共查询到20条相似文献,搜索用时 328 毫秒
1.
Manish J. Gandhi Deborah Ferriola Curt Lind Jamie L. Duke Anh Huynh Anna Papazoglou Kate Mackiewicz Mette Christiansen Wei Dong Susan Hsu Dawn Thomas Brittany Schneider Erin Pierce Jane Kearns Malek Kamoun Dimitri Monos Medhat Askar 《Human immunology》2017,78(10):642-648
Background
A simplified protocol for HLA-typing -by NGS, developed for use with the Illumina MiSeq, was performed by technologists with varying NGS experience to assess accuracy and reproducibility.Methods
Technologists from six laboratories typed the same 16 samples at HLA-A, B, C, DRB1, and DQB1. The protocol includes long range PCR, library preparation, and paired-end 250 bp sequencing. Two indexing strategies were employed: locus-specific indexing whereby each locus was tagged uniquely and sample-specific indexing whereby all 5 loci for a sample were pooled prior to library preparation. Sequence analysis was performed with two software packages, Target HLA (Omixon) and NGSengine (GenDx).Results
The average number of sequence reads per library was 387,813; however, analysis was limited to 40,000 reads for locus-indexed libraries and 200,000 reads for sample-indexed libraries resulting in an average depth of coverage of 1444 reads per locus. Sufficient reads for genotype analysis were obtained for 98.4% of libraries. Genotype accuracy was >97% in pooled amplicons and >99% in individual amplicons by both software analysis. Inter-laboratory reproducibility was 99.7% and only cause of discordance was cross-contamination of a single amplicon.Conclusions
This NGS HLA-typing protocol is simple, reproducible, scalable, highly accurate and amenable to clinical testing. 相似文献2.
Daniel S. Ramon Yihung Huang Lili Zhao TrisAnn Rendulic Jeong M. Park Randall S. Sung Milagros Samaniego 《Human immunology》2017,78(2):57-63
Background
The Luminex® single antigen bead assay (SAB) is the method of choice for monitoring the treatment for antibody-mediated rejection (AMR). A ?50% reduction of the dominant donor-specific antibody (IgG-DSA) mean fluorescence intensity (MFI) has been associated with improved kidney allograft survival, and C1q-fixing DSA activity is associated with poor outcomes in patients with AMR. We aimed to investigate if C1q-DSA can be used as a reliable predictor of response to therapy and allograft survival in patients with biopsy-proven AMR.Methods
We tested pre- and post-treatment sera of 30 kidney transplant patients receiving plasmapheresis and low-dose IVIG for biopsy-proven AMR. IgG-DSA and C1q-DSA MFI were measured and correlated with graft loss or survival. Patients were classified as nonresponders (NR) when treatment resulted in <50% reduction in MFI of IgG-DSA and/or C1q-DSA was detectable following therapy.Results
Differences in the percentage of patients deemed NR depended upon the end-point criterion (73% by reduction in IgG-DSA MFI vs. 50% by persistent C1q-DSA activity). None of the seven patients with <50% reduction of IgG-DSA but non-detectable C1q-DSA-fixing activity after therapy experienced graft loss, suggesting that C1q-DSA activity may better correlate with response. Reduction of C1q-DSA activity predicted graft survival better than IgG-DSA in the univariate Cox analysis (20.1% vs. 5.9% in NR; log-rank P-value = 0.0147).Conclusions
A rapid reduction of DSA concentration below the threshold required for complement activation is associated with better graft survival, and C1q-DSA is a better predictor of outcomes than IgG-DSA MFI reduction. 相似文献3.
Guillaume Claisse Lena Absi Fabrice Cognasse Eric Alamartine Christophe Mariat Nicolas Maillard 《Human immunology》2017,78(4):336-341
Background
Complement-binding assays are proposed to better stratify the risk of antibody-mediated rejection associated-graft failure. Despite promising clinical results, some have suggested that the MFI of anti-HLA antibodies may influence these tests.Methods
We investigated the impact of Abs MFI reduction, induced by plasmapheresis, on C1q- and C3d-binding assays. Sera provided from 7 sensitized kidney transplant patients were analyzed.Results
Four hundreds and thirty-three SABs were analyzed. Before plasmapheresis, when compared to C1q? SABs, C1q+ SABs had a higher median MFI [17397 (IQR: 14851–18794) vs. 2745 (IQR: 1125–6476), p < 0.01]. SABs that remained C1q+ after plasmapheresis had a higher median MFI. Regarding the C3d assay, results were strictly comparable. MFI value was a powerful predictor of both C1q and C3d positivity [AUC 0.97 (CI95% 0.95–0.99) and 0.96, (CI95% 0.93–0.98), respectively].Conclusion
Our data suggest that both C1q- and C3d-binding assays are intimately linked to the MFI of anti-HLA Abs. 相似文献4.
Smriti Kanangat Christopher W. Seder Melissa R. Pergande Gabriela C. Lobato Cristina L. Fhied Maryam F. Raouf Michael J. Liptay Jeffrey A. Borgia 《Human immunology》2018,79(7):558-563
Background
This study explores the potential diagnostic utility of soluble Human Leukocyte Antigen (sHLA) molecules differentially released by lung adenocarcinoma and benign lung lesions.Methods
Conditioned media from the NSCLC cell lines H358 and H1703 were immunoblotted for soluble isoforms of major histocompatibility complex (MHC) class I (ABC) and II (DRB1, DMB, and DQ) antigens. Sera from 25 patients with benign and 25 patients with malignant lesions were similarly evaluated to appraise the potential diagnostic value.Results
Higher concentrations of soluble HLA class I molecules were observed in conditioned medium for the highly-invasive H1703 cell line, relative to the more indolent H358 cells. Evaluation of these markers against a cohort of 50 cases demonstrated that patients with malignant lesions possess higher levels of HLA class I and II molecules relative to those with benign lesions (p?<?0.05), with exception to the primary isoform, DQA1, which was suppressed in malignancies. An analysis of biomarker performance via ROC analysis revealed promising performance (AUC?>?0.75) for DMB and the 26?kDa isoform of DQ in distinguishing lesion pathology.Conclusions
Soluble HLA molecules may have diagnostic value for early-stage NSCLC. Validation studies are currently underway using sera from a lung cancer screening cohort. 相似文献5.
Mary Ann Lim Matthew Palmer Jennifer Trofe-Clark Roy D Bloom Annette Jackson Mary Carmelle Philogene Malek Kamoun 《Human immunology》2017,78(4):350-356
Objective
To determine the association of antibodies against angiotensin II type 1 receptor (AT1R Ab) and histopathologic changes seen in patients with kidney allograft rejection and negative donor specific HLA antibodies (DSA).Methods
Stored sera from 27 patients who had biopsy-proven rejection in the absence of DSA were tested for AT1R Ab. Biopsy slides of all patients were re-examined and classified according to Banff 2013 criteria. Histopathologic changes were compared between AT1R positive and negative patients.Results
75% of patients with positive pre-transplant AT1R Ab had antibody mediated rejection (AMR) compared to 37% of AT1R Ab-negative patients. A trend towards increased interstitial inflammation was observed in the AT1R Ab positive group (p = 0.08). More patients in the AT1R Ab positive group had microcirculation inflammation (88% vs 58% with glomerulitis scores ≥1; 75% vs 58% with peritubular capillaritis scores ≥1).Conclusion
In kidney transplant recipients with rejection and no DSA, a higher incidence of AMR and worse inflammation scores are observed in the presence of positive pre-transplant AT1R antibodies. 相似文献6.
Stephen P. Persaud Brian Duffy Donna L. Phelan Thalachallour Mohanakumar Rowena Delos Santos Joseph P. Gaut Chang Liu 《Human immunology》2017,78(11-12):692-698
Objectives
To investigate immunological mechanisms underlying accelerated antibody-mediated rejection (AMR) of a living-related renal allograft in a patient with no detectable antibodies to donor human leukocyte antigens (HLA) in pre-transplant sera.Methods
Pre- and post-transplant HLA antibody specificities were determined by single-antigen bead assay, and crossmatching was performed by flow cytometry- and complement-dependent cytotoxicity-based methods. Intermediate- and high-resolution HLA typing were performed by molecular methods.Results
Pre-transplant patient serum reacted weakly against Bw6-positive beads; cytotoxicity and flow crossmatches were negative. The patient was mismatched for the donor antigens B62 and C10 (Bw6-positive). Following transplantation, strong antibody responses against B62, C10, and all Bw6-positive beads were detected. This reactivity was initially masked by complement interference, but became apparent at 1:20 dilution. High-resolution typing suggested that the anti-C16 antibody reactivity detected was an allele-specific response to donor C116:01 (Bw6-positive) but not recipient C116:02 (Bw6-negative). Alloimmunization likely occurred during pregnancy, during which HLA-C14 (Bw6-positive) was the only mismatched paternal HLA Class I allele.Conclusions
Sensitization to HLA-Bw6 via exposure to paternal HLA-C14 during pregnancy likely predisposed this patient to AMR. The case demonstrates the immunogenicity of HLA-C14-associated Bw6 epitopes in vivo and the clinical significance of low-level antibodies to HLA-Bw6. 相似文献7.
Marcela Caleffi da Costa Lima Caniatti Sueli Donizete Borelli Ana Lúcia Falavigna Guilherme Soraya Barrionuevo Franzener Luiza Tamie Tsuneto 《Human immunology》2018,79(1):51-56
Background
Killer cell immunoglobulin-like receptors (KIRs), found on the surface of natural killer (NK) cells, play a key role in controlling the innate response. Such response depends on a series of cellular interactions between these receptors and HLA activating/inhibiting ligands. Atopic diseases have been associated with genes that regulate cytokine production and HLA genes, which may either protect or predispose to hypersensitivity.Objective
To verify an association study of KIR genes with sensitization to the following mites: Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Blomia tropicalis.Methods
A total of 341 children aged up to 14?years, were classified as mite-sensitive or mite-insensitive after undergoing a skin prick test for immediate allergic reactions. The presence/absence of KIR genes and their human leukocyte antigen (HLA) ligands was determined by polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) with the commercial kit LabType? using Luminex?.Results
The frequencies of KIR genes and their respective class I HLA ligands and the frequency of haplotypes were performed in sensitive and insensitive individuals, and no significant differences were found.Conclusion
Our results suggest no influence of KIR genes on resistance/susceptibility to sensitization to dust mites. 相似文献8.
《Human immunology》2022,83(5):467-475
Complement dependent cytotoxicity crossmatch (CDC-XM) has been the original standard crossmatch test, whereas, flow cytometry crossmatch (FCXM) is an enhanced and highly sensitive crossmatch assay performed to detect donor specific anti-HLA antibodies (DSA). We analyzed American Society for Histocompatibility and Immunogenetics (ASHI) proficiency testing data (2011–2020) and examined the number of laboratories performing CDC-XM vs. FCXM, the overall efficiency of laboratories in reporting ≥80% consensus CDC-XM vs. FCXM result, and reasons for non-consensus results in the two assays. Of 600 crossmatches in each crossmatch category, the percentage of laboratories reporting T cell CDC-XMs reduced from 40% in 2011 to 13% in 2020, T cell anti-human globulin (AHG) CDC-XM reduced from 56% in 2011 to 21% in 2020, and B cell CDC-XM reduced from 51% in 2011 to 20% in 2020. The percentage of laboratories performing T cell and B cell FCXM remained at approximately 80% throughout. CDC-XM performed on par with FCXM in providing a consensus negative result using negative DSA serum, but under-performed in comparison to FCXM in providing a consensus positive result using positive DSA serum. In addition, only minority of CDC-XMs was reported positive in presence of complement fixing DSA. This study shows that non-consensus CDC-XM was always in presence of HLA IgG DSA and that laboratories may be struggling to interpret the low sensitive CDC-XM results, where highly sensitive solid phase multi-antigen or single antigen assay shows the presence of HLA IgG DSA in serum. 相似文献
9.
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. HLA typing was achieved by sequence specific oligonucleotide probe (SSOP) method using LABType® kits. Eplet mismatch analysis was conducted using HLAMatchMaker software.Results
The mean number of HLA-A antigen mismatches was significantly higher in patients experiencing acute rejection (1.8 vs 1.6, p?=?0.006). Rejection patients more frequently possessed two HLA-A mismatches compared to their non-rejection counterparts (77% vs 43%, p?=?0.071). Patient survival was found to be non-significantly decreased in patients with a higher eplet mismatch load at the HLA-A locus (p?=?0.155). No other loci were found to be predictive.Conclusion
In conclusion, HLA mismatches were found to increase acute rejection and be associated with decreased patient survival. The outcomes of this study suggest an involvement of HLA-A locus mismatches in predicting liver transplant rejection and patient survival. 相似文献10.
11.
Georg A. Böhmig Samantha Fidler Frank T. Christiansen Gottfried Fischer Paolo Ferrari 《Human immunology》2013
An independent pool of 16 incompatible live donor–recipient pairs registered at the Vienna transplant unit was applied to test whether virtual crossmatch allocation used in the Australian kidney paired donation (KPD) program reliably predicts negative crossmatches. High resolution HLA data were entered into the computer-matching algorithm and allocation was performed excluding any DSA > 2000MFI. CDC and flow crossmatch data of recipients against any of the donors were available for 112 crossmatch combinations. The computer program identified 19 possible pairings in 2-way or 3-way chains in multiple combinations. The top ranked combination included one 3-way and two 2-way ABO-compatible chains. Where crossmatches were available all recipients were CDC crossmatch negative with the computer-matched donor. Excluding allocation of KPD donors in the presence of DSA > 2000MFI had a negative predictive of 99.9% for CDC and 96.4% for flow crossmatch. In the 12 pairings with ?1 DSA against crossmatched donors there was a negative CDC and flow crossmatch. These results show excellent correlation between matching using virtual crossmatch and actual crossmatch results. Using the 2000MFI cut-off the number of potentially unacceptable CDC and flow crossmatch positive pairings identified by virtual crossmatching is low, but some potential crossmatch negative pairings are missed. 相似文献
12.
Ajay K. Baranwal Sanjeev Goswami Deepali K. Bhat Gurvinder Kaur Sanjay K. Agarwal Narinder K. Mehra 《Human immunology》2018,79(3):160-165
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 post-transplant 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.Results
Significantly higher levels of sMICA were observed in the pretransplant sera of allograft recipients as compared to healthy controls. Patients with acute cellular rejection experienced a significant fall in their levels at the time of diagnosis as compared to their pretransplant values and posttransplant follow up time points (p?=?.01, .003, .005 and .04 respectively at pre vs biopsy (Bx), POD7 vs Bx, POD 30 vs Bx, POD 90 vs Bx). However, no such difference was noted in patients undergoing antibody mediated rejection. Further the study did not reveal any correlation on the presence/absence of MICA antibodies with either an increase or decrease in sMICA levels.Conclusions
Estimating circulating levels of soluble MICA could provide useful information of prognostic importance in assessing graft outcome following renal transplantation. 相似文献13.
Meri Kirijas Sonja Genadieva Stavrik Aleksandar Senev Olivija Efinska Mladenovska Aleksandar Petlichkovski 《Human immunology》2018,79(3):145-153
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 Arlequin3.5 software. Population comparison was calculated using the PHYLIP software.Results
We identified 18 HLA-A, 26 HLA-B, 13 HLA-C and 13 HLA-DRB1 allele group families. The most frequent allele groups in our population were HLA-A*02 (29.0%), HLA-A*24 (13.8%), HLA-B*35 (16.1%), HLA-B*51 (14.7%), HLA-B*18 (14.7%), HLA-C*07 (27.9%), HLA-DRB1*11 (25.5%) and HLA-DRB1*16 (14.8%). The most frequent four loci haplotype was HLA-A*01-B*08-C*07-DRB1*03 (2.7%). Our comparison showed that the Macedonian population is closely related to the neighbouring countries in the Balkan Peninsula.Conclusion
This study provides data about the HLA diversity in the Macedonian population, which can be very important in the process of unrelated donor search, and in addition yields control group for future disease association studies in our population. 相似文献14.
Background
Knee osteoarthritis has a lifetime risk of nearly one in two, with obese individuals being most susceptible. While exercise is universally recognized as a critical component for management, unsafe or ineffective exercise frequently leads to exacerbation of joint symptoms.Aim
Evaluate the effect of a 12 week lower body positive pressure (LBPP) supported low-load treadmill walking program on knee pain, joint function, and performance of daily activities in patients with knee osteoarthritis (OA).Design
Prospective, observational, repeated measures investigation.Setting
Community based, multidisciplinary musculoskeletal medicine clinic.Patients
Thirty-one patients, aged 50–75, with a BMI ≥ 25 kg/m2 and radiographic confirmed mild to moderate knee OA.Intervention
Twelve week LBPP treadmill walking exercise regimen.Outcome measures
The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Canadian Occupational Performance Measure (COPM) were used to quantify joint symptoms and patient function; isokinetic thigh muscle strength was evaluated; and a 10-point VAS was used to quantify acute knee pain while walking. Baseline and follow-up data were compared in order to examine the effect of the 12 week exercise intervention.Results
There was a significant difference between baseline and follow-up data: KOOS and COPM scores both improved; thigh muscle strength increased; and acute knee pain during full weight bearing walking diminished significantly.Conclusions
Participation in a 12 week LBPP supported treadmill walking exercise regimen significantly enhanced patient function and quality of life, as well as the ability to perform activities of daily living that patient's self-identified as being important, yet difficult to perform. 相似文献15.
P. Veerus R. Kullaste K. Pungas T. Aavik K. Lang 《Transfusion Clinique et Biologique》2017,24(4):404-409
Background
Donating blood in Estonia is non-remunerated and voluntary. Estonian Blood Service system has four independent regional blood centres that are responsible for blood collection, processing, screening and distribution of blood components to hospitals for clinical use.Study design
This research was carried out as a questionnaire survey. A questionnaire was developed to study lapsing first time donors’ (FTD) blood donation experience, intention and willingness to donate again.Methods
A thousand five hundred and forty-six questionnaires were posted to donors who had one successful donation in 2010 and who had not returned to second donation till the year 2012. For data analysis routine statistical methods were used. To evaluate the most appropriate number of classes, based on previous experience and future expectations, latent class analysis was used.Results
There were 453 respondents (29.3%). For the majority of aspects of blood donation experience the emotions were positive. Results of the study suggested that blood collection agencies should intervene to bolster donors’ attitudes, perceived control, and identity as a donor during this crucial post-first donation period.Conclusion
First blood donation seems to have been a positive experience. Reasons leading to stopping blood donation should be studied further. Establishing a donor registry for Estonia would be essential to keep track of donors. 相似文献16.
Patricia Cristina Grenzi Érika Fernandes Campos Hélio Tedesco-Silva Claudia Rosso Felipe Maria Fernanda Soares José Medina-Pestana Hinrich Peter Hansen Maria Gerbase-DeLima 《Human immunology》2018,79(7):550-557
Background
Soluble CD30 (sCD30) is a suggested marker for kidney transplantation outcomes. We investigated whether sCD30 serum levels are influenced by immunosuppression and whether they correlate with findings in protocol biopsies and with CD30 gene expression in peripheral blood mononuclear cells (PBMC).Methods
We studied 118 kidney transplant recipients that initially received tacrolimus (TAC) and, at month-3, were converted or not to sirolimus (SRL).Results
sCD30 serum levels gradually declined after transplantation, being the decline more pronounced in the SRL group. CD30 gene expression in PBMC was higher in the SRL group than in the TAC group. Patients with IF/TA?≥?I in the month-24 protocol biopsy had higher sCD30 levels than patients without IF/TA, in the SRL group (P?=?.03) and in the TAC group (P?=?.07). CD30+ cells were observed in three out of 10 biopsies with inflammatory infiltrate from the SRL group. In mixed lymphocyte cultures, SRL and TAC diminished the number of CD30+ T cells and the sCD30 levels in the supernatant, but the effect of SRL was stronger.Conclusions
Overall, sCD30 levels are lower in SRL-treated patients, but the association between increased sCD30 levels and IF/TA at month-24 post-transplantation is stronger in SRL than in TAC-treated patients. 相似文献17.
18.
Polyxeni T. Mantani Jenifer Vallejo Irena Ljungcrantz Jan Nilsson Harry Björkbacka Gunilla Nordin Fredrikson 《Human immunology》2018,79(9):685-692
Background
The absence of interleukin-25 (IL-25) favors the induction of Th1 and Th17 immune responses in mice. Th1 immune responses have been associated with the pathology of atherosclerosis, a lipid and inflammation driven disease of the arterial wall.Purpose of research
To evaluate the effect of IL-25 on human peripheral blood mononuclear cells (hPBMCs) in the presence and absence of oxidized low density lipoprotein (oxLDL), a key player in atherosclerosis development.Principal results
Human PBMCs were incubated with recombinant human IL-25 (rhIL-25) in the presence and absence of oxLDL and analyzed with flow cytometry while cytokine secretion was measured in cell culture supernatants. The IL-25 receptor, IL-17RB, was mostly expressed on T cells. Incubation of hPBMCs with IL-25 reduced the frequency of Th17 cells. Furthermore, IL-25 inhibited the release of the Th17-inducing cytokine IL-6 from dendritic cells isolated from hPBMCs indicating that the IL-25 mediated Th17 suppression may be indirect. Moreover, IL-25 reduced the secretion of the proinflammatory cytokine IFNγ from hPBMCs. OxLDL decreased IFNγ release from hPBMCs regardless of the presence or absence of IL-25.Conclusions
IL-25 reduces Th1 and Th17 immune responses in hPBMCs raising the interesting possibility that IL-25 could have a protective role in human atherosclerosis. 相似文献19.
Marcela Caleffi da Costa Lima Caniatti Sueli Donizete Borelli Ana Lúcia Falavigna Guilherme Luiza Tamie Tsuneto 《Human immunology》2017,78(2):88-94
Background
Type I hypersensitivity, also known as IgE-mediated allergy, is a complex, multifactorial condition whose onset and severity are influenced by both genetic and environmental factors. Mite allergens stimulate the production of humoral response (IgE), especially in children, which is closely involved in atopic asthma and rhinitis.Objective
This study aimed to investigate the association between HLA class I (-A, -B, and -C), and HLA class II (-DRB1) genes in individuals sensitive to dust mites (Dermatophagoides farinae, Dermatophagoides pteronyssinus, or Blomia tropicalis) and mite-insensitive controls.Methods
396 participants were grouped as mite-sensitive and mite-insensitive according to immediate hypersensitivity as determined by skin-prick tests, and to HLA genotyping by polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO).Results
After chi-square heterogeneity testing no significant differences were observed in HLA-A, B, and C genes, except for the HLA-DRB1 locus, which, showed a negative association for DRB1104, between mite-sensitive and mite-insensitive individuals. In high resolution, DRB1104:11 allele was significantly different from all other results (P = 0.0042, OR = 0.26, and 95%CI = 0.09–0.70). The analysis stratified by etiologic agent confirmed these associations.Conclusion
Our results suggest a possible association between HLA-DRB1 genes and hypersensitivity to dust mites. 相似文献20.
Sujith Subesinghe Sander van Leuven Leena Yalakki Shirish Sangle David DCruz 《Autoimmunity reviews》2018,17(1):73-77