Pub Date : 2017-12-15DOI: 10.4172/1745-7580.1000142
Dandan Li, W. Ren, Zhilong Jiang, Lei Zhu
Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is characterized by the uncontrolled progressive lung inflammation. Macrophage plays a key role in the pathogenesis of ALI/ARDS. Macrophage pyroptosis is a process of cell death with release of pro-inflammatory cytokines IL-1beta and IL-18. We hypothesize that macrophage pyroptosis may partially account for the uncontrolled lung inflammation of ALI/ARDS. In this study, we observed greater macrophage pyroptosis in the LPS-treated macrophages and ALI/ARDS mouse model. The expression of NLRP3, IL-1beta and cleavage of Caspase-1 were significantly elevated after LPS treatment, accompanied with more activation of p38 MAPK signaling in vitro and in vivo. However, blocking p38 MAPK signaling through inhibitor SB203580 significantly suppressed the acute lung injury and excessive lung inflammation in vivo, consistent with the reduced expression of NLRP3 inflammasome, IL-1beta and cleavage of Caspaase-1. SB203580 significant decreased the population of Caspase-1+propidium iodide (PI)+ pyroptotic cells and expression of NLRP3/ IL-1beta in the treated rat NR8383 macrophage cell lines. However, we observed more population of Annexin V+PIapoptotic cells after blocking p38 MAPK signaling. The results indicated that blockade of p38 MAPK signaling skewed macrophage cell death from pro-inflammatory pyroptosis towards non-inflammatory apoptosis. The effects may contribute to the attenuated acute lung injury and excessive inflammation in the SB203580-treated mice. The results provide a novel therapeutic strategy for the treatment of the uncontrolled lung inflammation among patients with ALI/ARDS
{"title":"The Role of p38 MAPK Signaling Pathway in Macrophage Pyroptosis and Murine Acute Lung Injury","authors":"Dandan Li, W. Ren, Zhilong Jiang, Lei Zhu","doi":"10.4172/1745-7580.1000142","DOIUrl":"https://doi.org/10.4172/1745-7580.1000142","url":null,"abstract":"Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is characterized by the uncontrolled progressive lung inflammation. Macrophage plays a key role in the pathogenesis of ALI/ARDS. Macrophage pyroptosis is a process of cell death with release of pro-inflammatory cytokines IL-1beta and IL-18. We hypothesize that macrophage pyroptosis may partially account for the uncontrolled lung inflammation of ALI/ARDS. In this study, we observed greater macrophage pyroptosis in the LPS-treated macrophages and ALI/ARDS mouse model. The expression of NLRP3, IL-1beta and cleavage of Caspase-1 were significantly elevated after LPS treatment, accompanied with more activation of p38 MAPK signaling in vitro and in vivo. However, blocking p38 MAPK signaling through inhibitor SB203580 significantly suppressed the acute lung injury and excessive lung inflammation in vivo, consistent with the reduced expression of NLRP3 inflammasome, IL-1beta and cleavage of Caspaase-1. SB203580 significant decreased the population of Caspase-1+propidium iodide (PI)+ pyroptotic cells and expression of NLRP3/ IL-1beta in the treated rat NR8383 macrophage cell lines. However, we observed more population of Annexin V+PIapoptotic cells after blocking p38 MAPK signaling. The results indicated that blockade of p38 MAPK signaling skewed macrophage cell death from pro-inflammatory pyroptosis towards non-inflammatory apoptosis. The effects may contribute to the attenuated acute lung injury and excessive inflammation in the SB203580-treated mice. The results provide a novel therapeutic strategy for the treatment of the uncontrolled lung inflammation among patients with ALI/ARDS","PeriodicalId":73347,"journal":{"name":"Immunome research","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2017-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49031143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-12-15DOI: 10.4172/1745-7580.1000145
T. Nagai, T. Okamura, Y. Tanaka, D. Kobayashi, Takahiro Kobayashi, H. Akita, T. Yasui
The neutrophil-to-lymphocyte ratio (NLR), a measure of systemic inflammation, has been reported to be a predictive parameter of patient prognosis. We speculated that the NLR is decreased in renal cell carcinoma (RCC) patients in whom interleukin (IL)-2 is effective. In this study, we retrospectively examined the usefulness of the NLR as a prognostic factor using three cases of RCC treated with long-term IL-2. In all three cases, the NLR remained less than 2.7 during IL-2 treatment, suggesting its effectiveness as a marker. During interferon-α or molecular targeted drug therapy, the NLR was unstable, regardless of treatment effectiveness, but a sudden rise in the NLR tended to suggest massive radiographic progression and worse prognosis. The results suggested that the NLR might serve as a useful marker for therapies when determining prognosis.
{"title":"The Neutrophil-to-Lymphocyte Ratio as A Prognostic Factor For Long-Term Interleukin-2 Use in Renal Cell Carcinoma","authors":"T. Nagai, T. Okamura, Y. Tanaka, D. Kobayashi, Takahiro Kobayashi, H. Akita, T. Yasui","doi":"10.4172/1745-7580.1000145","DOIUrl":"https://doi.org/10.4172/1745-7580.1000145","url":null,"abstract":"The neutrophil-to-lymphocyte ratio (NLR), a measure of systemic inflammation, has been reported to be a predictive parameter of patient prognosis. We speculated that the NLR is decreased in renal cell carcinoma (RCC) patients in whom interleukin (IL)-2 is effective. In this study, we retrospectively examined the usefulness of the NLR as a prognostic factor using three cases of RCC treated with long-term IL-2. In all three cases, the NLR remained less than 2.7 during IL-2 treatment, suggesting its effectiveness as a marker. During interferon-α or molecular targeted drug therapy, the NLR was unstable, regardless of treatment effectiveness, but a sudden rise in the NLR tended to suggest massive radiographic progression and worse prognosis. The results suggested that the NLR might serve as a useful marker for therapies when determining prognosis.","PeriodicalId":73347,"journal":{"name":"Immunome research","volume":" ","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48925927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-10-25DOI: 10.4172/1745-7580.1000143
A. Bansal, A. Upadhyay
Enhancers are DNA sequences containing multiple transcription factor binding sites, could be present upstream, downstream or within the gene. They are meant to enhance the expression of their target genes. Major features of enhancers are: clusters of transcription factor binding sites, evolutionary conserved non-coding DNA sequence and biochemical marks such as histone modification and chromatin structure. We have used genome-wide approach to identify sequence of the putative enhancer of rhomboid gene in eleven different species of Drosophila viz. melanoagaster, yakuba, ananassae, erecta, grimshawi, mojavensis, persimilis, pseudoobscura, sechellia, virilise and willistoni using genome browser ClusterDraw. Analyses of the cluster formation of dorsal, twist and snail motifs of the rhomboid gene suggested a range of 1 to 15 binding sites among the species. Among the eleven species used in this study for prediction of enhancer element, four have enhancer element at upstream and five have downstream whereas two species have on both side of the rhomboid gene.
{"title":"Genome-Wide Identification and Analysis of Putative Rhomboid Gene Enhancers in Multiple Drosophila Species","authors":"A. Bansal, A. Upadhyay","doi":"10.4172/1745-7580.1000143","DOIUrl":"https://doi.org/10.4172/1745-7580.1000143","url":null,"abstract":"Enhancers are DNA sequences containing multiple transcription factor binding sites, could be present upstream, downstream or within the gene. They are meant to enhance the expression of their target genes. Major features of enhancers are: clusters of transcription factor binding sites, evolutionary conserved non-coding DNA sequence and biochemical marks such as histone modification and chromatin structure. We have used genome-wide approach to identify sequence of the putative enhancer of rhomboid gene in eleven different species of Drosophila viz. melanoagaster, yakuba, ananassae, erecta, grimshawi, mojavensis, persimilis, pseudoobscura, sechellia, virilise and willistoni using genome browser ClusterDraw. Analyses of the cluster formation of dorsal, twist and snail motifs of the rhomboid gene suggested a range of 1 to 15 binding sites among the species. Among the eleven species used in this study for prediction of enhancer element, four have enhancer element at upstream and five have downstream whereas two species have on both side of the rhomboid gene.","PeriodicalId":73347,"journal":{"name":"Immunome research","volume":"13 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2017-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46685424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-06-05DOI: 10.4172/1745-7580.1000135
Malaz Abdelbagi, Tarteel Hassan, Mohammed Shihabeldin, S. Bashir, Elkhaleel Ahmed, E. Mohamed, S. Hafiz, Abdah Abdelmonim, T. Hamid, S. Awad, A. Hamdi, Khoubieb Ali, Mohammed A Hassan
Background: African horse sickness (AHS) is a viral disease of equidae. It is transmitted by hematophagous Culicoides midges (Diptera, Ceratopogonidae) and causes severe disease in horse that can lead to death. African Horse Sickness Virus (AHSV) is a double-stranded RNA (dsRNA) virus with ten genome segments encoding seven structural proteins (VP1-VP7) and four non-structural proteins (NS1, NS2, NS3, NS3A). The aim of this study is to analyze (VP2) protein of the African Horse Sickness Virus (AHSV) strains reported in the National Center for Biotechnology Information database (NCBI) database to select all possible epitopes that can be used to design a peptide vaccine. Materials and methods: A total of 27 outer capsid protein (VP2) sequences of African Horse Sickness Virus (AHSV) were retrieved from the National Center for Biotechnology Information database (NCBI) (https://www.ncbi.nlm. nih.gov/protein/?term=VP2+African+horse+sickness+virus) in the 7th of September 2016. On them, several tests were conducted using Immune Epitope Analysis Database (IEDB) to detect the highly conserved immunogenic epitopes of B and T cells from which all possible epitopes that can be used as a therapeutic peptide vaccine to be selected. Results and Discussion: Regarding epitopes that would elicit an antibody immune response, “FSPEYY, DKVVEDPESY and YDTDQNVV “were proposed to stimulate B cell. While 5 epitopes for each MHC I and II were addressed as potentially promising epitopes as they bound the highest number of alleles, all these epitopes were found to have a high binding affinity and the lowest binding energy to equine MHC class I molecule (ELA-A3) haplotype in the structural level. The epitopes “YAYCLILAL and YTFGNKFLL” were represented because they were bound to the largest number of alleles. In spite of binding to 4 alleles the epitope WFFDYYATL was represented because it has the lowest global energy. To our knowledge there is no epitope based vaccine for the African Horse Sickness Virus (AHSV) using in silico approaches.
{"title":"Immunoinformatics Prediction of Peptide-Based Vaccine Against AfricanHorse Sickness Virus","authors":"Malaz Abdelbagi, Tarteel Hassan, Mohammed Shihabeldin, S. Bashir, Elkhaleel Ahmed, E. Mohamed, S. Hafiz, Abdah Abdelmonim, T. Hamid, S. Awad, A. Hamdi, Khoubieb Ali, Mohammed A Hassan","doi":"10.4172/1745-7580.1000135","DOIUrl":"https://doi.org/10.4172/1745-7580.1000135","url":null,"abstract":"Background: African horse sickness (AHS) is a viral disease of equidae. It is transmitted by hematophagous \u0000 Culicoides midges (Diptera, Ceratopogonidae) and causes severe disease in horse that can lead to death. African Horse Sickness Virus (AHSV) is a double-stranded RNA (dsRNA) virus with ten genome segments encoding seven \u0000 structural proteins (VP1-VP7) and four non-structural proteins (NS1, NS2, NS3, NS3A). The aim of this study is \u0000 to analyze (VP2) protein of the African Horse Sickness Virus (AHSV) strains reported in the National Center for \u0000 Biotechnology Information database (NCBI) database to select all possible epitopes that can be used to design a \u0000 peptide vaccine. \u0000Materials and methods: A total of 27 outer capsid protein (VP2) sequences of African Horse Sickness Virus \u0000 (AHSV) were retrieved from the National Center for Biotechnology Information database (NCBI) (https://www.ncbi.nlm. \u0000 nih.gov/protein/?term=VP2+African+horse+sickness+virus) in the 7th of September 2016. On them, several tests were \u0000 conducted using Immune Epitope Analysis Database (IEDB) to detect the highly conserved immunogenic epitopes of B \u0000 and T cells from which all possible epitopes that can be used as a therapeutic peptide vaccine to be selected. \u0000Results and Discussion: Regarding epitopes that would elicit an antibody immune response, “FSPEYY, \u0000 DKVVEDPESY and YDTDQNVV “were proposed to stimulate B cell. While 5 epitopes for each MHC I and II were \u0000 addressed as potentially promising epitopes as they bound the highest number of alleles, all these epitopes were \u0000 found to have a high binding affinity and the lowest binding energy to equine MHC class I molecule (ELA-A3) \u0000 haplotype in the structural level. The epitopes “YAYCLILAL and YTFGNKFLL” were represented because they \u0000 were bound to the largest number of alleles. In spite of binding to 4 alleles the epitope WFFDYYATL was represented \u0000 because it has the lowest global energy. To our knowledge there is no epitope based vaccine for the African Horse \u0000 Sickness Virus (AHSV) using in silico approaches.","PeriodicalId":73347,"journal":{"name":"Immunome research","volume":"13 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2017-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46127084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-05-23DOI: 10.4172/1745-7580.1000134
Mawadda Abd-Elraheem Awad-Elkareem, Soada A. Osman, H. Mohamed, H. Hassan, Ahmed Hamdi Abu-haraz, K. A. Abd-elrahman, M. Salih
Merkel cell Polyomavirus is non-enveloped, dsDNA virus belonging to Polyomaviridae family linked to an uncommon aggressive skin malignancy. The poor prognosis and limited understanding of disease pathogenesis warrants innovative treatment. In this current study we aim to predict TB cell immunogenic epitopes from the VP1 protein of all merkel cell polyomavirus strain which will aid in effective epitope based vaccine design using immuoinformatics approaches. We retrieved 423 full-length VP1 protein sequences of merkel cell polyomaviruse virus species from the NCBI database. These sequences were analyzed to determine the conserved region and were used to predict the epitopes using the IEDB immunoinformatics algorithms. For B cell three epitope were predicted as peptide vaccine (QEKTVY, KTVYPK, and QEKTVYP). For T cell the predicted Class-I peptides (SLFSNLMPK, LQMWEAISV and LLVKGGVEV) were found to cover the maximum number of MHC I alleles. The highest scoring Class II MHC binding peptides were (IELYLNPRM, ISSLINVHY and INSLFSNLM). Further experiments will need to be undertaken to confirm the potential of these predicted epitopes in a future efficacious vaccine development.
{"title":"Prediction and Conservancy Analysis of Multiepitope Based PeptideVaccine Against Merkel Cell Polyomavirus: An ImmunoinformaticsApproach","authors":"Mawadda Abd-Elraheem Awad-Elkareem, Soada A. Osman, H. Mohamed, H. Hassan, Ahmed Hamdi Abu-haraz, K. A. Abd-elrahman, M. Salih","doi":"10.4172/1745-7580.1000134","DOIUrl":"https://doi.org/10.4172/1745-7580.1000134","url":null,"abstract":"Merkel cell Polyomavirus is non-enveloped, dsDNA virus belonging to Polyomaviridae family linked to an \u0000 uncommon aggressive skin malignancy. The poor prognosis and limited understanding of disease pathogenesis \u0000 warrants innovative treatment. In this current study we aim to predict TB cell immunogenic epitopes from the \u0000 VP1 protein of all merkel cell polyomavirus strain which will aid in effective epitope based vaccine design using \u0000 immuoinformatics approaches. We retrieved 423 full-length VP1 protein sequences of merkel cell polyomaviruse \u0000 virus species from the NCBI database. These sequences were analyzed to determine the conserved region and were \u0000 used to predict the epitopes using the IEDB immunoinformatics algorithms. For B cell three epitope were predicted \u0000 as peptide vaccine (QEKTVY, KTVYPK, and QEKTVYP). For T cell the predicted Class-I peptides (SLFSNLMPK, \u0000 LQMWEAISV and LLVKGGVEV) were found to cover the maximum number of MHC I alleles. The highest scoring \u0000 Class II MHC binding peptides were (IELYLNPRM, ISSLINVHY and INSLFSNLM). Further experiments will need \u0000 to be undertaken to confirm the potential of these predicted epitopes in a future efficacious vaccine development.","PeriodicalId":73347,"journal":{"name":"Immunome research","volume":"13 1","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2017-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41586949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-05-22DOI: 10.4172/1745-7580.1000133
S. Sedda, E. Troncone, M. Imeneo, G. Monteleone
Inflammatory bowel diseases (IBD) are chronic inflammatory pathologies of the gut, characterized by a relapsing-remitting course. Although IBD pathogenesis is not fully understood, epidemiological and experimental data suggest that multiple environmental factors can, in genetically predisposed individuals, trigger an excessive immune response directed against the antigens of the normal intestinal microflora, which eventually leads to the tissue damage. Defects in the physiological mechanisms/factors of counter-regulation contribute to amplify and sustain such a detrimental response. For instance, in inflamed tissue of IBD patients there is diminished activity of the immunesuppressive cytokine transforming growth factor (TGF)-β1, due to elevated levels of Smad7, an intracellular inhibitor of TGF-β1 signaling. Consistently, knockdown of Smad7 with a specific antisense oligonucleotide suppresses inflammatory signals in cultured intestinal cells of IBD patients and in the gut of mice with IBD-like experimental colitis. Moreover, treatment of patients with active Crohn’s disease, one of the two major IBD in human beings, with Mongersen, an oral compound containing Smad7 antisense oligonucleotide, is accompanied by induction of clinical remission. Altogether these data indicate that targeting Smad7 represents a promising approach to modulate the ongoing mucosal inflammation in IBD.
{"title":"Smad7 as a Target for Immunomodulation Strategy in Inflammatory BowelDiseases","authors":"S. Sedda, E. Troncone, M. Imeneo, G. Monteleone","doi":"10.4172/1745-7580.1000133","DOIUrl":"https://doi.org/10.4172/1745-7580.1000133","url":null,"abstract":"Inflammatory bowel diseases (IBD) are chronic inflammatory pathologies of the gut, characterized by a relapsing-remitting course. Although IBD pathogenesis is not fully understood, epidemiological and experimental data suggest that multiple environmental factors can, in genetically predisposed individuals, trigger an excessive immune response directed against the antigens of the normal intestinal microflora, which eventually leads to the tissue damage. Defects in the physiological mechanisms/factors of counter-regulation contribute to amplify and sustain such a detrimental response. For instance, in inflamed tissue of IBD patients there is diminished activity of the immunesuppressive cytokine transforming growth factor (TGF)-β1, due to elevated levels of Smad7, an intracellular inhibitor of TGF-β1 signaling. Consistently, knockdown of Smad7 with a specific antisense oligonucleotide suppresses inflammatory signals in cultured intestinal cells of IBD patients and in the gut of mice with IBD-like experimental colitis. Moreover, treatment of patients with active Crohn’s disease, one of the two major IBD in human beings, with Mongersen, an oral compound containing Smad7 antisense oligonucleotide, is accompanied by induction of clinical remission. Altogether these data indicate that targeting Smad7 represents a promising approach to modulate the ongoing mucosal inflammation in IBD.","PeriodicalId":73347,"journal":{"name":"Immunome research","volume":"13 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/1745-7580.1000133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43099814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-05-01DOI: 10.4172/1745-7580.10000132
T. Hiwasa, Go Tomiyoshi, Rika Nakamura, Natsuko Shinmen, Hideyuki Kuroda, M. Kunimatsu, S. Mine, T. Machida, E. Sato, M. Takemoto, A. Hattori, Kazuki Kobayashi, H. Kawamura, Ryoichi Ishibashi, K. Yokote, K. Kitamura, Mikiko Ohno, Po-min Chen, E. Nishi, K. Ono, T. Kimura, H. Takizawa, K. Kashiwado, Kamitsukasa, T. Wada, A. Aotsuka, K. Sunami, E. Kobayashi, Y. Yoshida, T. Matsutani, Y. Iwadate, M. Mori, A. Uzawa, M. Muto, K. Sugimoto, S. Kuwabara, Y. Iwata, Y. Kobayashi, J. Terada, T. Matsumura, S. Sakao, K. Tatsumi, Masaaki Ito, H. Shimada, Xiao-meng Zhang, R. Kimura, Hao Wang, K. Iwase, H. Ashino, Akiko Taira, E. Arita, K. Goto, T. Kudo, H. Doi
Abstract Background: The discovery and development of novel biomarkers that could facilitate early diagnosis and thus prevent the progression of atherosclerosis-related diabetes mellitus (DM), cerebral infarction (CI), and cardiovascular disease (CVD) has garnered much research interest. Notably, recent reports have described a number of highly sensitive antibody markers. In this study, we aimed to identify additional antibody markers that would facilitate screening. Methods: The amplified luminescent proximity homogeneous assay (AlphaLISA) method, which incorporates glutathione- or streptavidin-donor beads and anti-human-IgG-acceptor beads, was used to evaluate serum antibody levels in serum samples. The protein array method was used for the initial screening, and peptide arrays were used to identify epitope sites. Results: The protein array identified SH3 domain-binding protein 5 (SH3BP5) as a target antigen of serum IgG antibodies in the sera of patients with atherosclerosis. We prepared recombinant glutathione S-transferase (GST)- fused SH3BP5 protein. Peptide arrays revealed that the epitope site recognized by serum antibodies is located within amino acids 161–174 of SH3BP5. AlphaLISA revealed significantly higher serum antibody levels against both the SH3BP5 protein and peptide in patients with DM, acute-phase CI, transient ischemic attack, CVD or chronic kidney disease (CKD), than in healthy donors. Furthermore, areas under the receiver operating characteristic curves of these antibodies were higher in patients with CKD and DM than in other patients. Spearman correlation analysis revealed associations between the serum antibody levels against SH3BP5 peptide and artery stenosis, hypertension, and smoking. Conclusions: The serum anti-SH3BP5 antibody marker appears to be useful for estimating the progress of atherosclerosis and may discriminate atherosclerosis associated with hypertension and/or habitual smoking.
{"title":"Serum SH3BP5-specific Antibody Level is a Biomarker of Atherosclerosis","authors":"T. Hiwasa, Go Tomiyoshi, Rika Nakamura, Natsuko Shinmen, Hideyuki Kuroda, M. Kunimatsu, S. Mine, T. Machida, E. Sato, M. Takemoto, A. Hattori, Kazuki Kobayashi, H. Kawamura, Ryoichi Ishibashi, K. Yokote, K. Kitamura, Mikiko Ohno, Po-min Chen, E. Nishi, K. Ono, T. Kimura, H. Takizawa, K. Kashiwado, Kamitsukasa, T. Wada, A. Aotsuka, K. Sunami, E. Kobayashi, Y. Yoshida, T. Matsutani, Y. Iwadate, M. Mori, A. Uzawa, M. Muto, K. Sugimoto, S. Kuwabara, Y. Iwata, Y. Kobayashi, J. Terada, T. Matsumura, S. Sakao, K. Tatsumi, Masaaki Ito, H. Shimada, Xiao-meng Zhang, R. Kimura, Hao Wang, K. Iwase, H. Ashino, Akiko Taira, E. Arita, K. Goto, T. Kudo, H. Doi","doi":"10.4172/1745-7580.10000132","DOIUrl":"https://doi.org/10.4172/1745-7580.10000132","url":null,"abstract":"Abstract Background: The discovery and development of novel biomarkers that could facilitate early diagnosis and thus prevent the progression of atherosclerosis-related diabetes mellitus (DM), cerebral infarction (CI), and cardiovascular disease (CVD) has garnered much research interest. Notably, recent reports have described a number of highly sensitive antibody markers. In this study, we aimed to identify additional antibody markers that would facilitate screening. Methods: The amplified luminescent proximity homogeneous assay (AlphaLISA) method, which incorporates glutathione- or streptavidin-donor beads and anti-human-IgG-acceptor beads, was used to evaluate serum antibody levels in serum samples. The protein array method was used for the initial screening, and peptide arrays were used to identify epitope sites. Results: The protein array identified SH3 domain-binding protein 5 (SH3BP5) as a target antigen of serum IgG antibodies in the sera of patients with atherosclerosis. We prepared recombinant glutathione S-transferase (GST)- fused SH3BP5 protein. Peptide arrays revealed that the epitope site recognized by serum antibodies is located within amino acids 161–174 of SH3BP5. AlphaLISA revealed significantly higher serum antibody levels against both the SH3BP5 protein and peptide in patients with DM, acute-phase CI, transient ischemic attack, CVD or chronic kidney disease (CKD), than in healthy donors. Furthermore, areas under the receiver operating characteristic curves of these antibodies were higher in patients with CKD and DM than in other patients. Spearman correlation analysis revealed associations between the serum antibody levels against SH3BP5 peptide and artery stenosis, hypertension, and smoking. Conclusions: The serum anti-SH3BP5 antibody marker appears to be useful for estimating the progress of atherosclerosis and may discriminate atherosclerosis associated with hypertension and/or habitual smoking.","PeriodicalId":73347,"journal":{"name":"Immunome research","volume":"13 1","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/1745-7580.10000132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46147977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-03-28DOI: 10.4172/1745-7580.C1.011
Ebtekar Masoumeh Amir Kalvanagh Parisa Soleimanjahi Hoorie Zahra, Kokaei Parviz
{"title":"Preparation and characterization of PLGA nanoparticles containing plasmid DNA encoding human IFNlambda- 1: Beginning for promising researches","authors":"Ebtekar Masoumeh Amir Kalvanagh Parisa Soleimanjahi Hoorie Zahra, Kokaei Parviz","doi":"10.4172/1745-7580.C1.011","DOIUrl":"https://doi.org/10.4172/1745-7580.C1.011","url":null,"abstract":"","PeriodicalId":73347,"journal":{"name":"Immunome research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70942125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-03-24DOI: 10.4172/1745-7580.10000131
Zheng Jz, R. Wang, Liu Rr, Chen Jj, Q. Wei, Wu Xy, Pang Xw, J. Ek, Liu Xy
Abstract Nitrogen-fixing Rhizobia were discovered more than 100 years ago. They are classified into two clades, Alphaand Beta-rhizobia. Their symbiotic function is remarkable, but its origin and evolution has been confusing from a phylogenetic perspective. In this study, we make use of 33 publicly available complete genome sequences downloaded from NCBI, which consist of bacteria and archaea, and focus on 10 strains, constructing symbiotic structural maps for them based on their genomes and previous gene annotations. Phylogenies of the symbiosisessential genes nodA and nifH were examined. Although large incongruities with some hypotheses from previous studies were detected by the present study, we support the general concept that Beta-rhizobia were the original symbionts of legumes, but that their symbotic genes originated from a common ancestor to the Alpha-rhizobia. We also confirm that the spread and maintenance of symbiotic genes occurred mainly through vertical transmission, with lateral transfer playing a significant, albeit supporting, role.
{"title":"The Structure and Evolution of Beta-Rhizobial Symbiotic Genes Deducedfrom Their Complete Genomes","authors":"Zheng Jz, R. Wang, Liu Rr, Chen Jj, Q. Wei, Wu Xy, Pang Xw, J. Ek, Liu Xy","doi":"10.4172/1745-7580.10000131","DOIUrl":"https://doi.org/10.4172/1745-7580.10000131","url":null,"abstract":"Abstract Nitrogen-fixing Rhizobia were discovered more than 100 years ago. They are classified into two clades, Alphaand Beta-rhizobia. Their symbiotic function is remarkable, but its origin and evolution has been confusing from a phylogenetic perspective. In this study, we make use of 33 publicly available complete genome sequences downloaded from NCBI, which consist of bacteria and archaea, and focus on 10 strains, constructing symbiotic structural maps for them based on their genomes and previous gene annotations. Phylogenies of the symbiosisessential genes nodA and nifH were examined. Although large incongruities with some hypotheses from previous studies were detected by the present study, we support the general concept that Beta-rhizobia were the original symbionts of legumes, but that their symbotic genes originated from a common ancestor to the Alpha-rhizobia. We also confirm that the spread and maintenance of symbiotic genes occurred mainly through vertical transmission, with lateral transfer playing a significant, albeit supporting, role.","PeriodicalId":73347,"journal":{"name":"Immunome research","volume":"13 1","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2017-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/1745-7580.10000131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48824684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-02-17DOI: 10.4172/1745-7580.10000130
Polona Žigon, Aleš AmbrožiÄ, Polonca Mali, Matija TomšiÄ, S. S. Šemrl, Saša ÄuÄnik
Objective: Studies on antiphospholipid antibodies have mainly focused on the IgG and IgM isotypes, with only a few investigating the pathogenic significance of IgA antiphospholipid antibodies. Positive IgA anticardiolipin (aCL) and IgA anti-β2 glycoprotein I (anti-β2GPI) were reported to be predominantly associated with other antiphospholipid antibodies, making it difficult to understand the role of IgA alone. Recently, antibodies against phosphatidylserine/ prothrombin (aPS/PT) IgG and IgM have been indicated as a potential marker for antiphospholipid syndrome (APS). Our previous study reported that IgG and IgM aPS/PT showed highest association with lupus anticoagulant (LA) activity of all tested antiphospholipid antibodies, while no studies to date have investigated possible clinical benefits of IgA aPS/PT. In this study, we determined the prevalence of IgA aPS/PT in patients with systemic autoimmune diseases and evaluated their clinical association to thrombosis and obstetric complications. Methods: 254 patients with systemic autoimmune diseases were screened for LA, aCL, anti-β2GPI and aPS/PT (for IgG, IgM, IgA isotypes). Results: An overall prevalence of 63/254 (25%) was found for IgA aPS/PT in our cohort of patients. IgA aPS/PT were statistically significantly associated to LA activity and to both arterial and venous thrombosis, however no association was found to obstetric complications. Median levels of IgA aPS/PT were significantly higher in APS patients than in the non-APS patient control group comprising systemic lupus erythematosus, rheumatoid arthritis and Sjogren’s syndrome patients. Conclusion: Although IgA aPS/PT were predominantly associated with other antiphospholipid antibodies this study first confirmed their presence in APS patient samples and also showed a clear association of IgA aPS/PT to thrombosis and LA activity.
{"title":"The Prevalence and Clinical Significance of Iga Anti-Phosphatidylserine/Prothrombin Antibodies in Systemic Autoimmune Diseases","authors":"Polona Žigon, Aleš AmbrožiÄ, Polonca Mali, Matija TomšiÄ, S. S. Šemrl, Saša ÄuÄnik","doi":"10.4172/1745-7580.10000130","DOIUrl":"https://doi.org/10.4172/1745-7580.10000130","url":null,"abstract":"Objective: Studies on antiphospholipid antibodies have mainly focused on the IgG and IgM isotypes, with only a few investigating the pathogenic significance of IgA antiphospholipid antibodies. Positive IgA anticardiolipin (aCL) and IgA anti-β2 glycoprotein I (anti-β2GPI) were reported to be predominantly associated with other antiphospholipid antibodies, making it difficult to understand the role of IgA alone. Recently, antibodies against phosphatidylserine/ prothrombin (aPS/PT) IgG and IgM have been indicated as a potential marker for antiphospholipid syndrome (APS). Our previous study reported that IgG and IgM aPS/PT showed highest association with lupus anticoagulant (LA) activity of all tested antiphospholipid antibodies, while no studies to date have investigated possible clinical benefits of IgA aPS/PT. In this study, we determined the prevalence of IgA aPS/PT in patients with systemic autoimmune diseases and evaluated their clinical association to thrombosis and obstetric complications. Methods: 254 patients with systemic autoimmune diseases were screened for LA, aCL, anti-β2GPI and aPS/PT (for IgG, IgM, IgA isotypes). Results: An overall prevalence of 63/254 (25%) was found for IgA aPS/PT in our cohort of patients. IgA aPS/PT were statistically significantly associated to LA activity and to both arterial and venous thrombosis, however no association was found to obstetric complications. Median levels of IgA aPS/PT were significantly higher in APS patients than in the non-APS patient control group comprising systemic lupus erythematosus, rheumatoid arthritis and Sjogren’s syndrome patients. Conclusion: Although IgA aPS/PT were predominantly associated with other antiphospholipid antibodies this study first confirmed their presence in APS patient samples and also showed a clear association of IgA aPS/PT to thrombosis and LA activity.","PeriodicalId":73347,"journal":{"name":"Immunome research","volume":"13 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2017-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/1745-7580.10000130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45412408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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