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Between Microbial Genomes With The Human Genome And The Distribution Of Igg Subclasses In Myasthenia Gravis And Primary Sjogren's Syndrome, The Potential Pathological Significance

Posted on:2011-11-25Degree:MasterType:Thesis
Country:ChinaCandidate:Y D LiuFull Text:PDF
GTID:2204360305967695Subject:Clinical Laboratory Science
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Comparison between human genome and bacterial genomesBackground The interaction between bacteria and human is still incomplete. With the recent availability of many microbial genomes and human genomes, as well as the series of basic local alignment search tool (BLAST) programs, a new perspective to gain insight into the interaction of bacteria with human is possible. This study is to determine the possibility of existence of sequences identity between the genomes of bacteria and human, and try to explain this phenomenon in term of bacteriophages and other genetic mobile elements.Methods BLAST searches of the genomes of bacteria against human genome were performed using the resources of the National Center for Biotechnology Information (NCBI). In order to investigate a possible explanation for the identical sequence between bacterial genomes and human genome, BLAST was run to search of various genomes of bacteriophages and plasmids against the genome of human and bacteria. The GeneBank accession numbers of these genomes are accessible on the web (http://www.ncbi.nlm.nih.gov/sites/entrez?db=Genome). Criteria for significance of sequence identity were that the sequence had 100% identity with at least 17 nucleotides.Results All studied bacteria contain variable numbers of short regions of sequence identity to the genome of human, which ranged from 27nt to 84nt. They were found at multiple sites within the human genome. According to the BLAST results, we found that bacteria with larger genome often have more identical regions than their smaller genome counterpart. For a specific organism, most of the identical sequences were found in noncoding regions of human genome, but some identical sequences were located within a host gene-coding sequence. For example, in the case of Staphylococcus epidermidis,12 out of 45 identical sequences found within gene-coding regions. Most functions of the identical sequences found in the human genome were related to the many physiological functions of human cells. They involved in the cell signal transduction, cell metabolism and DNA replication by encoding the enzymes, receptors, gene regulator and other proteins. For bacteriophages, these sequences ranged from 24 to 33nt, while for the plasmids, they ranged from 22 to 34 nt. These short sequence identities found in these mobile genetic elements could also be found in the genomes of bacteria, but the sequences identity found between the genomes of bacteria and human were not identified in the genome of bacteriophages or plasmids.Conclusion The short regions of sequence identity existed between the genomes of bacteria and human, and a hypothesis that viruses, especially bacteriophages, might play a significant role in shaping the genomes of bacterial and human, and contribute to the short the regions sequence identity is developed. The distribution of IgG subclasses in myasthenia gravis patients suggests all the four subclasses might involve in the pathogenesisBackground Myasthenia gravis (MG) is an autoimmune disease characterized by preferential production of a variety of autoantibodies. We aimed to investigate serum IgG (Immunoglobulin G) subclass levels in MG patients.Methods IgG subclass levels of sera from 85 patients with MG were determined by immunonephelometric assay. To elucidate the possible pathogenic role of IgG subclass in MG, we sought for statistical relationships between IgG subclasses concentrations and other related factors, including sex, age at onset, disease duration and disease severity. Fifty normal controls were also measured.Results Overall, the median levels of IgG1, IgG2, IgG3 and IgG4 in MG patients were 7360 mg/L,5750 mg/L,860 mg/L and 340 mg/L, respectively. The serum levels of all the four IgG subclasses in MG patients were significantly higher than those in normal controls (p=0.000, p=0.000, p=0.000, p=0.029, respectively). The level of IgG1 subclass were statistically higher in female group than that in male group (median value 9140 mg/L vs.7294 mg/L, p=0.039), but the serum IgG2, IgG3, and IgG4 concentrations were similar between the two groups. The concentration of IgG4 subclass in late-onset group was significantly higher than that in early-onset group (median value 473.4 mg/L vs.343.5 mg/L, p=0.023). There was a significant inverse correlation between the concentrations of IgG2 and IgG4 and disease duration according to Spearman's Nonparametric Correlation (r=0.265, p=0.014; r=0.316, p=0.003, respectively), but there was no correlation or dependence between the levels of IgGl and IgG3,and disease duration. No statistically difference in the levels of all the four IgG subclasses were found among the different MG subgroups or-among the normal thymus group (Table 3), thymus hyperplasia group, and thymoma group (p>0.05). Similarly, no difference in the levels of all the four IgG subclasses was found between thymectomy group and non-thymectomy group.Conclusion This study shows that all the four IgG subclasses increased in MG patients, which might provide a useful insight into the pathological process operating in the disease. In addition, the pathological function of IgG4 in MG needs to be investigated. Preferentially IgG subclasses production may contribute to the inflammatory process of primary Sjogren's syndromeBackground The pathogenic mechanisms of primary Sjogren's syndrome (pSS) remain largely unknown, in part a consequence of the heterogeneity of the disease. Antibody subclasses can reflect specific immunological processes because different subclasses have different Fc effector functions, such as complement activation, antibody-dependent cell cytotoxicity and phagocytosis of immune complexes. Hence, one approach to the antoantibody pathogenicity is to determine their IgG subclass distribution. We aimed to investigate serum IgG subclass levels in pSS patients, which may be indicative of the underlying pathological patterns involved in pSS.Methods IgG subclass concentrations of the sera from 155 patients with pSS were analyzed by immunonephelometric assay. Fifty patients with SLE and fifty normal controls were also measured.Results Overall, the median levels of IgGl, IgG2, IgG3 and IgG4 in pSS patients were 11300 mg/L,6130 mg/L,961 mg/L and 142 mg/L, respectively. The serum levels of IgG1, IgG2 and IgG3 subclasses in pSS patients were significantly higher than those in normal controls (p=0.000,p=0.000,p=0.000, respectively), but the IgG4 value was significantly lower than that in normal controls (p=0.002). Between pSS group and SLE group, the IgG4 value in pSS were significantly lower than that in SLE (p=0.040), while no significant difference in the serum levels of IgGl, IgG2 and IgG3 were observed (p>0.05). The level of IgG1 subclass was statistically higher in anti-Ro or La positive group than that in negative group (median value 6930 mg/L vs. 12750 mg/L, p=0.000), but the serum IgG4 concentration was lower than that in negative group (median value 236.5 mg/L vs.139 mg/L, p=0.046) (Table 3). However, among the group without systemic disorders and the groups with one or multi-extraglandular disorders, the IgG subclass distributions were similar, no significant difference was found (data not shown). There was a significant positive correlation between the concentration of IgG3 and the disease duration according to Spearman's Nonparametric Correlation (r=0.359, p=0.000), but no correlation between the levels of other IgG subclasses and disease duration was observed.Conclusion This study showed that IgG subclasses were preferentially produced during the process of pSS, which may indicate a pathogenic potential of these subclasses in the process of pSS. Further studies on the investigation of the machnisms for the elevation of IgG2 should be strengthened.
Keywords/Search Tags:Human genome sequence, short sequence identity, bacterial genome sequence, basic local alignment search tool, Autoimmune myasthenia gravis, Autoantibodies, IgG subclass concentrations, Immunonephelometric assay, Primary Sj(o|¨)gren's syndrome
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