Expression of HLA-DR, CD80, and CD86 in Healthy Aging and Alzheimer’s Disease

Busse, Stefan; Steiner, Johann; Alter, Juliane; Dobrowolny, Henrik; Mawrin, Christian; Bogerts, Bernhard; Hartig, Roland; Busse, Mandy

doi:10.3233/jad-150217

Cited by 24 publications

(21 citation statements)

References 42 publications

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“…The HLA class II region is critical in mediating the humoral immune response [11]. Among the genes mentioned above, HLA-DQB1 and HLA-DRB1 are associated with many immunological diseases, such as pemphigus vulgaris [12], narcolepsy [13], Alzheimer’s disease [14], and dermatomyositis [15].…”

Section: Introductionmentioning

confidence: 99%

HLA-DQB1 and HLA-DRB1 Variants Confer Susceptibility to Latent Autoimmune Diabetes in Adults: Relative Predispositional Effects among Allele Groups

Zhang

Lin

Yuan

et al. 2019

Genes

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Latent autoimmune diabetes in adults (LADA) was recently demonstrated to be the most frequent form of adult-onset autoimmune diabetes mellitus. Case–control studies have investigated the relationship between human leukocyte antigen (HLA)-DQB1 and HLA-DRB1 polymorphisms and LADA risk, but their conclusions are inconsistent. This study aimed to more precisely explore the correlation between these HLA gene variants and LADA development. Eight databases, including PubMed, Embase, and Medline, were systematically searched for relevant studies up to September 15, 2018. We performed this retrospective study using meta-analysis and relative predispositional effect (RPE) methods. The meta-analysis results indicated that DQB1*02 (odds ratio (OR) = 1.685, pc < 0.005) and DQB1*06 (OR = 0.604, pc = 0.010) have opposite effects on susceptibility to LADA, while a significant decrease in LADA risk caused by DQB1*05 (OR = 0.764, pc = 0.100) disappeared upon Bonferroni correction. The RPE method confirmed the roles of DQB1*02 (χ² = 46.475, p < 0.001) and DQB1*06 (χ² = 17.883, p < 0.001) and further suggested protective effects of DQB1*05 (χ² = 16.496, p < 0.001). Additionally, the meta-analysis results showed that DRB1*03 (OR = 2.685, pc < 0.013), DRB1*04 (OR = 1.954, pc < 0.013), and DRB1*09 (OR = 1.346, pc < 0.013) are associated with increased LADA risk, while DRB1*12 (OR = 0.600, pc < 0.013) and DRB1*13 (OR = 0.583, pc < 0.013) carriers have a decreased risk of developing LADA. Furthermore, the RPE method revealed that DRB1*03 (χ² = 98.754, p < 0.001), DRB1*04 (χ² = 94.685, p < 0.001), DRB1*09 (χ² = 40.489, p < 0.001), DRB1*01 (χ² = 12.181, p < 0.001), DRB1*07 (χ² = 10.882, p = 0.001), and DRB1*08 (χ² = 5.000, p = 0.025) play protective roles against LADA. LADA showed a close relationship with genetic polymorphisms of HLA-DQB1 and WHLA-DRB1, which could contribute to a better understanding of disease pathogenesis and the identification of predisposing loci in the diagnosis and treatment of LADA.

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Section: Introductionmentioning

confidence: 99%

HLA-DQB1 and HLA-DRB1 Variants Confer Susceptibility to Latent Autoimmune Diabetes in Adults: Relative Predispositional Effects among Allele Groups

Zhang

Lin

Yuan

et al. 2019

Genes

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“…Few studies have analyzed the expression of these ligands in the elderly. A recent study showed an increase in the basal expression of CD80‐CD86 in immunocompetent individuals aged 70‐79 years compared to those aged 20‐29 years 46 . One proposed explanation for this observation is the chronic inflammation status reported in the elderly (inflamm‐aging), possibly due to dysregulation of the basal state of the transcription factor, NF‐κB 7 .…”

Section: Discussionmentioning

confidence: 99%

Longitudinal immune profile reveals reduced function of pro-inflammatory monocytes with age following kidney transplantation

Désy

Vallin

Béland

et al. 2021

American Journal of Transplantation

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Toxicity of immunosuppression, notably the risk of infection, increases with age. However, the dynamic changes in innate immune response following transplantation are unclear. Based on recent observations, we hypothesized that pro‐inflammatory capacity would decrease with age. We analyzed approximately 300 PBMC samples collected longitudinally in 45 de novo, adult kidney recipients and performed detailed phenotypic and functional profiling of monocytes and T cell subsets. Inflammatory response to TLR4 stimulation and indirect allostimulation using mismatched HLA peptides were assessed. In patients aged ≥56 years, TNF‐α production by intermediate monocytes was similar to that in younger patients early posttransplant, but diminished substantially later. Adjusted analyses suggested that this was not attributable to confounding factors. In contrast, the alloimmune response to HLA peptides measured by IFN‐γ in CD4+ T cells and TNF‐α in monocytes was stable over time, but was low in older recipients. Measurement of CD80‐86 surface expression revealed no signal for a lower costimulation capacity of APCs. These results suggest that older recipients have a reduced function of their innate pro‐inflammatory immune cells posttransplant while maintaining a stable, low alloimmune response over time. The effect of reduced immunosuppressant doses on preventing this phenomenon needs to be clarified.

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“…The DEGs obtained were remarkably enriched in GO terms and pathway under defense response, whole membrane, molecular transducer activity, neutrophil degranulation, ion transport, integral component of plasma membrane, transporter activity and neuronal system. [76], BTK (Bruton tyrosine kinase) [77], C7 [78], PLA2G7 [79], SOCS3 [80], OLR1 [81], LIPA (lipase A, lysosomal acid type) [82], CD86 [83], TLR5 [ [100], AGRN (agrin) [101] and GP6 [102] have been shown as a promising biomarkers in Alzheimer's disease. Field et al [103], Lincoln et al [104], Ziliotto et al [105], El Sharkawi et al [106], Cossins et al [107], Mirowska-Guzel et al [108], Asouri et al [109], Cardamone et al [110], Begovich et al [111], Bennetts et al [112], Iparraguirre et al [113] and Oldoni et al [114] reported that HLA-DPB1, HLA-DQA1, CCL18, CCL20, MMP7, IL1A, IL2RA, CYBB (cytochrome b-245 beta chain), PTPN22, HLA-DMB, ANXA2 and CHIT1expression were associated with progression of multiple sclerosis, but these genes might be liable for advancement of dementia.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Vastrad¹,

Vastrad²

2021

Preprint

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To provide a better understanding of dementia at the molecular level, this study aimed to identify the genes and key pathways associated with dementia by using integrated bioinformatics analysis. Based on the expression profiling by high throughput sequencing dataset GSE153960 derived from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) between patients with dementia and healthy controls were identified. With DEGs, we performed a series of functional enrichment analyses. Then, a protein protein interaction (PPI) network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network was constructed, analyzed and visualized, with which the hub genes miRNAs and TFs nodes were screened out. Finally, validation of hub genes was performed by using receiver operating characteristic curve (ROC) analysis and RT PCR. A total of 948 DEGs were screened out, among which 475 genes were up regulated; while 473 were down regulated. Functional enrichment analyses indicated that DEGs were mainly involved in defense response, ion transport, neutrophil degranulation and neuronal system. The hub genes (CDK1, TOP2A, MAD2L1, RSL24D1, CDKN1A, NOTCH3, MYB, PWP2, WNT7B and HSPA12B) were identified from PPI network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network. We identified a series of key genes along with the pathways that were most closely related with dementia initiation and progression. Our results provide a more detailed molecular mechanism for the advancement of dementia, shedding light on the potential biomarkers and therapeutic targets.

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Expression of HLA-DR, CD80, and CD86 in Healthy Aging and Alzheimer’s Disease

Cited by 24 publications

References 42 publications

HLA-DQB1 and HLA-DRB1 Variants Confer Susceptibility to Latent Autoimmune Diabetes in Adults: Relative Predispositional Effects among Allele Groups

HLA-DQB1 and HLA-DRB1 Variants Confer Susceptibility to Latent Autoimmune Diabetes in Adults: Relative Predispositional Effects among Allele Groups

Longitudinal immune profile reveals reduced function of pro-inflammatory monocytes with age following kidney transplantation

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

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