scholarly journals Protective effects of HLA-DRB1*04 subtypes in Parkinson's and Alzheimer's diseases implicate acetylated Tau PHF6 sequences

2021 ◽  
Author(s):  
Yann Le Guen ◽  
Guo Luo ◽  
Aditya Ambati ◽  
Vincent Damotte ◽  
Iris Jansen ◽  
...  
Keyword(s):  
Adaptive Immune Response ◽  
Human Leukocyte ◽  
Postmortem Brain ◽  
Neuritic Plaque ◽  
Protective Effects ◽  
Hla Association ◽  
Leukocyte Antigen ◽  
Genome Wide ◽  
Association Data ◽  
Lateral Sclerosis

Using genome-wide association data, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's (PD) or Alzheimer's (AD) disease versus controls across ancestry groups. A shared genetic association was observed across diseases at rs601945 (PD: odds ratio (OR)=0.84; 95% confidence interval, [0.80; 0.88]; p=2.2x10-13; AD: OR=0.91[0.89; 0.93]; p=1.8x10-22), and with a protective HLA association recently reported in amyotrophic lateral sclerosis (ALS). Hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03, and absent for HLA-DRB1*04:05. The same signal was associated with decreased neurofibrillary tangles (but not neuritic plaque density) in postmortem brain and was more strongly associated with Tau levels than Aβ42 levels in the cerebrospinal fluid. Finally, protective HLA-DRB1*04 subtypes strongly bound aggregation-prone Tau PHF6 sequence, but only when acetylated at K311, a modification central to aggregation. A HLA-DRB1*04-mediated adaptive immune response, potentially against Tau, decreases PD, AD and ALS risk, offering the possibility of new therapeutic avenues.

scholarly journals Hypothetical COVID-19 protection mechanism: hints from centenarians

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Franca Rosa Guerini ◽  
Matteo Cesari ◽  
Beatrice Arosio
Keyword(s):  
Adaptive Immune Response ◽  
Human Leukocyte ◽  
Human Longevity ◽  
Biological Mechanisms ◽  
Protection Mechanism ◽  
Leukocyte Antigen ◽  
Adaptive Immune ◽  
Life Threatening ◽  
Coronavirus Infection ◽  
Rule Out

AbstractThe risk of serious complications and the fatality rate due to COVID-19 pandemic have proven particularly higher in older persons, putting a further strain in healthcare system as we dramatically observed.COVID-19 is not exclusively gerophile (géro “old” and philia “love”) as young people can be infected, even if older people experience more severe symptoms and mortality due to their greater frailty. Indeed, frailty could complicate the course of COVID-19, much more than the number of years lived. As demonstration, there are centenarians showing remarkable capacity to recover after coronavirus infection.We hypothesize that centenarian’s portfolio could help in identifying protective biological mechanisms underlying the coronavirus infection.The human leukocyte antigen (HLA) is one of the major genetic regions associated with human longevity, due to its central role in the development of adaptive immune response and modulation of the individual’s response to life threatening diseases. The HLA locus seems to be crucial in influencing susceptibility and severity of COVID-19.In this hypothesis, we assume that the biological process in which HLA are involved may explain some aspects of coronavirus infection in centenarians, although we cannot rule out other biological mechanisms that these extraordinary persons are able to adopt to cope with the infection.

scholarly journals Neolithic genomes reveal a distinct ancient HLA allele pool and population transformation in Europe

2019 ◽  
Author(s):  
Alexander Immel ◽  
Christoph Rinne ◽  
John Meadows ◽  
Rodrigo Barquera ◽  
András Szolek ◽  
...  
Keyword(s):  
Western Europe ◽  
Viral Infections ◽  
Human Leukocyte ◽  
Neolithic Period ◽  
Late Neolithic ◽  
Leukocyte Antigen ◽  
Cultural Transformations ◽  
Farming Community ◽  
Genome Wide ◽  
A Genome

AbstractThe Wartberg culture (WBC, 3,500-2,800 BCE) dates to the Late Neolithic period, a time of important demographic and cultural transformations in western Europe. We perform a genome-wide analysis of 42 individuals who were interred in a WBC collective burial in Niedertiefenbach, Germany (3,300-3,200 cal. BCE). Our results highlight that the Niedertiefenbach population indeed emerged at the beginning of the WBC. This farming community was genetically heterogeneous and carried a surprisingly large hunter-gatherer ancestry component (40%). We detect considerable differences in the human leukocyte antigen gene pool between contemporary Europeans and the Niedertiefenbach individuals whose immune response was primarily geared towards defending viral infections.

Multiple sclerosis and amyotrophic lateral sclerosis: a human leukocyte antigen challenge

2017 ◽  
Vol 38 (8) ◽  
pp. 1501-1503 ◽  
Author(s):  
Vincenzo Dattola ◽  
Fausto Famà ◽  
Margherita Russo ◽  
Rocco Salvatore Calabrò ◽  
Anna Lisa Logiudice ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Amyotrophic Lateral Sclerosis ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Antigen Challenge ◽  
Leukocyte Antigen ◽  
Lateral Sclerosis

scholarly journals HLA and sleep parameter associations in post-H1N1 narcolepsy type 1 patients and first-degree relatives

SLEEP ◽  
2019 ◽  
Vol 43 (3) ◽  
Author(s):  
Hilde T Juvodden ◽  
Marte K Viken ◽  
Sebjørg E H Nordstrand ◽  
Rannveig Viste ◽  
Lars T Westlye ◽  
...  
Keyword(s):  
Human Leukocyte ◽  
Sleep Paralysis ◽  
Protective Effects ◽  
Hla Alleles ◽  
Leukocyte Antigen ◽  
First Degree Relatives ◽  
Sleep Parameters ◽  
Similar Disease ◽  
Hypnagogic Hallucinations

Abstract Study Objectives To explore HLA (human leukocyte antigen) in post-H1N1 narcolepsy type 1 patients (NT1), first-degree relatives and healthy controls, and assess HLA associations with clinical and sleep parameters in patients and first-degree relatives. Methods Ninety post-H1N1 NT1 patients and 202 of their first-degree relatives were HLA-genotyped (next generation sequencing) and phenotyped (semistructured interviews, Stanford Sleep Questionnaire, polysomnography, and multiple sleep latency test). HLA allele distributions were compared between DQB1*06:02-heterozygous individuals (77 patients, 59 parents, 1230 controls). A subsample (74 patients, 114 relatives) was investigated for associations between HLA-loci and continuous sleep variables using logistic regression. Identified candidate HLA-loci were explored for HLA allele associations with hypnagogic hallucinations and sleep paralysis in 90 patients, and patient allele findings were checked for similar associations in 202 relatives. Results DQB1*06:02 heterozygous post-H1N1 NT1 patients (84.4% H1N1-vaccinated) showed several significant HLA associations similar to those reported previously in samples of mainly sporadic NT1, i.e. DQB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:07, DRB1*11:04, A*25:01, B*35:03, and B*51:01, and novel associations, i.e. B*14:02, C*01:02, and C*07:01. Parents HLA alleles did not deviate significantly from controls. The HLA-C locus was associated with sleep parameters in patients and relatives. In patients C*02:02 seems to be associated with protective effects against sleep paralysis and hypnagogic hallucinations. Conclusions Our findings of similar risk/protective HLA-alleles in post-H1N1 as in previous studies of mainly sporadic narcolepsy support similar disease mechanisms. We also report novel allelic associations. Associations between HLA-C and sleep parameters were seen independent of NT1 diagnosis, supporting involvement of HLA-C in sleep subphenotypes.

scholarly journals Clinical Study on the Melarsoprol-Related Encephalopathic Syndrome: Risk Factors and HLA Association

2020 ◽  
Vol 5 (1) ◽  
pp. 5
Author(s):  
Jorge Seixas ◽  
Jorge Atouguia ◽  
Teófilo Josenando ◽  
Gedeão Vatunga ◽  
Constantin Miaka Mia Bilenge ◽  
...  
Keyword(s):  
Risk Factors ◽  
Late Stage ◽  
Democratic Republic Of Congo ◽  
Human Leukocyte ◽  
P Value ◽  
Hla Association ◽  
Leukocyte Antigen ◽  
Hla Dr ◽  
Genetically Determined ◽  
Control Study

Melarsoprol administration for the treatment of late-stage human African trypanosomiasis (HAT) is associated with the development of an unpredictable and badly characterized encephalopathic syndrome (ES), probably of immune origin, that kills approximately 50% of those affected. We investigated the characteristics and clinical risk factors for ES, as well as the association between the Human Leukocyte Antigen (HLA) complex and the risk for ES in a case-control study. Late-stage Gambiense HAT patients treated with melarsoprol and developing ES (69 cases) were compared to patients not suffering from the syndrome (207 controls). Patients were enrolled in six HAT treatment centres in Angola and in the Democratic Republic of Congo. Standardized clinical data was obtained from all participants before melarsoprol was initiated. Class I (HLA-A, HLA-B, HLA-Cw) and II (HLA-DR) alleles were determined by PCR-SSOP methods in 62 ES cases and 189 controls. The principal ES pattern consisted in convulsions followed by a coma, whereas ES with exclusively mental changes was not observed. Oedema, bone pain, apathy, and a depressed humour were associated with a higher risk of ES, while abdominal pain, coma, respiratory distress, and a Babinski sign were associated with higher ES-associated mortality. Haplotype C*14/B*15 was associated with an elevated risk for ES (OR: 6.64; p-value: 0.008). Haplotypes A*23/C*14, A*23/B*15 and DR*07/B*58 also showed a weaker association with ES. This result supports the hypothesis that a genetically determined peculiar type of immune response confers susceptibility for ES.

scholarly journals HLA Polymorphisms and Risk of Glioblastoma in Koreans

2021 ◽  
Author(s):  
Stephen Ahn ◽  
Haeyoun Choi ◽  
In-Cheol Baek ◽  
Soon A. Park ◽  
Yeo Song Kim ◽  
...  
Keyword(s):  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Control Group ◽  
Hla Association ◽  
Hla Polymorphism ◽  
Leukocyte Antigen ◽  
Cancer Types ◽  
Control Study

Purpose Immune responses for cancer cells can be altered according to genetic variation of human leukocyte antigen (HLA). Association of HLA polymorphism with risk of various cancer types is well known. However, the association between HLA and glioblastoma (GBM) remains uncertain. We sought to evaluate the association of HLA polymorphism with risk of GBM development in Koreans. Materials and Methods A case-control study was performed to identify the odds ratios (OR) of HLA class I and II genes for GBM. The control group consisted of 142 healthy Korean volunteers, and the GBM group was 80 patients with newly diagnosed GBM at our institution. HLA class I (-A, -B, and –C) and class II (-DR, -DQ, and –DP) genotyping was performed by high-resolution polymerase chain reaction (PCR)-sequence-based typing (PCR-SBT) methods. Results There were significantly decreased frequencies of HLA-A*26:02 (OR 0.22 CI 0.05-0.98), HLA-C*08:01 (OR 0.29 CI 0.10-0.87), and HLA-DRB1*08:03 (OR 0.32 CI 0.11-0.98), while there was significantly increased frequency of HLA-C*04:01 (OR 2.29 CI 1.05-4.97). In analysis of haplotypes, the frequency of DRB1*14:05-DQB1*05:03 was significantly decreased (OR 0.22 CI 0.05-0.98). Conclusion This study suggests that genetic variations of HLA may affect GBM development in Koreans. Further investigations with larger sample sizes are needed to delineate any potential role of the HLA polymorphisms in the pathogenesis of GBM development.

scholarly journals An updated view of the pathogenesis of steroid-sensitive nephrotic syndrome

2022 ◽  
Author(s):  
Tomoko Horinouchi ◽  
Kandai Nozu ◽  
Kazumoto Iijima
Keyword(s):  
Nephrotic Syndrome ◽  
Genome Wide Association Study ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Genome Wide ◽  
A Genome ◽  
Immunological Mechanisms ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive ◽  
Genetic Techniques

Abstract Idiopathic nephrotic syndrome is the most common childhood glomerular disease. Most forms of this syndrome respond to corticosteroids at standard doses and are, therefore, defined as steroid-sensitive nephrotic syndrome (SSNS). Immunological mechanisms and subsequent podocyte disorders play a pivotal role in SSNS and have been studied for years; however, the precise pathogenesis remains unclear. With recent advances in genetic techniques, an exhaustive hypothesis-free approach called a genome-wide association study (GWAS) has been conducted in various populations. GWASs in pediatric SSNS peaked in the human leukocyte antigen class II region in various populations. Additionally, an association of immune-related CALHM6/FAM26F, PARM1, BTNL2, and TNFSF15 genes, as well as NPHS1, which encodes nephrin expressed in podocytes, has been identified as a locus that achieves genome-wide significance in pediatric SSNS. However, the specific mechanism of SSNS development requires elucidation. This review describes an updated view of SSNS pathogenesis from immunological and genetic aspects, including interactions with infections or allergies, production of circulating factors, and an autoantibody hypothesis.

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