Gyula Poór

Genetic Background of Anticyclic Citrullinated Peptide Autoantibody Production in Hungarian Patients with Rheumatoid Arthritis

Abstract:u2002 Polymorphisms of the peptidylarginine deiminase 4 (PADI4) gene encoding for the isoenzyme that converts arginyl into citrullyl residues have been shown to contribute to susceptibility to rheumatoid arthritis (RA), depending on the population studied. We aimed at determining whether PADI4 single nucleotide polymorphisms (SNPs) are associated with RA in a Hungarian population. The relationship between anticyclic citrullinated peptide (anti‐CCP) production and HLA‐DRB1 alleles encoding the shared epitope (SE) was also investigated. DNA samples were obtained from RA (n= 261) patients and from control donors (n= 120). HLA‐DRB1 genotyping was carried out by polymerase chain reaction (PCR) with sequence‐specific priming. PAD4_92 G/C and PAD4_104 T/C SNPs were genotyped using real‐time PCR allele discrimination. Autoantibodies against CCP were detected by ELISA. All healthy controls tested anti‐CCP negative, whereas 171 (66%) RA patients were anti‐CCP positive. No significant difference in allele or genotype frequencies were found between RA patients and controls for any of the PADI4 SNPs. Anti‐CCP seropositivity was unrelated to these two SNPs. No association was found between any of the PADI4 SNPs and HLA‐DRB1 subtypes. Presence of the HLA‐RB1 SE alleles was significantly associated with anti‐CCP seropositivity; HLA‐DRB1*0401 and HLA‐DRB1*1001 carriers showed the strongest association. In conclusion, our data suggest that polymorphisms of the PADI4 gene are not associated with rheumatoid arthritis and are unlikely to be responsible for the presence of anti‐CCP autoantibodies in a white Hungarian population. HLA‐DRB1 SE alleles, however, may significantly contribute to the genetic determination of anti‐CCP production in Hungarian patients with RA.

Gene Expression Profiling in Paget's Disease of Bone: Upregulation of Interferon Signaling Pathways in Pagetic Monocytes and Lymphocytes†‡§

We examined the gene expression profile of genes involved in bone metabolism in 23 patients with PD compared with 23 healthy controls. We found a significant overexpression of the genes of the IFN pathway along with a downregulation of tnf‐α. Our result suggest that IFN‐mediated signaling may play important roles in aberrant osteoclastogenesis of PD.

Detection of TT Virus in Patients with Idiopathic Inflammatory Myopathies

Abstract: The TT virus, a recently identified single‐stranded DNA virus with unknown pathogenicity, has been shown to commonly infect humans. Viruses have been considered to contribute to disease pathogenesis in autoimmune disorders including idiopathic inflammatory myopathies (IIMs) and rheumatoid arthritis (RA). We assessed the prevalence of TTV infection in IIM compared with that in patients with RA and healthy blood donors. Detection of TTV was conducted by nested PCR and real‐time PCR in the sera of 94 patients with IIM, 95 RA patients. and 95 age‐ and sex‐matched healthy blood donors. Identity of the PCR products was confirmed by sequencing. TTV DNA was detected in 61 of 94 (64.9%) patients with IIM, in 64 of 95 (67.4%) patients with RA, and in 62 of 95 (65.3%; P > 0.05) healthy individuals. Age, sex, activity, or duration of disease had no influence on TTV positivity in either group. However, patients with severe IIM (n= 36) had a significantly higher rate of TTV infection (31/36, 86.1%) than patients with mild disease (30/58, 51.7%, P < 0.05, χ2= 10.0). Disease was considered severe in IIM when immunosuppressive treatment was necessary because of continuous high activity and/or serious inner‐organ involvement despite corticosteroid treatment. In conclusion, although we found the detection rate of TTV similar in patients with idiopathic inflammatory myopathies and rheumatoid arthritis and comparable to that in healthy controls, our data suggest that infection with TT virus may result in a more severe disease in patients with idiopathic inflammatory myopathies.

Prevalence of obesity in an elderly Hungarian population

Background: There are few cross-sectional population-based studies on obesity in Hungary. Aim of this study was to characterize the prevalence, associated diseases and metabolic laboratory parameters for obesity in men and women in Budapest, Hungary. Methods: A random sample of 641 persons (307 males and 334 females) aged 50 years and over were recruited from a population register in Budapest. Subjects were interviewed, had height and weight measured in standard fashion. Those who were obese (BMI > 30.0 kg/m2) were matched individually with non-obese subjects. Altogether 101 pairs (48 women and 53 men pairs) were taking part and these subjects had blood taken for amount of serum glucose, lipids and uric acid. Results: The mean age of men and women was 65.0 (SD = 9.1) years and 64.6 (SD = 8.9) years, respectively. The prevalence of obesity was 18.1% in men and 15.4% in women (p < 0.05). In both sexes the mean body mass index was higher at age of 50–64 years than at older ages [in men 27.2 (SD = 3.7) kg/m2 vs. 26.7 (SD = 3.3) kg/m2, p = 0.286 and in women 26.7 (SD = 4.2) kg/m2 vs. 25.4 (SD = 4.0) kg/m2, p = 0.005]. Body mass index was higher in men than in women at all ages. In the case–control study the mean age of obese and non-obese individuals were 63.1 (SD = 7.8) years and 63.2 (SD = 7.9) years, respectively. Obesity was significantly associated with a history of diabetes mellitus (18 vs. 7%, p < 0.05) and hypertension (48 vs. 28%, p < 0.05). Compared to the non-obese, those who were obese had a higher level of serum uric acid (311 ± 102 vs. 280 ± 96μmol/l, p < 0.05) and triglyceride (2.67± 1.95 vs. 1.86 ± 0.95 mmol/l, p < 0.05). Conclusion: The high prevalence of obesity both in elderly men and women and its strong association with chronic diseases causes economical and social burden for Hungary. Strategies and programs for weight maintenance as well as weight reduction must become a higher public health priority.

Altered expression of Fcγ and complement receptors on b cells in systemic lupus erythematosus

Abstract:u2002 Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by B cell hyper‐reactivity, autoantibody production, immune complex (IC) deposition, and multiple organ damage. The contribution of IC and B cell–mediated changes in the pathogenesis of SLE is well established, however, the exact role of IC‐binding receptors expressed on B cells, Fcγ receptors, and complement receptors CR1 and CR2 in these pathological processes is unclear. Development of lupus‐like symptoms in mice defective for the inhibitory FcγRIIb and genetic association of certain FcγR genes with SLE demonstrate a significant role for these receptors but reports indicating alterations of Fcγ or complement receptor‐mediated B cell functions in human SLE are relatively few. The present review highlights a selected set of data including our own discussing the significance of animal models, genetics, and functional alterations of these IC‐binding receptors in the etiopathogenesis of SLE.

Multiplex site-directed mutagenesis strategy including high-efficiency selection of the mutant PCR products

Site-directed mutagenesis is of great importance for probing the structure/function relationship of proteins. Developing our previous method (Nagy etxa0al. Anal Biochem 324:301–303, 2004), here we report a multiplex strategy for site-directed mutagenesis using PCR in one tube to introduce a single mutation into three or more genes at the same time. DNA fragments carrying the desired mutation can be distinguished from each other in a standard antibiotic selection step of the transformed bacteria. Due to this strategy the mutagenesis procedure for several genes can be accelerated.