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Human Immunology

Sâmila Natiane Ferreira, Mauro de Meira Leite, Monique Suellen Lima da Silveira, Erika Ferreira Dos Santos, Andréa Luciana Soares da Silva, Eduardo José Melo Dos Santos
The Major Histocompatibility Complex (MHC) harbors key genes of the immune response that are likely useful as biomarkers for infectious diseases. However, little is known about their microRNAs and what role they play in infections. The present study aimed to describe the miRNA genes in the MHC (MHC-miRNA), their variability and associations with infectious diseases. Additionally, MHC-miRNA host and target genes were also evaluated in associations with infectious diseases. Surveys in several databases and literature reviews identified 48 MHC-miRNA genes, with high SNP and CNV variability able to disrupt MHC-miRNA expression and putatively under selective pressure...
February 12, 2019: Human Immunology
Huaqiang Sun, Yeyong Zhang, Weiguo Song, Luxu Yin, Gongteng Wang, Dejia Yu, Qian Zhang, Xinfeng Yan, Shufeng Li
Synovial inflammation is observed in patients with osteoathritis (OA) and likely contributed to its exacerbation. Regulatory B (Breg) cells are shown to suppress inflammation in various diseases, including rheumatoid arthritis (RA). To examine whether Breg cells also participated in OA, we examined the synovial fluid from OA patients, and compared with that in RA patients. In OA synovial fluid, IL-10-producing B cells were present directly ex vivo and were increased upon stimulation, indicating that B cells were a source of IL-10 directly at the affected site of OA patients...
February 12, 2019: Human Immunology
Ashutosh Kumar, Kusum Harjai, Sanjay Chhibber
Enterobacterial pathogens that have acquired antibiotic resistance genes are a leading cause of community and hospital acquired infections. In such a situation vaccination is considered as a better option to prevent such infections. In the current study reverse vaccinology approach has been used to select peptides from already known immunogenic proteins to design a chimeric construct. We selected Yersiniabactin receptor of Escherichia coli UMN026 and Flagellin of Stenotrophomonas maltophila. B-cell linear epitopes were predicted using Bepipred prediction tool...
February 12, 2019: Human Immunology
Gonzalo Montero-Martín, Kalyan C Mallempati, Sridevi Gangavarapu, Francisco Sánchez-Gordo, Maria J Herrero-Mata, Antonio Balas, Jose L Vicario, Florentino Sánchez-García, Maria F González-Escribano, Manuel Muro, Maria R Moya-Quiles, Rafael González-Fernández, Javier G Ocejo-Vinyals, Luis Marín, Lisa E Creary, Kazutoyo Osoegawa, Tamara Vayntrub, Jose L Caro-Oleas, Carlos Vilches, Dolores Planelles, Marcelo A Fernández-Viña
Next-generation sequencing (NGS) at the HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1 and -DRB3/4/5 loci was performed on 282 healthy unrelated individuals from different major regions of Spain. High-resolution HLA genotypes defined by full sequencing of class I loci and extended coverage of class II loci were obtained to determine allele frequencies and also to estimate extended haplotype frequencies. HLA alleles were typed at the highest resolution level (4-field level, 4FL); with exception of a minor deviation in HLA-DPA1, no statistically significant deviations from expected Hardy Weinberg Equilibrium (HWE) proportions were observed for all other HLA loci...
February 11, 2019: Human Immunology
Maria Carmela Padula, Pietro Leccese, Nancy Lascaro, Teresa Carbone, Michele Gilio, Angela Anna Padula, Giuseppe Martelli, Salvatore D'Angelo
The endoplasmic reticulum aminopeptidase protein 1 gene (ERAP1) is related to several human diseases, including Behçet syndrome (BS), a multisystemic disorder with unknown etiology. ERAP1 is involved in immune response and its role can be influenced by gene single nucleotide variations (SNVs). We genotyped the ERAP1 whole structure in 50 consecutive BS patients and 50 ethnically-matched healthy controls using both bioinformatics and molecular methodologies. We identified two novel heterozygous missense SNVs of ERAP1 exon3 responsible for the p...
February 8, 2019: Human Immunology
Kazutoyo Osoegawa, Tamara A Vayntrub, Sabine Wenda, Dianne De Santis, Konstantinos Barsakis, Milena Ivanova, Susan Hsu, Jonathan Barone, Rhonda Holdsworth, Mary Diviney, Medhat Askar, Amanda Willis, Dawn Railton, Sophie Laflin, Ketevan Gendzekhadze, Arisa Oki, Nicoletta Sacchi, Michela Mazzocco, Marco Andreani, Reem Ameen, Catherine Stavropoulos-Giokas, Amalia Dinou, Margareth Torres, Rodrigo Dos Santos Francisco, Carles Serra-Pages, Damian Goodridge, Sandra Balladares, Maria P Bettinotti, Brian Iglehart, Zahra Kashi, Russell Martin, Chee Loong Saw, Ioannis Ragoussis, Jonathan Downing, Cristina Navarrete, Winnie Chong, Katsuyuki Saito, Martin Petrek, Stana Tokic, Karin Padros, Ma Beatriz Rodriguez, Viktoria Zakharova, Olga Shragina, Susana R Marino, Nicholas K Brown, Takashi Shiina, Shingo Suzuki, Eric Spierings, Qiuheng Zhang, Yuxin Yin, Gerald P Morris, Ana Hernandez, Phillip Ruiz, Seik-Soon Khor, Katsushi Tokunaga, Aviva Geretz, Rasmi Thomas, Fumiko Yamamoto, Kalyan C Mallempati, Sridevi Gangavarapu, Uma Kanga, Shweta Tyagi, Steven Ge Marsh, Will P Bultitude, Xiangjun Liu, Dajiang Cao, Maarten Penning, Carolyn K Hurley, Anne Cesbron, Claudia Mueller, Joannis Mytilineos, Eric Weimer, Mats Bengtsson, Gottfried Fischer, John A Hansen, Chia-Jung Chang, Steven J Mack, Lisa E Creary, Marcelo A Fernandez-Viña
The 17th International HLA and Immunogenetics Workshop (IHIW) organizers conducted a Pilot Study (PS) in which 13 laboratories (15 groups) participated to assess the performance of the various sequencing library preparation protocols, NGS platforms and software in use prior to the workshop. The organizers sent 50 cell lines to each of the 15 groups, scored the 15 independently generated sets of NGS HLA genotyping data, and generated "consensus" HLA genotypes for each of the 50 cell lines. Proficiency Testing (PT) was subsequently organized using four sets of 24 cell lines, selected from 48 of 50 PS cell lines, to validate the quality of NGS HLA typing data from the 34 participating IHIW laboratories...
February 6, 2019: Human Immunology
Cynthia Kramer, Sebastiaan Heidt, Frans Claas
Recent data suggest that HLA epitope matching is more predictive for the formation of donor specific antibodies (DSA) after transplantation than classical HLA antigen matching. A proper definition of the epitopes and their immunogenicity is crucial for a broad clinical application of epitope matching in solid organ transplantation. For that purpose, a novel epitope component was started during the 17th International Histocompatibility and Immunogenetics Workshop. Only a limited number of antibody data was available, resulting in a preliminary analysis confirming the potential relevance of epitope matching for the development of donor specific antibodies...
February 5, 2019: Human Immunology
Kazutoyo Osoegawa, Steven J Mack, Matthew Prestegaard, Marcelo A Fernández-Viña
The highly polymorphic classical human leukocyte antigen (HLA) genes display strong linkage disequilibrium (LD) that results in conserved multi-locus haplotypes. For unrelated individuals in defined populations, HLA haplotype frequencies can be estimated using the expectation-maximization (EM) method. Haplotypes can also be constructed using HLA allele segregation from nuclear families. It is straightforward to identify many HLA genotyping inconsistencies by visually reviewing HLA allele segregation in family members...
February 5, 2019: Human Immunology
Malini Raghavan, Brogan Yarzabek, Anita J Zaitouna, Sujatha Krishnakumar, Daniel S Ramon
HLA class I molecules are highly polymorphic cell surface proteins that trigger immune responses by CD8+ T cells and natural killer (NK) cells. Most humans express six different HLA class I proteins encoded by the HLA-A, HLA-B and HLA-C genes. HLA class I molecules bind to peptide antigens and present these antigens to T cell receptors (TCR) of CD8+ T cells. HLA class I expression levels also regulate NK cell activation. The presence of individual HLA class I genes is linked to many different disease, transplantation and therapy outcomes...
February 5, 2019: Human Immunology
Kirk D Wyatt, Richard J Bram
Advances in multi-agent chemotherapy and supportive care have dramatically improved survival of children with B-cell acute lymphoblastic leukemia (B-ALL); however, patients with relapsed and refractory disease continue to represent a therapeutic challenge. Hematopoietic stem cell transplant was the first immunotherapeutic approach to be used in the treatment of patients with relapsed or refractory disease. However, novel therapies such as bispecific antibodies that engage T-cells and chimeric antigen receptor T-cells (CAR-T) therapy have emerged as novel FDA-approved options that have the potential to become the new standard of care for these difficult-to-treat leukemias...
February 1, 2019: Human Immunology
Monal Sharma, S A Webber, A Zeevi, T Mohanakumar
Antibodies to HLA resulting in positive cytotoxicity crossmatch are generally considered a contraindication for cardiac transplantation. However, cardiac transplantations have been performed in children by reducing the Abs and modifying immunosuppression. To identify mechanisms leading to allograft acceptance in the presence of Abs to donor HLA, we analyzed priming events in endothelial cells (EC) by incubating with sera containing low levels of anti-HLA followed by saturating concentration of anti-HLA. Pre-transplant sera were obtained from children with low levels of Abs to HLA who underwent transplantation...
January 30, 2019: Human Immunology
B A González-Quezada, L E Creary, A J Munguia-Saldaña, H Flores-Aguilar, M A Fernández-Viña, C Gorodezky
The Mestizos of Oaxaca resulted from the admixture of Zapotecan Natives with Spaniards and Africans. We selected 112 donors from Oaxaca and applied next-generation sequencing to characterize exon and intron variants in complete or extended HLA genes. Some alleles found, are unique to Mexican Natives and most likely will be absent in most major ethnicities, namely: Caucasians, Africans or Asians. Among these are HLA-A*68:03:01, HLA-A*68:05:01, HLA-C*03:04:01:02, HLA-C*15:09, HLA-C*3:05, HLA-C*03:06:01, HLA-B*39:05:01, HLA-B*35:14:01, HLA-B*35:12:01, HLA-B*35:43:01, HLA-B*40:05, HLA-B:40:08, HLA-B*51:02:01, HLA-B*35:24:01 and HLA-B*39:08...
January 29, 2019: Human Immunology
Diana Iraíz Hernández-Zaragoza, Héctor Delgado-Aguirre, Rodrigo Barquera, Carmen Adalid-Sáinz, Stephen Clayton, Abraham Lona-Sánchez, Liliana González-Medina, Hanna Pacheco-Ubaldo, Alicia Bravo-Acevedo, Néstor Escareño-Montiel, Javier Morán-Martínez, Marisela Del Rocío González-Martínez, Yolanda Jaramillo-Rodríguez, Federico Juárez-de la Cruz, Joaquín Zúñiga, Edmond Yunis, Carolina Bekker-Méndez, Julio Granados
We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 453 Mexicans from the state of Zacatecas living in Zacatecas city (N = 84), Fresnillo (N = 103) and rural communities (N = 266) to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes for the state of Zacatecas include seven Native American most probable ancestry (A*02 ∼ B*39 ∼ DRB1*04 ∼ DQB1*03:02; A*02 ∼ B*35 ∼ DRB1*08 ∼ DQB1*04; A*24 ∼ B*39 ∼ DRB1*14 ∼ DQB1*03:01; A*02 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02; A*24 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02; A*68 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02 and A*24 ∼ B*35 ∼ DRB1*08 ∼ DQB1*04) and two European MPA haplotypes (HLA ∼ A*01 ∼ B*08 ∼ DRB1*03:01 ∼ DQB1*02 and A*29 ∼ B*44 ∼ DRB1*07 ∼ DQB1*02)...
January 24, 2019: Human Immunology
Qin Gu, Jun Chen, Yufeng Yao, Mingbo Sun, Li Shi
HLA-DRB1, -DQB1 and -DPB1 allele frequencies and estimated haplotype frequencies from 496 unrelated healthy Mongol subjects who living in Inner Mongolia Autonomous Region of China has been reported. HLA genes were genotyped using high-resolution sequence-based typing method. Chinese-Mongolian belongs to northern group of East Asians, but with its specific HLA-DRB1, DPB1 and DQB1 alleles and haplotypes characteristic.
January 24, 2019: Human Immunology
Andrea M Roca, Boris I Chobrutskiy, Blake M Callahan, George Blanck
Cervical cancer is more strongly associated with a specific virus, Human Papilloma Virus (HPV), in otherwise healthy individuals, than is any other cancer. Thus, there is an expectation that an adaptive immune signature of cervical cancer would be highly apparent. Here we used a genomics approach to investigate the relationship between T-cell receptor (TCR) V and J usage and survival for patients diagnosed with cervical cancer, relying exclusively on tissue and blood exome files. Specific TCR V or J segments, identified in recombination reads recovered from the exome files, were combined with the patient HLA alleles to identify V or J, HLA allele combination groups associated with distinct survival rates...
January 23, 2019: Human Immunology
Irini Evnouchidou, Peter van Endert
Presentation of short peptides, produced through intracellular proteolysis, by MHC class I molecules (MHC-I) is the basis of adaptive immune surveillance and responses by cytolytic CD8+ T lymphocytes. In the principal pathway of peptide processing for MHC-I that operates in all nucleated cells, MHC-I-binding peptides are produced through stepwise proteolysis starting with source protein degradation by cytosolic proteasome complexes. Among the fraction of proteasome products reaching the lumen of the endoplasmic reticulum, a significant proportion is thought to have a length exceeding that adapted to MHC class I binding and requires N-terminal trimming...
January 22, 2019: Human Immunology
Eric T Weimer, Karen Sherwood
We are pleased to introduce the new series in Human Immunology entitled "Point-Counterpoint." Within the field of HLA, there has been substantial change and evolution of technology that has greatly impacted the service HLA laboratories provide to providers and patients. Recently, ASHI staff sent out a survey to all ASHI Laboratory Directors with the goal of finding areas within Serology and Molecular HLA testing where laboratory practices differed among histocompatibility laboratories. The data from the survey will be made available to the ASHI community at-large through ASHI Quarterly...
January 21, 2019: Human Immunology
Qin Chen, Shunling Yuan, Hongwu Sun, Liusheng Peng
CD3+ CD20+ T cells are a population of CD3+ T cells co-expressing CD20 that make up to ∼3-5% of the CD3+ T-cell compartment in the peripheral blood of human beings. In healthy individuals, CD3+ CD20+ T cells are heterogeneous for containing a lower proportion of CD4+ cells, but produce higher levels of IL-17A and/or IFN-γ than those of CD3+ CD20- T cells. Recently, emerging studies have shown a pathogenic behavior of CD3+ CD20+ T cells in autoimmune diseases and CD20+ T-cell malignancies, and patients with the diseases may benefit from anti-CD20 immunotherapy to deplete these cells...
January 10, 2019: Human Immunology
Maike Janssen, Friedrich Thaiss, Björn Nashan, Martina Koch, Hansjörg Thude
Human leucocyte antigen G (HLA-G) is a non-classical HLA-class I antigen that exerts immunoregulatory functions. The polymorphisms 14-base pair (bp) insertion/deletion (ins/del) (rs1704) and +3142C>G (rs1063320) could modify the expression level of HLA-G. We genotyped 175 kidney recipients (41 with acute rejection and 134 without rejection) and additionally the corresponding donors for both polymorphisms in order to assess their impact on acute rejections one year after transplantation. In addition, we analyzed soluble HLA-G (sHLA-G) levels in sera of 32 living kidney donors and compared the sHLA-G levels in terms of the present genotype...
January 2, 2019: Human Immunology
Saeideh Jamali, Abdolfatah Sarafnejad, Pedram Ahmadpoor, Mohsen Nafar, Mozhdeh Karimi, Atefeh Eteghadi, Mir Saeed Yekaninejad, Ali Akbar Amirzargar
BACKGROUND: Accumulating evidence suggests that regulatory T cells (Tregs) have a crucial role in immune tolerance and long-term graft survival. However, the influence of immunosuppressive drugs on the level of Tregs has not been fully understood. Therefore we prospectively compare the effect of two different calcineurin inhibitor (CNI)-based immunosuppression protocols on Tregs frequencies and expression of regulatory and effector T cell-related genes in renal transplant recipients. METHODS: The study included 24 renal transplant recipients who received induction therapy (Antithymocyte globulin) and were on triple immunosuppressive therapy so that one group was on Tacrolimus (Tac), mycophenolate moftile (MMF) and prednisolone (P) whereas another group was on Tac, Sirolimus (SRL) and P...
December 28, 2018: Human Immunology
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