ImmunogeneticsPub Date : 2023-08-01DOI: 10.1007/s00251-023-01304-w
Michael Levinson, Mohamed Khass, Peter D Burrows, Harry W Schroeder
{"title":"Germline-enforced enrichment for charged amino acids in TCR beta chain (TCRβ) complementarity determining region 3 (CDR-B3) alters T cell development, repertoire content, and antigen recognition.","authors":"Michael Levinson, Mohamed Khass, Peter D Burrows, Harry W Schroeder","doi":"10.1007/s00251-023-01304-w","DOIUrl":"https://doi.org/10.1007/s00251-023-01304-w","url":null,"abstract":"<p><p>T cell receptor beta chain (TCRβ) diversity (Dβ) gene segments are highly conserved across evolution, with trout Dβ1 sequence identical to human and mouse Dβ1. A key conserved feature is enrichment for glycine in all three Dβ reading frames (RFs). Previously, we found that replacement of mouse Dβ1 with a typical immunoglobulin D<sub>H</sub> sequence, which unlike Dβ is enriched for tyrosine, leads to an increase in the use of tyrosine in TCRβ complementarity determining region 3 (CDR-B3) after thymic selection, altering T cell numbers, CDR-B3 diversity, and T cell function. To test whether the incorporation of charged amino acids into the Dβ sequence in place of glycine would also influence T cell biology, we targeted the TCRβ locus with a novel glycine-deficient DβDKRQ allele that replaces Dβ1 coding sequence with charged amino acids in all three reading frames. Developing T cells using DβDKRQ expressed TCR CDR-B3s depleted of tyrosine and glycine and enriched for germline-encoded lysine, arginine, and glutamine. Total thymocytes declined in number during the process of β selection that occurs during the transition from the DN3bc to DN4 stage. Conventional thymocyte and T cell numbers remained reduced at all subsequent thymic stages and in the spleen. By contrast, regulatory T cell numbers were increased in Peyer's patches and the large intestine. In terms of functional consequences, T cell reactivity to an ovalbumin immunodominant epitope was reduced. These findings buttress the view that natural selection of Dβ sequence is used to shape the pre-immune TCRβ repertoire, affecting both conventional and regulatory T cell development and influencing epitope recognition.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 4","pages":"341-353"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10209946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-08-01DOI: 10.1007/s00251-023-01308-6
Nourelhoda E Hassan, Walaa A Moselhy, Ehab B Eldomany, Emad Farah Mohamad Kholef
{"title":"Evaluation of miRNA-16-2-3P, miRNA-618 levels and their diagnostic and prognostic value in the regulation of immune response during SARS Cov-2 infection.","authors":"Nourelhoda E Hassan, Walaa A Moselhy, Ehab B Eldomany, Emad Farah Mohamad Kholef","doi":"10.1007/s00251-023-01308-6","DOIUrl":"https://doi.org/10.1007/s00251-023-01308-6","url":null,"abstract":"<p><p>Following the announcement of the pandemic of COVID-19 in December 2019, several studies focused on how to early predict the severity of the disease in symptomatic and asymptomatic patients. Many cytokines including interleukin-6, interleukin-8, and tumor necrotic factors have been concluded as strong indicators for COVID-19 infection. Additionally, miRNAs have been associated with dysregulation in the immune system. The aim of this study are the following: (1) to estimate the level of miRNA-16-2-3P, miRNA-618, IL-8, IL-1β as predictors for SARS-CoV-2 complications in PCR negative and positive patients; (2) to assess the biological role and effect of these miRNAs on SARS-CoV-2 pathogenicity. Our study showed that the level of IL-1β had been significantly associated with patient who need hospitalization, also the alteration of the level of miRNA-16-2-3P, miRNA-618 is positively correlated with the admission of these patients and influence the outcomes of SARS-cov-2 infection. Measurement of miRNA-16-2-3P, miRNA-618, IL-1β could be a good predictor of COVID-19 patient outcome. However the measurement of IL-8 levels during immune responses in the admitted and in ICU patients could have a prognostic value.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 4","pages":"403-410"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9852707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prognostic value of the WT-1 gene combined with recurrent cytogenetic genes in acute myeloid leukemia.","authors":"Qing Zhang, Linlin Liu, Haotian Yan, Xiyang Ren, Mei Zhou, Shudao Xiong, Huiping Wang, Qianshan Tao, Zhimin Zhai","doi":"10.1007/s00251-023-01314-8","DOIUrl":"https://doi.org/10.1007/s00251-023-01314-8","url":null,"abstract":"<p><p>Wilms tumor gene 1 (WT-1 gene) is overexpressed in most patients with acute myeloid leukemia (AML) and is an indicator for minimal residual disease (MRD) monitoring, but because the WT-1 gene has relatively low specificity, further studies of the prognostic value of a combination of the WT-1 and other genes are needed. The aim of this study was to explore the prognostic value of the WT-1 gene combined with recurrent cytogenetic genes in AML. In AML, the transcript expression of the WT-1 gene was closely related to leukemic tumor burden and acted as an accurate molecular indicator for MRD detection. Most patients with low expression levels of the WT-1 gene after induction and consolidation therapy were significantly associated with favorable relapse-free survival (RFS) and overall survival (OS), but 17.6% of patients relapsed and died of primary disease. However, when analyzing the WT-1 gene combined with recurrent cytogenetic genes, none of the patients with low expression levels of the WT-1 gene and recurrent cytogenetic genes negative relapsed and died in the median follow-up time of 19 months (range: 3-94 months). Thus, the combination of the WT-1 gene and recurrent cytogenetic genes is a more accurate indicator for MRD monitoring and prognosis evaluation in AML patients.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 4","pages":"395-401"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunological assessment of a patient with Omenn syndrome resulting from compound heterozygous mutations in the RAG1 gene.","authors":"Wenjun Mou, Zixin Yang, Xiaojiao Wang, Mingyan Hei, Yajuan Wang, Jingang Gui","doi":"10.1007/s00251-023-01309-5","DOIUrl":"https://doi.org/10.1007/s00251-023-01309-5","url":null,"abstract":"<p><p>The recombination activating gene 1 (RAG1) is essential for V(D)J recombination during T- and B-cell development. In this study, we presented a case study of a 41-day-old female infant who exhibited symptoms of generalized erythroderma, lymphadenopathy, hepatosplenomegaly, and recurrent infections including suppurative meningitis and septicemia. The patient showed a T<sup>+</sup>B<sup>-</sup>NK<sup>+</sup> immunophenotype. We observed an impaired thymic output, as indicated by reduced levels of naive T cells and sjTRECs, coupled with a restricted TCR repertoire. Additionally, T-cell CFSE proliferation was impaired, indicating a suboptimal T-cell response. Notably, our data further revealed that T cells were in an activated state. Genetic analysis revealed a previously reported compound heterozygous mutation (c. 1186C > T, p. R396C; c. 1210C > T, p. R404W) in the RAG1 gene. Structural analysis of RAG1 suggested that the R396C mutation might lead to the loss of hydrogen bonds with neighboring amino acids. These findings contribute to our understanding of RAG1 deficiency and may have implications for the development of novel therapies for patients with this condition.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 4","pages":"385-393"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10209961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-08-01DOI: 10.1007/s00251-023-01311-x
Edward C So, Hua Zhou, Ariana Greenwell, Erin E Burch, Yaping Ji, Emmanuel Y Mérigeon, Henrik S Olsen, Søren M Bentzen, David S Block, Xiaoyu Zhang, Scott E Strome
{"title":"Complement component C1q is an immunological rheostat that regulates Fc:Fc[Formula: see text]R interactions.","authors":"Edward C So, Hua Zhou, Ariana Greenwell, Erin E Burch, Yaping Ji, Emmanuel Y Mérigeon, Henrik S Olsen, Søren M Bentzen, David S Block, Xiaoyu Zhang, Scott E Strome","doi":"10.1007/s00251-023-01311-x","DOIUrl":"https://doi.org/10.1007/s00251-023-01311-x","url":null,"abstract":"<p><p>Though binding sites for the complement factor C1q and the canonical fragment crystallizable (Fc) gamma receptors (Fc[Formula: see text]Rs) on immunoglobulin G (IgG) molecules overlap, how C1q decoration of immune complexes (ICs) influences their ability to engage Fc[Formula: see text]Rs remains unknown. In this report, we use recombinant human Fc multimers as stable IC mimics to show that C1q engagement of ICs directly and transiently inhibits their interactions with Fc[Formula: see text]RIII (CD16) on human natural killer (NK) cells. This inhibition occurs by C1q engagement alone as well as in concert with other serum factors. Furthermore, the inhibition of Fc[Formula: see text]RIII engagement mediated by avid binding of C1q to ICs is directly associated with IC size and dependent on the concentrations of both C1q and Fc multimers present. Functionally, C1q-mediated Fc blockade limits the ability of NK cells to induce the upregulation of the cosignaling molecule, 4-1BB (CD137), and to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). Although C1q is traditionally viewed as a soluble effector molecule, we demonstrate that C1q may also take on the role of an \"immunologic rheostat,\" buffering Fc[Formula: see text]R-mediated activation of immune cells by circulating ICs. These data define a novel role for C1q as a regulator of immune homeostasis and add to our growing understanding that complement factors mediate pleiotropic effects.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 4","pages":"369-383"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9842395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-06-01DOI: 10.1007/s00251-022-01290-5
Carene Anne Alene Ndong Sima, Dayna Smith, Desiree C Petersen, Haiko Schurz, Caitlin Uren, Marlo Möller
{"title":"The immunogenetics of tuberculosis (TB) susceptibility.","authors":"Carene Anne Alene Ndong Sima, Dayna Smith, Desiree C Petersen, Haiko Schurz, Caitlin Uren, Marlo Möller","doi":"10.1007/s00251-022-01290-5","DOIUrl":"https://doi.org/10.1007/s00251-022-01290-5","url":null,"abstract":"<p><p>Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death due to a single bacterial agent, with approximately 10.6 million people developing active disease and 1.6 million deaths reported globally in 2021. After exposure, some, but not all individuals, will become infected with the bacillus. However, only a small fraction (approximately 5 to 15%) of these individuals will progress to clinical disease, while in the remainder, infection is seemingly contained, and no signs of clinical disease are shown. Numerous observations have advocated for the role of host genetics in the display of these inter-individual variabilities in infection and disease phenotypes. In this review, we will provide an overview of the approaches, findings and limitations of the very first studies investigating TB genetic susceptibility to more recent studies. Lastly, we highlight several approaches, namely, linkage analyses and association studies, proposed to discover genetic markers associated with TB susceptibility. This review also explored the concept of polygenic risk scores (PRS) for prediction of tuberculosis susceptibility. The identification of host genetic factors influencing TB susceptibility/resistance is paramount to not only better understand the physiopathology of the disease but also explore more effective approaches for the development of both optimal preventive measures (i.e. better vaccines) and treatments of TB disease.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 3","pages":"215-230"},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9572021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-06-01DOI: 10.1007/s00251-022-01288-z
William H Palmer, Paul J Norman
{"title":"The impact of HLA polymorphism on herpesvirus infection and disease.","authors":"William H Palmer, Paul J Norman","doi":"10.1007/s00251-022-01288-z","DOIUrl":"https://doi.org/10.1007/s00251-022-01288-z","url":null,"abstract":"<p><p>Human Leukocyte Antigens (HLA) are cell surface molecules, central in coordinating innate and adaptive immune responses, that are targets of strong diversifying natural selection by pathogens. Of these pathogens, human herpesviruses have a uniquely ancient relationship with our species, where coevolution likely has reciprocating impact on HLA and viral genomic diversity. Consistent with this notion, genetic variation at multiple HLA loci is strongly associated with modulating immunity to herpesvirus infection. Here, we synthesize published genetic associations of HLA with herpesvirus infection and disease, both from case/control and genome-wide association studies. We analyze genetic associations across the eight human herpesviruses and identify HLA alleles that are associated with diverse herpesvirus-related phenotypes. We find that whereas most HLA genetic associations are virus- or disease-specific, HLA-A*01 and HLA-A*02 allotypes may be more generally associated with immune susceptibility and control, respectively, across multiple herpesviruses. Connecting genetic association data with functional corroboration, we discuss mechanisms by which diverse HLA and cognate receptor allotypes direct variable immune responses during herpesvirus infection and pathogenesis. Together, this review examines the complexity of HLA-herpesvirus interactions driven by differential T cell and Natural Killer cell immune responses.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 3","pages":"231-247"},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10069628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-06-01DOI: 10.1007/s00251-023-01296-7
Vitor R C Aguiar, Erick C Castelli, Richard M Single, Arman Bashirova, Veron Ramsuran, Smita Kulkarni, Danillo G Augusto, Maureen P Martin, Maria Gutierrez-Arcelus, Mary Carrington, Diogo Meyer
{"title":"Comparison between qPCR and RNA-seq reveals challenges of quantifying HLA expression.","authors":"Vitor R C Aguiar, Erick C Castelli, Richard M Single, Arman Bashirova, Veron Ramsuran, Smita Kulkarni, Danillo G Augusto, Maureen P Martin, Maria Gutierrez-Arcelus, Mary Carrington, Diogo Meyer","doi":"10.1007/s00251-023-01296-7","DOIUrl":"https://doi.org/10.1007/s00251-023-01296-7","url":null,"abstract":"<p><p>Human leukocyte antigen (HLA) class I and II loci are essential elements of innate and acquired immunity. Their functions include antigen presentation to T cells leading to cellular and humoral immune responses, and modulation of NK cells. Their exceptional influence on disease outcome has now been made clear by genome-wide association studies. The exons encoding the peptide-binding groove have been the main focus for determining HLA effects on disease susceptibility/pathogenesis. However, HLA expression levels have also been implicated in disease outcome, adding another dimension to the extreme diversity of HLA that impacts variability in immune responses across individuals. To estimate HLA expression, immunogenetic studies traditionally rely on quantitative PCR (qPCR). Adoption of alternative high-throughput technologies such as RNA-seq has been hampered by technical issues due to the extreme polymorphism at HLA genes. Recently, however, multiple bioinformatic methods have been developed to accurately estimate HLA expression from RNA-seq data. This opens an exciting opportunity to quantify HLA expression in large datasets but also brings questions on whether RNA-seq results are comparable to those by qPCR. In this study, we analyze three classes of expression data for HLA class I genes for a matched set of individuals: (a) RNA-seq, (b) qPCR, and (c) cell surface HLA-C expression. We observed a moderate correlation between expression estimates from qPCR and RNA-seq for HLA-A, -B, and -C (0.2 ≤ rho ≤ 0.53). We discuss technical and biological factors which need to be accounted for when comparing quantifications for different molecular phenotypes or using different techniques.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 3","pages":"249-262"},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9595180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-06-01Epub Date: 2023-01-31DOI: 10.1007/s00251-023-01293-w
Laura Mora-Bitria, Becca Asquith
{"title":"Innate receptors modulating adaptive T cell responses: KIR-HLA interactions and T cell-mediated control of chronic viral infections.","authors":"Laura Mora-Bitria, Becca Asquith","doi":"10.1007/s00251-023-01293-w","DOIUrl":"10.1007/s00251-023-01293-w","url":null,"abstract":"<p><p>Killer-cell immunoglobulin-like receptors (KIRs) are mainly expressed on natural killer (NK) cells and are key regulators of innate immune responses. NK cells are the first responders in the face of infection and help promote placentation during pregnancy; the importance of KIRs in these NK-mediated processes is well-established. However, mounting evidence suggests that KIRs also have a prominent and long-lasting effect on the adaptive immune system. Here, we review the evidence for the impact of KIRs on T cell responses with a focus on the clinical significance of this interaction.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 3","pages":"269-282"},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9887252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10322369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunogeneticsPub Date : 2023-06-01DOI: 10.1007/s00251-022-01280-7
Edward J Hollox, Sandra Louzada
{"title":"Genetic variation of glycophorins and infectious disease.","authors":"Edward J Hollox, Sandra Louzada","doi":"10.1007/s00251-022-01280-7","DOIUrl":"https://doi.org/10.1007/s00251-022-01280-7","url":null,"abstract":"<p><p>Glycophorins are transmembrane proteins of red blood cells (RBCs), heavily glycosylated on their external-facing surface. In humans, there are four glycophorin proteins, glycophorins A, B, C and D. Glycophorins A and B are encoded by two similar genes GYPA and GYPB, and glycophorin C and glycophorin D are encoded by a single gene, GYPC. The exact function of glycophorins remains unclear. However, given their abundance on the surface of RBCs, it is likely that they serve as a substrate for glycosylation, giving the RBC a negatively charged, complex glycan \"coat\". GYPB and GYPE (a closely related pseudogene) were generated from GYPA by two duplication events involving a 120-kb genomic segment between 10 and 15 million years ago. Non-allelic homologous recombination between these 120-kb repeats generates a variety of duplication alleles and deletion alleles, which have been systematically catalogued from genomic sequence data. One allele, called DUP4, encodes the Dantu NE blood type and is strongly protective against malaria as it alters the surface tension of the RBC membrane. Glycophorins interact with other infectious pathogens, including viruses, as well as the malarial parasite Plasmodium falciparum, but the role of glycophorin variation in mediating the effects of these pathogens remains underexplored.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 3","pages":"201-206"},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9511628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}