Autoantibodies in children with chronic inflammatory lung diseases

124 sera of children with chronic bronchitis, chronic pneumonia, bronchial asthma, exogenic allergic alveolitis, congenital developmental defects of the lungs and the syndrome of the situs inversus of organs were examined with a view to study the state of humoral immunity to tissues. The study was carried out by means of the enzyme-linked immunosorbent assay with the use of collagen, elastin, DNA (native and denaturated), membrane antigens of the lung, the liver, the small intestine and the large intestine. Among all groups of patients autoimmune disturbances, manifested by a rise in the level of autoantibodies of different specificity, were registered. The degree of manifestation of autoimmune disturbances depended on the kind of pathology. After treatment a decrease in the level of autoantibodies was registered in the examinees.     

Lymphoid neogenesis in chronic inflammatory diseases

The frequent observation of organized lymphoid structures that resemble secondary lymphoid organs in tissues that are targeted by chronic inflammatory processes, such as autoimmunity and infection, has indicated that lymphoid neogenesis might have a role in maintaining immune responses against persistent antigens. In this Review, we discuss recent progress in several aspects of lymphoid neogenesis, focusing on the similarities with lymphoid tissue development, the mechanisms of induction, functional competence and pathophysiological significance. As more information on these issues becomes available, a better understanding of the role of lymphoid neogenesis in promoting chronic inflammation might eventually lead to new strategies to target immunopathological processes.     

Meta-analysis of TYK2 gene polymorphisms association with susceptibility to autoimmune and inflammatory diseases

The aim of our meta-analysis was to quantitatively summarize the association of TYK2 gene polymorphisms with autoimmune and inflammatory diseases. 11 studies that included data from 21497 cases and 22647 controls were identified. OR was used as a measure of the effect of the association in a fixed/random effect model. Meta-analysis was performed for six TYK2 gene polymorphisms (rs34536443, rs2304256, rs280523, rs280519, rs12720270 and rs12720356). Significant association was found in rs34536443 (C versus G: OR = 0.76, 95% CI = 0.69–0.84, P < 0.00001; GC + CC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0005; CC versus GG + GC: OR = 0.76, 95% CI = 0.28–2.05, P = 0.58; CC versus GG: OR = 0.74, 95% CI = 0.27–2.02, P = 0.56; GC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0006) and rs2304256 (A versus C: OR = 0.78, 95% CI = 0.70–0.87, P < 0.0001; CA + AA versus CC: OR = 0.69, 95% CI = 0.59–0.81, P < 0.0001; AA versus CC + CA: OR = 0.75, 95% CI = 0.66–1.00, P = 0.05; AA versus CC: OR = 0.64, 95% CI = 0.47–0.86, P = 0.003; CA versus CC: OR = 0.70, 95% CI = 0.60–0.83, P < 0.0001) in TYK2 gene, but not for the other polymorphisms (rs280523, rs280519, rs12720270, and rs12720356). This meta-analysis demonstrates that autoimmune and inflammatory diseases is associated with TYK2 gene rs34536443 and rs2304256 polymorphisms, but not rs280523, rs280519, rs12720270 and rs12720356.     

Manipulation of TGF-beta to control autoimmune and chronic inflammatory diseases

Defining the mechanisms whereby transforming growth factor-beta (TGF-beta) controls physiologic inflammation and the immune response and how it contributes to pathology when it is dysregulated is critical to our ability to manipulate the levels and activity of this potent cytokine for therapeutic benefit. In keeping with its dichotomous nature, recent evidence suggests that overproduction and/or activation contribute to persistent inflammation and that antagonists of TGF-beta delivered locally can break the cycle of leukocyte recruitment and fibrotic sequelae. On the other hand, systemic routing of TGF-beta can also inhibit inflammatory pathogenesis by multiple mechanisms as exemplified by systemic injections of the protein and by recent gene transfer studies. In addition, enhanced levels of circulating endogenous TGF-beta appear to be an instrument of suppression during the development of oral tolerance, cyclosporin treatment, and following administration of retinoic acid. Although treatment of autoimmune and chronic inflammatory diseases is an important goal, the multiplicity of actions of TGF-beta and the nearly ubiquitous expression of TGF-beta and its receptors dictate a cautious approach to the use of this powerful cytokine as a therapeutic agent.     

Haemophilus influenzae biovars in patients with acute and chronic inflammatory lung diseases

In the study of the biological properties of 175 H. influenzae strains isolated from patients with acute and chronic inflammatory lung diseases (ILD) and from donors, a wide spread of biovars I, II and III (according to Kilian) was revealed; these biovars constituted 80% of the cultures under study. In donors, H. influenzae strains were characterized by a wide spectrum of biovars, but biovars I, II and VI constituted more than a half (64.2%) of the strains obtained in the course of these investigations. In acute ILD, only H. influenzae biovars I, II and III were isolated with the prevalence of biovar II (56.4%). In chronic ILD, all H. influenzae biovars were represented, but biovars II and III prevailed (58.7%). The four-fold difference in the occurrence of H. influenzae strains belonging to undetermined biovars was established in donors in comparison with ILD patients (46.7 +/- 9.8% and 12.0 +/- 2.5%; p less than 0.001).     

Cytokine single nucleotide polymorphisms in Iranian patients with pulmonary tuberculosis

BACKGROUND: Several genes coding for different cytokines may affect host susceptibility to tuberculosis. METHODS: In the present study, the allele and genotype frequencies of a number polymorphic genes coding for cytokines or cytokine receptors were investigated in Iranian patients with pulmonary tuberculosis (PTB). RESULTS: From the IL-1 cluster, a positive, significant difference was found at position -889, where the T/T genotype was over represented in PTB patients (p = 0.01); a positive, significant increase was found in the IL1R PstI 1970 C/C genotype, where the C allele was over represented in the PTB patients (p = 0.01). A significant negative association at codon 10 TGF-beta, T allele, was shown in our patients and the C allele and C/C genotype were over represented in the PTB patients (P<0.005). For TNF-alpha at position -238, we found a negative association for the G/A genotype and a positive association for the G/G genotype (p = 0.0009). Significant negative associations at position -590 IL-4, T allele and the T/T genotype were shown in our patients (p = 0.0007); also, the C allele and T/C genotype were significantly increased in our patients (P<0.05). With IL-6 at -174, G/G increased and G/C decreased significantly in the patients (P<0.005). CONCLUSION: Pro-inflammatory cytokines such as TNF-alpha and TGF-beta seem to be decreased, and IL-6 increased in PTB patients.     

Analysis of polymorphisms of genes associated with immune response and tissue remodeling in occupational chronic bronchitis

The involvement of polymorphisms of genes encoding immune response-associated molecules (LTA, TNFA, IL1B, ILRN, IL8, IL10, VDBP), matrix metalloproteinases (MMP1, MMP2, MMP3, MMP9, MMP12, ADAM33), and tissue and serum inhibitors of metalloproteinases (TIMP2, TIMP3, SERPINA1, SERPINA3) in the predisposition to occupational chronic bronchitis was assessed by PCR-RFLP analysis in groups of patients (n = 122) and healthy workers (n = 166). It was found that occupational chronic bronchitis was associated with polymorphisms of VDBP (P_adj = 0.00005, OR_adj = 2.06), MMP1 (P_adj = 0.00002, OR_adj = 2.57), ADAM33 (P_adj = 0.0004, OR_adj = 2.52), and IL8 (P_adj = 0.0058, OR_adj = 2.87). The most significant association was observed for the VDBP polymorphism 1296T>G. The VDBP haplotype GC*1S by the loci 1296T>G and 1307C>A was an informative susceptibility marker (P_adj = 0.0001, OR_adj = 2.60, 95%CI (1.62–4.19)). There was also a significant interaction between the VDBP polymorphism 1307C>A and the duration of occupational exposure to hazardous factors (Pinteraction = 0.02). Apparently, the investigated polymorphisms of VDBP, MMP1, ADAM33, and IL8 contribute to the genetic susceptibility to chronic bronchitis induced by dust and toxic agents.     

Cytokine polymorphisms in silicosis and other pneumoconioses

Silicosis and coal workers' pneumoconiosis are complex multifactorial lung diseases whose etiopathogenesis are not well defined. It is generally accepted that fibrotic lung disorders are mediated by macrophage-derived cytokines and growth factors. There is evidence showing a crucial role for tumor necrosis factor-a (TNF-alpha) and interleukin-1 (IL-1) in inflammation caused by silica dust and in the transition from simple to progressive massive fibrosis. In this review we discuss genetic polymorphisms responsible for regulating the production of these proinflammatory cytokines and their role in modifying silicosis severity.     

Cytokine single nucleotide polymorphisms in Iranian populations

Cytokines are important immunomodulatory molecules involved in immune responses against microorganisms; they also have an important role in the setting of immune system disorders. Cytokine single nucleotide polymorphisms have been extensively studied in different, normal populations as well as in association with disease. Cytokine gene polymorphisms are potentially important as genetic predictors of disease susceptibility, clinical outcome, and as a tool for anthropological studies. In this study, samples have been collected from 455 healthy individuals located in different regions of Iran (Tehran, Yazd, Sistan and Balochistan). Allele and genotype frequencies of cytokine SNP, including: IL-1alpha, IL-1beta, IL-1R, IL-1RA, IL-2, IL-4, IL-4RA, IL-6, IL-10, IL-12, TNF-alpha, TGF-beta and IFN-gamma were investigated, using the PCR-SSP method. Allele frequencies in Tehran and Yazd populations were similar, except for TGF-beta. Allele frequencies in Sistani & Baloch populations were similar at all positions, except for IL-1beta at position of -511 and IFN-gamma genes at position UTR5644; there were some differences in allele frequencies comparing these populations with the Yazd population, including: IL-4, IL-6, IL-10, TGF-beta and TNF-alpha. Although some significant differences were observed for some cytokines, it seems that the cytokine gene polymorphism profile of the Iranian population is similar to that of Caucasians, particularly the Italian population.     

Streptococcus pneumoniae serotypes in children with chronic inflammatory diseases of the respiratory organs

During the 7-year period of observation (1982-1988) the serotypes of 276 pneumococcal strains isolated from children with chronic bronchopulmonary diseases were studied. Among the serotypes of pneumococci under study, serotypes 6, 19 and 15 held the leading place and included a half of all typed pneumococci. Dynamic observation on the serotype composition of pneumococci revealed periodic fluctuations in the occurrence of some types/groups. The regional analysis of different serotypes of pneumococci showed the common occurrence of serogroups 6 and 19, as well as some regional features in the circulation of serotypes 6, 10, 3 and rarely occurring serotypes. The study revealed that any new exacerbation of the chronic bronchopulmonary process is caused by pneumococci of some other serotype. Pneumococcal strains, resistant (3.4%) and sensitive (1.8%) to penicillin, were detected; most of them belonged to serogroup 19.     

Cytokine polymorphisms in silicosis and other pneumoconioses

Silicosis and coal workers' pneumoconiosis are complex multifactorial lung diseases whose etiopathogenesis are not well defined. It is generally accepted that fibrotic lung disorders are mediated by macrophage-derived cytokines and growth factors. There is evidence showing a crucial role for tumor necrosis factor- (TNF-) and interleukin-1 (IL-1) in inflammation caused by silica dust and in the transition from simple to progressive massive fibrosis. In this review we discuss genetic polymorphisms responsible for regulating the production of these proinflammatory cytokines and their role in modifying silicosis severity.     

Cytokine gene polymorphisms and susceptibility to cutaneous leishmaniasis in Iranian patients

Cutaneous Leishmaniasis (CL) is one of the most prevalent clinical forms of leishmaniasis. Preliminary data suggest that cytokine gene polymorphisms can contribute to resistance or susceptibility to CL. Therefore, we investigated the association of functional polymorphisms in four cytokine genes with susceptibility to, and clinical outcome of CL. A total of 201 patients with self-healing cutaneous leishmaniasis (SCL) and 92 asymptomatic infected controls (AIC) from Fars province as well as 58 patients with chronic cutaneous leishmaniasis (CCL) and their 688 normal controls (normal Iranian population or NIP) who were collected from the different areas of Iran were included in the study. The allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) or PCR-RFLP (restriction fragment length polymorphism) methods were used for genotyping. The frequency of TNF-alpha -308 G-->A and TNF-beta +252 G-->A gene polymorphisms were not different between studied groups. Distribution of IFN-gamma +874 A-->T and IL-4 -590 C-->T polymorphism were also compared between SCl or CCL patients and their controls. IFN-gamma +874 A-->T polymorphism was less common in CCL patients compared to the NIP (chi(2)=12.53, p=0.0019). Significant differences in frequency of IL-4 -590 C -->T polymorphism were also found between the SCL and AIC (chi(2)=8.64, p=0.003). In conclusion, our results suggest that functional genetic variants in the IL-4 promoter could influence the risk of developing CL while the polymorphism in the first intron of the IFN-gamma gene might influence the progression of disease towards CCL.     

Complex search for antiprotease-protease enzyme gene polymorphisms in patients with chronic obstructive pulmonary diseases

Based on the protease-antiprotease hypothesis in the pathogenesis of chronic lung diseases, we investigated the influence of Z and S mutations and TaqI-polymorphism of alpha1-antitrypsin gene (PI) and Ala - 15Thr polymorphism in signal peptide of alpha1-antichymotrypsin gene (AACT) in patients with COPD (n = 239), nonobstructive chronic bronchitis (n = 34), brochiectases (n = 33), chronic infant lung disease (n = 151) and cystic fibrosis (n = 57). The allele and genotype frequency of any genetic polymorphism was not statistically different between the groups and control subjects (n = 225). Furthermore, promoter polymorphism G - 1607GG in interstitial collagenase gene (MMP1) was determined in patients with COPD, chronic nonobstructive bronchitis and bronchiectases. In patients with COPD it was marked prevalence of mutant homozygous genotype GG/GG compared to controls (30.6 % and 18.0%, respectively, OR = 1.99; 95% CI 1.11-3.59). These findings suggest that genetic polymorphism in the promoter of MMPI gene may be associated with individual susceptibility to the development of COPD.     

Changes in vaginal microbiocenosis in patients with chronic pelvic inflammatory diseases following antibiotic therapy

The species composition of the vaginal microorganisms in healthy women and in patients with chronic pelvic inflammatory diseases before and after treatment in a gynecological hospital was studied. The study revealed that antibiotic therapy did not lead to complete clinical convalescence. During bacteriological investigation of patients changes in vaginal microbiocenosis, manifested by a decreased number of microbial species, an increased proportion of Escherichia coli, the occurrence of Staphylococcus aureus, a decreased number of Lactobacillus ssp., were observed. Antibiotic therapy aggravated the dysbiotic microbial picture of the vagina.     

Biochemical polymorphisms in goats with special reference to the Hungarian Native breed

Biochemical polymorphisms (haemoglobin, serum transferrin, serum albumin, serum amylase, red cell phosphohexose isomerase, red cell carbonic anhydrase, ceruloplasmin and aryl esterase) of 224 Hungarian Native female goats and 21 imported male goats (German Improved, Saanen, Nubian, Slovakian White) have been studied.
On the basis of the observed gene frequency values these polymorphic traits cannot be used efficiently in parentage control work or in correlation studies. There was no apparent association between the haemoglobin and transferrin type of the females and their reproductive performance.