hypothesis that inactivation of HNF1A promotes branching of glycans was supported by the analysis of plasma N-glycomes in 61 patients with inactivating mutations in HNF1A, where the increase in plasma glycan branching was also observed. This study represents the first demonstration of epigenetic regulation of plasma glycome composition, suggesting a potential mechanism by which epigenetic deregulation of the glycome may contribute to disease development.
  Epigenetics: official journal of the DNA Methylation Society 02/2012; 7(2):164-72. · 4.58 Impact Factor