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Specific IgA, IgG, and IgE antibodies to food antigens in 35 participants with autistic disorder and 21 of their siblings in the Republic of Macedonia were examined. Statistically significant higher plasma concentration of IgA antibodies against alpha-lactalbumin, beta-lactoglobulin, casein, and gliadin were found in the children with autistic disorder. Plasma concentrations of IgG antibodies against alpha-lactalbumin, beta-lactoglobulin, and casein in participants with autistic disorder were significantly higher. IgE-specific antibodies (alpha-lactalbumin, beta-lactoglobulin, casein, and gluten), as well as plasma concentration of total IgE, also were statistically significantly higher in the participants with autistic disorder. Gender differences were found for select IgA, IgG, and IgE (but not for total IgE) food-specific antibodies (kU/L) in the participants with autistic disorder and their siblings. (Contains 6 tables.)

The aim of our research was to examine changes in the immune system of the rats influenced by the elevated ambient temperature. Male Wistar rats were divided, into 2 groups and housed at 20 ± 2°C (n=64, control group) and 35 ± 1°C (n=74, experimental group), during precise timing of 1, 4, 7, 14, 21, and 30 days. All the animals were given food and water ad libitum, and were lighted during 12 hours per day. We have measured IgG, IgG1, IgG2a, IgG2b and IgG2c. The obtained results showed significant elevation in the level of IgG after 4 and 7 days (+32%), IgG2a after 7th (+88%), 14th and 21nd day (+110%), IgG2b after 14 days (+60%) at 35 ± 1°C compared with the control group at 20 ± 2°C. IgG1 level was not affected and IgG2c showed significant decrease after 21st day at 35 ± 1°C. In conclusion, during the elevated ambient temperature the immune system is activated as one of the regulation mechanisms in homeostasis and survival of the population.

Approximately 10 years after vaccination with the recombinant zoster vaccine (RZV), an interim analysis of this follow-up study of the ZOE-50/70 trials demonstrated that efficacy against herpes zoster remained high. Moreover, the safety profile remained clinically acceptable, suggesting that the clinical benefit of the RZV in ≥50-year-olds is sustained up to 10 years. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the association of 22 cytokine gene polymorphism in Macedonians with chronic obstructive pulmonary disease (COPD). The sample of the population comprised of 301 normal respondents and 62 patients with COPD. Cytokine genotyping was performed by polymerase chain reaction with sequence-specific priming (PCR-SSP). Positive (susceptible) association was found between patient with COPD and IL-1α -889/C allele; where as negative (protective) association among was found for the following alleles IL-1β +3962/C; IL-12B -1188/A; IFNγ +874/T; IL-2 -330/G; IL-4 -1098/G and IL-4-33/C. We found positive (susceptible) association between patients with COPD and following genotypes: IL4 -33/T:T; IFNγ +874/A:A; IL-4 -1098/T:T ; IL-1α -889/C:C; IL-1β +3962/C:T; IL-12B -1188/C:C; IL-4Rα +1902/G:G; IL-10 -1082/G:G; IL-2 -330/T:T; IL-4 -590/C:C; and IL-1α -889/C:T. Negative (protective) association between patients with COPD and following genotypes was found: IFNγ +874/A:T; IL-4 -33/C:T; IL-4 -1098/G:T; IL-2 -330/G:T; IL-1β +3962/C:T; IL-4 -590/C:T; IL-10 -1082/A:G; and IL-4 -33/C:C. Positive (susceptible) association between patients with COPD and following haplotypes was found: IL-4/TCT; IL-10/ATC; and IL-2/TG, and negative (protective) association was found between the patients with COPD and haplotypes for: IL-4/TTC; and IL-4/GCC. It could be concluded that several cytokine polymorphisms are positively (susceptible), or negatively (protective) associated with COPD in Macedonians.

Bronchial asthma is a multifactorial disease whereby both environmental and genetic factors contribute to its aetiology and/or clinical severity. The aim of this study was to examine the association of 22 cytokine gene polymorphism in the Macedonian population with bronchial asthma (BA). The sample of the population comprised of 301 normal unrelated individuals and 74 patients with BA. Cytokine genotyping was performed by PCR. Susceptible cytokine polymorphisms for BA for ten genotypes (IL-4 -1098/T:T, TNF-α -238/A:G, IL-4 -590/C:C, IL-2 +166/T:T, IL-2 -330/T:T, IL-10 -1082/G:G, IFNγ utr5644/T:T, IL-10 -1082/A:A, IL-1β +3962/T:T, IL-6 -174/G:G), six diplotypes, four haplotypes, and two alleles were found. Protective cytokine polymorphisms for BA for seven cytokine genotypes (IL-4 -1098/G:T, TNF- α -238/G:G, IL-2 -330/G:T, IL-4 -590/C:T, IFNγ utr5644/A:T, IL-1β +3962/C:T, IL-10 -1082/A:G), six cytokine diplotypes, four cytokine haplotypes, and four cytokine alleles were found. We concluded that several cytokine polymorphisms are protective, or susceptible associated with BA in population of Macedonians.

배경: The recombinant zoster vaccine (RZV) has demonstrated high vaccine efficacy (VE) against herpes zoster (HZ) in adults ≥50 years of age (YOA) in 2 phase 3 clinical trials (ZOE-50, NCT01165177; ZOE 70, NCT01165229). VE persisted up to year (Y)2 in the interim analysis of the extension study (ZOSTER-049, NCT02723773). Here, we describe the interim analysis for Y4 of the extension study. Understanding VE persistence and long-term protection against HZ can help optimize RZV use in adults ≥50 YOA. 방법: The study design is detailed in Fig. 1. Primary objective included VE against HZ during ZOSTER-049. Secondary objectives included VE against HZ from 1 month post-dose 2 in the ZOE-50/-70 studies until the end of Y4 of ZOSTER-049 (Y10 post-vacci- nation), persistence of vaccine-induced humoral immunogenicity in terms of anti-glycoprotein E (gE) antibody and cell-mediated immune response in terms of frequency of gE-specific CD4[2+] T-cells and safety. VE analysis for ZOSTER-049 used historical control estimates from the ZOE-50/-70 placebo groups. 결과: ZOSTER-049 enrolled 7,413 participants and 7,277 were included in VE analyses (Fig. 2). During 4 years of follow-up in ZOSTER-049, overall VE against HZ was 81.6% (95% confidence interval [CI]: 75.2-86.6). From 1 month post-dose 2 in ZOE-50/-70 until Y4 of ZOSTER-049, overall VE was 89.0% (95% CI: 85.6-91.3). In ZOSTER-049, anti-gE antibody concentrations persisted >5 times above pre-vaccination up to Y10 post-vaccination (Fig. 3A). Frequency of gE-specific CD4[2+] T-cells remained above pre-vaccination from Y6 to Y10 post-vaccination (Fig. 3B). No safety signals were identified until the end of ZOSTER-049 Y4. 결론: VE against HZ and immune responses to RZV remained high until the end of the observation period for this Y4 interim analysis, suggesting sustained clinical benefit of RZV in adults ≥50 YOA for at least 10 years after vaccination. RZV safety profile remained clinically acceptable. [ABSTRACT FROM AUTHOR]

Aim To genotype cytokine polymorphisms in the Macedonian population as a part of the international project Cytokine Polymorphism Component (CPC). Methods The sample consisted of 125 healthy unrelated individuals, 46 men and 79 women, aged 20-35 years. All individuals were of Macedonian origin and nationality, Christian Orthodox religion, and residents of different regions of the Republic of Macedonia. Blood samples were collected after written consent was obtained, DNA was isolated from peripheral blood leukocytes by the phenolchloroform extraction method, and the samples were stored in the Anthropology section of the Macedonian Human DNA Bank (hDNAMKD). Fourteen cytokine genes were identified as candidates: gamma-interferon (IFNγ); interleukin (IL)1 alpha (IL-1α); IL-1 beta (IL-1β); IL-1 receptor (IL-1R); IL-1R antagonist (IL-1RA); IL-2; IL-4; IL-4 receptor alpha (IL-4Rα); IL-6; IL-10; IL-12B; TGF beta 1 (TGF-1β); and TNF alpha (TNF-α). Cytokine genotyping for the anthropology samples was performed by polymerase chain reaction with sequence-specific priming (PCR-SSP) (Heidelberg kit). The population genetics analysis package, PyPop, was used for the analysis of the cytokine data for this report. Results The frequency of alleles for some single nucleotide polymorphisms (SNP) varied from 0.967 for TGF-β1 cdn25/G and 0.920 for TNF-α-238/G, to 0.914 for IL-1α-889/C, indicating common "wild type" allele in those cytokines. For the most SNPs, the test of neutrality showed negative value for Fnd statistic, which indicated balancing selection operating on the alleles at that locus. Fnd was negative and significantly different from 0 for IFNγ UTR5644 and TGF-β1 cdn10 (P=0.006 and P= 0.007, respectively). Most of SNPs showed a good fit with HWP expectations. A few SNPs (IL-1α-889, IL-1β-511, IL-1β+3962, and IFNγ UTR5644) were not in HWP (P≤0.005), and Guo and Thompson Hardy Weinberg Output (GTHWO) was significant (P≤0.005). The most frequent haplotypes for TGF-β1 wereTG (0.491) and CG (0.476), with the absence of TGF-β1/TC haplotype in the sample from the Macedonian population. Test of neutrality showed negative value for F nd statistic (Ewens-Watterson test of neutrality) which indicated balancing selection operating on the haplotypes at that locus, except for the IL-4 haplotypes, where it showed a positive value for Fnd statistic,but without significance. Fnd was negative and significantly different from 0 for IL-10 haplotypes (P=0.002). In the sample from the Macedonian population, D' was equal to 1 in all haplotypes with P values < 0.0001, except for TNF-α (P≤0.012), which indicated that one or more haplotypes were missing. Conclusion The analysis of cytokine alleles, genotypes, and haplotypes in the sample from the Macedonian population showed a good fit with Hardy Weinberg equilibrium for most of SNPs and can be used for anthropological comparisons, as well as for association studies with different diseases. [ABSTRACT FROM AUTHOR]

The aim of our research was to examine changes in the immune system of the rats influenced by the elevated ambient temperature. Male Wistar rats were divided, into 2 groups and housed at 20 ± 2° C (n=64, control group) and 35 ± 1° C (n=74, experimental group), during precise timing of 1, 4, 7, 14, 21, and 30 days. All the animals were given food and water ad libitum, and were lighted during 12 hours per day. We have measured IgG, IgG1, IG2a, IgG2b and IgG2c. The obtained results showed significant elevation in the level of IgG after 4 and 7 days (+32%), IgG2a after 7th (+88%), 14th and 21nd day (+110%). IgG2b after 14 days (+60%) at 35 ± 1° C compared with the control group at 20 ± 2° C. IgG1 level was not affected and IgG2c showed significant decrease after 21st day at 35 ± 1° C. In conclusion, during the elevated ambient temperature the immune system is activated as one of the regulation mechanisms in homeostasis and survival of the population. [ABSTRACT FROM AUTHOR]

Objective: To examine the possible role of 22 cytokine gene polymorphisms in host susceptibility to or protection against tuberculosis (TB) in Macedonians., Method: 301 healthy unrelated individuals and 75 patients with pulmonary TB were studied. Cytokine genotyping was performed by PCR with sequence-specific priming (PCR-SSP) (Heidelberg kit)., Results: TNF-alpha-238/G, IL-1R psti1970/C, IL-1beta + 3962/T:T, IL-4-1098/T:T, IFNgamma utr5644/A:A, IL-10-1082/G:G, IL-4-590/C:C, IL-10/ATC, IL-4/TCT, IL-4/TCC, IL-10/ATC:GCC, IL-4/TCT:TTT, IL-4/TCC:TTC, IL-10/GCC:GCC and IL-4/TCC:TCC were positively associated with TB, while protective association was identified for IL-4-098/G, IL-1beta + 3962/C, IFNgamma utr5644/T, IL-1beta + 3962/C:T, IL-4-1098/G:T, IL-4-590/C:T, IFNgamma utr5644/A:T, IL-4/GCC, IL-4/TTC and IL-4/GCC:TTC., Conclusion: These results suggest that some cytokine polymorphisms are significantly associated and affect host susceptibility/resistance to TB in Macedonians.

The aim of this study was to investigate the occurrence of ambiguous allele combinations at the allele group level of HLA-A, -C and -B loci in the Macedonian population. The DNA samples of 214 healthy unrelated Macedonian volunteers were obtained from our DNA Bank. HLA typing was performed using the IHWG-RLS method (Reverse Line Strip, Roche Molecular Systems, USA) consisting of PCR amplification of exon 2 and 3 of HLA-A, -B and -C genes, followed by hybridization. The statistical analysis of the observed ambiguity frequency was performed by using the Arleqin Software. At the HLA-A locus only one ambiguous allele combination at the allele group level in 214 samples was observed with a frequency of 0.467% (1/214 = 0.467%). A total of 6 different HLA-C ambiguous allele combinations at the allele group level in twelve samples with a frequency of 5.607% (12/214 = 5.607%) and 11 different for HLA-B locus in nineteen samples with a frequency of 8.879% (19/214 = 8.879%) were observed in 214 samples. In conclusion we can say that analysis of the frequency of allele ambiguities revealed that the ambiguities involved some of the most common alleles in our population, obviating the need to introduce ambiguity resolution technique(s)/strategies in the HLA laboratory.