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Human Immunology

John D Scandling, Stephan Busque, Robert Lowsky, Judith Shizuru, Asha Shori, Edgar Engleman, Kent Jensen, Samuel Strober
Current theory holds that macrochimerism is essential to the development of transplant tolerance. Hematopoietic cell transplantation from the solid organ donor is necessary to achieve macrochimerism. Over the last 10 to 20 years, trials of tolerance induction with combined kidney and hematopoietic cell transplantation have moved from the preclinical to the clinical arena. The achievement of macrochimerism in the clinical setting is challenging, and potentially toxic due to the conditioning regimen necessary to hematopoietic cell transplantation and due to the risk of graft-versus-host disease...
January 9, 2018: Human Immunology
Ajay K Baranwal, Sanjeev Goswami, Deepali K Bhat, Gurvinder Kaur, Sanjay K Agarwal, Narinder K Mehra
BACKGROUND: Since soluble isoforms of MICA play an important role in modulating the immune response, we evaluated a possible correlation between their levels and development of acute rejection following renal transplantation. METHODS: Serum samples collected at pre- and different time points posttransplant from 137 live related donor renal transplant recipients were evaluated retrospectively for sMICA levels and for the presence of MICA antibodies. Samples from 30 healthy volunteers were also tested as controls...
January 9, 2018: Human Immunology
Saeed Aslani, Soheila Sobhani, Farhad Gharibdoost, Ahmadreza Jamshidi, Mahdi Mahmoudi
The pathogenesis of many diseases is influenced by environmental factors which can affect human genome and be inherited from generation to generation. Adverse environmental stimuli are recognized through the epigenetic regulatory complex, leading to gene expression alteration, which in turn culminates in disease outcomes. Three epigenetic regulatory mechanisms modulate the manifestation of a gene, namely DNA methylation, histone changes, and microRNAs. Both epigenetics and genetics have been implicated in the pathogenesis of systemic sclerosis (SSc) disease...
January 9, 2018: Human Immunology
Satoru Todo, Kenichiro Yamashita
Liver transplantation is accepted as the most reliable therapeutic option for patients with end-stage liver failure, but lifelong administration of immunosuppressive agents continues to be problematic due to various drug-induced morbidities and the risk of mortality. Complete cessation of immunosuppressive drugs while maintaining normal graft function and histology, called operational tolerance, has the potential to overcome these long-standing problems. Previously, we reported the results of a pilot study of anti- donor regulatory T cell therapy in 10 consecutive adult patients who underwent living donor liver transplantation (LDLT), of whom 7 patients successfully stopped immunosuppression for nearly 2 years...
December 29, 2017: Human Immunology
Howard W Wiener, Sadeep Shrestha, Hailin Lu, Etienne Karita, William Kilembe, Susan Allen, Eric Hunter, Paul A Goepfert, Jianming Tang
Immune control of HIV-1 infection depends heavily on cytotoxic T-lymphocyte responses restricted by diverse HLA class I molecules. Recent work has uncovered specific amino acid residues (AARs) that seem to dictate the extent of immune control in African Americans, which prompted us to test these emerging hypotheses in seroconverters (SCs) from southern and eastern Africa. Based on data from 196 Zambians and 76 Rwandans with fully resolved HLA alleles and pre-therapy HIV-1 viral loads (VL) in the first 3- to 36-month of infection (>2,300 person-visits), four AARs of primary interest (positions 63, 97, 116 and 245 in the mature HLA-B protein) were found to explain 8...
December 28, 2017: Human Immunology
Megan Sykes
This review focuses on mechanistic studies performed in recipients of non-myeloablative bone marrow transplant regimens developed at Massachusetts General Hospital in HLA-identical and HLA-mismatched haploidentical combinations, initially as a platform for treatment of hematologic malignancies with immunotherapy in the form of donor leukocyte infusions, and later in combination with donor kidney transplantation for the induction of allograft tolerance. These studies point to a prominent early role for regulatory T cells in tolerance induction, followed by partial and gradual deletion of donor-reactive T cells...
December 28, 2017: Human Immunology
Alba Grifoni, Daniela Weiskopf, Cecilia S Lindestam Arlehamn, Michael Angelo, Shay Leary, John Sidney, April Frazier, Elizabeth Phillips, Simon Mallal, Steven J Mack, Rashmi Tippalagama, Suraj Goonewardana, Sunil Premawansa, Gayani Premawansa, Ananda Wijewickrama, Aruna D De Silva, Alessandro Sette
DNA sequence-based typing at the HLA-A, -B, -C, -DPB1, -DQA1, -DQB1, and -DRB1 loci was performed on 714 healthy adult blood bank donors from Colombo, Sri Lanka, to characterize allele frequencies in support of studies on T cell immunity against pathogens, including Dengue virus. Deviations from Hardy Weinberg proportions were not detected at any locus. Several alleles were found in more than 30% of individuals, including the class II alleles DPB1∗04:01, DPB1∗02:01, DQB1∗06:01 and DRB1∗07:01, and the class I alleles A∗33:03 and A∗24:02...
December 28, 2017: Human Immunology
David Forner, Robert Liwski, Ian Alwayn
BACKGROUND: The impact of human leukocyte antigen (HLA) matching on outcomes in liver transplantation is controversial. Varying levels of HLA matching resolutions were examined in a uniform patient population with no pre-transplant DSA from a small, single center cohort. METHODS: Retrospective chart review from a single center yielded 131 patients, 67 of which were confirmed to be DSA negative, all of which received induction immunotherapy and post-operative immunosuppression...
December 28, 2017: Human Immunology
Reem Ameen, Salem Al Shemmari, Medhat Askar
The frequency of HLA genes in one population may not accurately represent frequencies in other populations. In this study, we characterized extended human leukocyte antigen (HLA) haplotypes in several families of Kuwaiti descent by high-resolution typing using next-generation technology. A total 81 members (including patients and related donors) from 21 families were enrolled. No haplotypes were shared among multiple families. Of 77 haplotypes identified, 23 were not listed in the HaploStats database. Two haplotypes were most common in African Americans, six in Asian Pacific Islanders, three in Caucasians, three in Hispanics, and three in Native Americans...
December 28, 2017: Human Immunology
Kento Kawai, Masateru Uchiyama, Joanna Hester, Kathryn Wood, Fadi Issa
Regulatory T cells (Tregs) are critical mediators of immune homeostasis and hold significant promise in the quest for transplantation tolerance. Progress has now reached a critical threshold as techniques for production of clinical therapies are optimised and Phase I/II clinical trials are in full swing. Initial safety and efficacy data are being reported, with trials assessing a number of different strategies for the introduction of Treg therapy. It is now more crucial than ever to elucidate further the function and behaviour of Tregsin vivoand ensure safe delivery...
December 27, 2017: Human Immunology
Federica Casiraghi, Norberto Perico, Giuseppe Remuzzi
The primary challenge in organ transplantation continues to be the need to suppress the host immune system long-term to ensure prolonged allograft survival. Long-term non-specific immunosuppression can, however, result in life-threatening complications. Thus, efforts have been pursued to explore novel strategies that would allow minimization of maintenance immunosuppression, eventually leading to transplant tolerance. In this scenario, bone marrow-derived mesenchymal stromal cells (MSC), given their given unique immunomodulatory properties to skew the balance between regulatory and memory T cells, have emerged as potential candidates for cell-based therapy to promote immune tolerance...
December 27, 2017: Human Immunology
Ali H Ad'hiah, Zahra'a A Ahmed, Milad A Al-Naseri, Ehab D Salman, Osama B Al-Saffar, Hiba S Ahmed, Talib A Hussain, Ekhlass M Idan, Ibtesam B Hassan, Batool A Shihab, Lateef O Mohammed, Fatima S Al-Nasiri
In this report, 224 unrelated healthy Iraqi Arabs (102 males and 122 females) were genotyped for 22 SNPs (single nucleotide polymorphisms) belong to 13 cytokine genes (IL1A, IL1B, IL1RA, IL1R, IL2, IL4, IL4R, IL6, IL10, IL12, IFNG, TNFA and TGFB1). The method of detection was PCR-SSP (polymerase chain reaction-sequence specific primer). The data were presented in terms of allele and genotype frequencies. Two-locus haplotype frequencies were also estimated for some SNPs. Genotype frequencies of detected cytokine gene polymorphisms are available in the Database of Allele Frequencies Net under the AFND number 3422 and the population name "Iraq Arab Cytokine"...
December 27, 2017: Human Immunology
Chia-Jung Chang, Kazutoyo Osoegawa, Robert P Milius, Martin Maiers, Wenzhong Xiao, Marcelo Fernandez-Viňa, Steven J Mack
For over 50 years, the International HLA and Immunogenetics Workshops (IHIW) have advanced the fields of histocompatibility and immunogenetics (H&I) via community sharing of technology, experience and reagents, and the establishment of ongoing collaborative projects. Held in the fall of 2017, the 17th IHIW focused on the application of next generation sequencing (NGS) technologies for clinical and research goals in the H&I fields. NGS technologies have the potential to allow dramatic insights and advances in these fields, but the scope and sheer quantity of data associated with NGS raise challenges for their analysis, collection, exchange and storage...
December 13, 2017: Human Immunology
Meri Kirijas, Sonja Genadieva Stavrik, Aleksandar Senev, Olivija Efinska Mladenovska, Aleksandar Petlichkovski
AIM: The aim of this study was to determine HLA allele and 2-, 3- and 4-loci haplotype frequencies in a sample from Macedonian population with defined haplotypes based on family history. MATERIAL AND METHODS: We analysed 286 unrelated individuals with Macedonian origin, parents of patients who needed stem cell transplantation, in the period of 01.01.2003 till 31.12.2016. Allele and haplotype frequencies, as well as Hardy-Weinberg equilibrium were calculated using the Arlequin3...
December 7, 2017: Human Immunology
Antonio Arnaiz-Villena, Jose Palacio-Gruber, Mercedes Enriquez de Salamanca, Ignacio Juárez, Cristina Campos, Jorge Nuñez, Ester Muñiz, Jose Manuel Martin-Villa
HLA-G and HLA-A frequencies have been analysed in Amerindians from Ecuador. HLA-G allele frequencies are found to be closer to those of other Amerindians (Mayas from Guatemala and Uros from Peru) and closer to European ones than to Far East Asians groups, particularly, regarding to HLA-G∗ 01:04 allele. HLA-G/-A haplotypes have been calculated for the first time in Amerindians. It is remarkable that HLA-G∗01:05N "null" allele is found in a very low frequency (like in Amerindian Mayas and Uros) and is also found in haplotypes belonging to the HLA-A19 group of alleles (HLA-A∗30, -A∗31,-A∗33)...
December 4, 2017: Human Immunology
Sunil Daga, Harry Moyse, David Briggs, David Lowe, Neil Evans, James Jones, Rico Buchli, Curtis McMurtrey, Arend Mulder, William Hildebrand, Frans Claas, Robert Higgins, Daniel A Mitchell, Daniel Zehnder
No abstract text is available yet for this article.
December 4, 2017: Human Immunology
Leonardo Maldaner Amorim, Hoang van Tong, Nghiem Xuan Hoan, Luciana de Brito Vargas, Enilze Maria de Souza Fonseca Ribeiro, Maria Luiza Petzl-Erler, Angelica B W Boldt, Nguyen Linh Toan, Le Huu Song, Thirumalaisamy P Velavan, Danillo G Augusto
The KIR (killer cell immunoglobulin-like receptors) gene family codifies a group of receptors that recognize human leukocyte antigen (HLA) molecules and modulate natural killer (NK) cells response. Genetic diversity of KIR genes and HLA ligands has not yet been deeply investigated in South East Asia. Here, we characterized KIR gene presence/absence polymorphism of 14 KIR genes and two pseudogenes, as well as the frequencies of the ligands HLA-Bw4, HLA-C1 and HLA-C2 in a Vietnamese population from Hanoi (n=140)...
November 27, 2017: Human Immunology
Andrzej Wiśniewski, Łukasz Matusiak, Aneta Szczerkowska-Dobosz, Izabela Nowak, Wioleta Łuszczek, Piotr Kuśnierczyk
The aim of this case-control study was to elucidate the role of some single nucleotide polymorphisms (SNPs) in the ERAP1 (rs27524, rs27044, rs30187, rs2287987 and rs26653) and ERAP2 (rs2248374) genes in predicting the risk for psoriasis vulgaris in the Polish population. ERAP1, ERAP2 and HLA-C∗06:02 typing was done using the TaqMan SNP genotyping assays. We confirmed a strong association of the HLA-C∗06:02 allele with early-onset psoriasis. In ERAP1, rs30187T increased the risk of psoriasis in HLA-C∗06:02-positive patients, most strongly in late onset psoriasis, whereas it was protective when the HLA-C∗06:02 allele was absent...
November 25, 2017: Human Immunology
Lilian O Guimarães, Miklos Maximiliano Bajay, Eliana F Monteiro, Gerhard Wunderlich, Sidney E Santos, Karin Kirchgatter
The innate immune system governed by toll-like receptors (TLRs) provides the first line of defense against pathogens. Surface-localized TLR1 and TLR6 are known to detect parasite components. TLR encoding genes were shown to display signatures of recent positive selection in Europeans and might be involved in local adaptation at immune-related genes. To verify the influence of Brazilian population admixture on the distribution of polymorphisms in TLRs, we analyzed the genotype frequencies of 24 polymorphisms distributed across five TLR genes in a Southeastern Brazilian population where autochthonous cases of malaria occur in small foci of transmission...
November 23, 2017: Human Immunology
Hajime Sasaki, Tetsu Oura, Thomas R Spitzer, Yi-Bin Chen, Joren C Madsen, James Allan, David H Sachs, A B Cosimi, Tatsuo Kawai
Based upon observations in murine models, we have developed protocols to induce renal allograft tolerance by combined kidney and bone marrow transplantation (CKBMT) in non-human primates (NHP) and in humans. Induction of persistent mixed chimerism has proved to be extremely difficult in major histocompatibility complex (MHC)-mismatched primates, with detectable chimerism typically disappearing within 30-60 days. Nevertheless, in MHC mismatched NHP, long-term immunosuppression-free renal allograft survival has been achieved reproducibly, using a non-myeloablative conditioning approach that has also been successfully extended to human kidney transplant recipients...
November 21, 2017: Human Immunology
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