Relationships between UBE3A and SNORD116 expression and features of autism in chromosome 15 imprinting disorders

Abstract Chromosome 15 (C15) imprinting disorders including Prader–Willi (PWS), Angelman (AS) and chromosome 15 duplication (Dup15q) syndromes are severe neurodevelopmental disorders caused by abnormal expression of genes from the 15q11–q13 region, associated with abnormal DNA methylation and/or copy number changes. This study compared changes in mRNA levels of UBE3A and SNORD116 located within the 15q11–q13 region between these disorders and their subtypes and related these to the clinical phenotypes. The study cohort included 58 participants affected with a C15 imprinting disorder (PWS = 27, AS = 21, Dup15q = 10) and 20 typically developing controls. Semi-quantitative analysis of mRNA from peripheral blood mononuclear cells (PBMCs) was performed using reverse transcription droplet digital polymerase chain reaction (PCR) for UBE3A and SNORD116 normalised to a panel of internal control genes determined using the geNorm approach. Participants completed an intellectual/developmental functioning assessment and the Autism Diagnostic Observation Schedule-2nd Edition. The Dup15q group was the only condition with significantly increased UBE3A mRNA levels when compared to the control group (p < 0.001). Both the AS and Dup15q groups also had significantly elevated SNORD116 mRNA levels compared to controls (AS: p < 0.0001; Dup15q: p = 0.002). Both UBE3A and SNORD116 mRNA levels were positively correlated with all developmental functioning scores in the deletion AS group (p < 0.001), and autism features (p < 0.001) in the non-deletion PWS group. The findings suggest presence of novel interactions between expression of UBE3A and SNORD116 in PBMCs and brain specific processes underlying motor and language impairments and autism features in these disorders.

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Tonsils of the Soft Palate Do Not Mediate the Response of Pigs to Oral Vaccination with Heat-Inactivated Mycobacterium bovis

Clinical and Vaccine Immunology ◽

10.1128/cvi.00221-14 ◽

2014 ◽

Vol 21 (8) ◽

pp. 1128-1136 ◽

Cited By ~ 8

Author(s):

Beatriz Beltrán-Beck ◽

Beatriz Romero ◽

Mariana Boadella ◽

Carmen Casal ◽

Javier Bezos ◽

...

Keyword(s):

Wild Boar ◽

Mycobacterium Bovis ◽

Mononuclear Cells ◽

Mammalian Species ◽

Serum Antibody ◽

Control Group ◽

Mrna Levels ◽

Oral Vaccination ◽

Peripheral Blood Mononuclear ◽

Content Type

ABSTRACTMycobacterium boviscauses animal tuberculosis (TB) in cattle, humans, and other mammalian species, including pigs. The goal of this study was to experimentally assess the responses of pigs with and without a history of tonsillectomy to oral vaccination with heat-inactivatedM. bovisand challenge with a virulentM. bovisfield strain, to compare pig and wild boar responses using the same vaccination model as previously used in the Eurasian wild boar (Sus scrofa), to evaluate the use of several enzyme-linked immunosorbent assays (ELISAs) and lateral flow tests forin vivoTB diagnosis in pigs, and to verify if these tests are influenced by oral vaccination with inactivatedM. bovis. At necropsy, the lesion and culture scores were 20% to 43% higher in the controls than those in the vaccinated pigs. MassiveM. bovisgrowth from thoracic tissue samples was observed in 4 out of 9 controls but in none of the 10 vaccinated pigs. No effect of the presence or absence of tonsils was observed on these scores, suggesting that tonsils are not involved in the protective response to this vaccine in pigs. The serum antibody levels increased significantly only after challenge. At necropsy, the estimated sensitivities of the ELISAs and dual path platform (DPP) assays ranged from 89% to 94%. In the oral mucosa, no differences in gene expression were observed in the control group between the pigs with and without tonsils. In the vaccinated group, the mRNA levels for chemokine (C-C motif) receptor 7 (CCR7), interferon beta (IFN-β), and methylmalonyl coenzyme A mutase (MUT) were higher in pigs with tonsils. Complement component 3 mRNA levels in peripheral blood mononuclear cells (PBMC) increased with vaccination and decreased afterM. bovischallenge. This information is relevant for pig production in regions that are endemic forM. bovisand for TB vaccine research.

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Celiac Disease Causes Epithelial Disruption and Regulatory T Cell Recruitment in the Oral Mucosa

Frontiers in Immunology ◽

10.3389/fimmu.2021.623805 ◽

2021 ◽

Vol 12 ◽

Author(s):

Javier Sanchez-Solares ◽

Luis Sanchez ◽

Carmela Pablo-Torres ◽

Celso Diaz-Fernandez ◽

Poul Sørensen ◽

...

Keyword(s):

Celiac Disease ◽

Oral Mucosa ◽

Mononuclear Cells ◽

De Novo ◽

Current Treatment ◽

Oral Immunotherapy ◽

Control Group ◽

Mrna Levels ◽

Peripheral Blood Mononuclear ◽

Diagnostic Potential

Celiac disease (CD) is a chronic autoimmune disease characterized by an immune-triggered enteropathy upon gluten intake. The only current treatment available is lifelong Gluten Free Diet (GFD). Several extraintestinal manifestations have been described in CD, some affecting the oral mucosa. Thus, we hypothesized that oral mucosa could potentially be a target for novel biomarkers and an administration route for CD treatment. Six de novo diagnosed and seven CD patients under GFD for at least 1 year were recruited. Non-celiac subjects (n = 8) were recruited as control group. Two biopsies of the cheek lining were taken from each subject for mRNA analysis and immunohistochemical characterization. We observed a significant decrease in the expression of epithelial junction proteins in all CD patients, indicating that oral mucosa barrier integrity is compromised. FoxP3+ population was greatly increased in CD patients, suggesting that Tregs are recruited to the damaged mucosa, even after avoidance of gluten. Amphiregulin mRNA levels from Peripheral Blood Mononuclear Cells (PBMCs) and epithelial damage in the oral mucosa correlated with Treg infiltration in all the experimental groups, suggesting that recruited Tregs might display a “repair” phenotype. Based on these results, we propose that oral mucosa is altered in CD and, as such, might have diagnostic potential. Furthermore, due to its tolerogenic nature, it could be an important target for oral immunotherapy.

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Integrating the lncRNA and mRNA expression profiles of TLR4-primed mesenchymal stem cells in ankylosing spondylitis

10.21203/rs.3.rs-45893/v1 ◽

2020 ◽

Author(s):

Yuxi Li ◽

Ming Li ◽

Jiajun Huang ◽

Yuwei Liang ◽

Junshen Huang ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Mrna Expression ◽

High Throughput Sequencing ◽

Mononuclear Cells ◽

Expression Profiles ◽

Functional Networks ◽

Control Group ◽

Mrna Levels ◽

Peripheral Blood Mononuclear ◽

Qrt Pcr

Abstract Background Our previous study found that the toll-like receptor 4 (TLR4) expression of ankylosing spondylitis (AS) patients was significantly different from that of healthy donors. The goals of this study were to explore the expression profiles and functional networks of lncRNAs and mRNAs in TLR4-primed mesenchymal stromal cells from AS patients (AS-MSCs) and to clarify the mechanisms by which TLR4-primed MSCs exert immunoregulatory effects in AS. Methods Firstly, the immunoregulatory effects of MSCs were determined after TLR4 activation. Then, the differentially expressed (DE) lncRNAs and mRNAs between the control group (AS-MSCs without stimulation) and experimental group (AS-MSCs stimulated with lipopolysaccharide) were identified through high-throughput sequencing followed by qRT-PCR confirmation. Finally, bioinformatic analyses were performed to identify the critical biological functions, signalling pathways and associated functional networks involved in the TLR4-primed immunoregulatory function of AS-MSCs. Results TLR4-primed AS-MSCs showed a strong ability to inhibit the proliferation of peripheral blood mononuclear cells (PBMCs) with 1 µg/ml LPS stimulation for 4 hours. A total of 147 DE lncRNAs and 698 DE mRNAs were identified between TLR4-primed AS-MSCs and unstimulated AS-MSCs. Significant fold changes in lncRNA and mRNA levels were confirmed by qRT-PCR. GO and KEGG analysis demonstrated that the DE mRNAs and lncRNAs were highly associated with the inflammatory response. Cis-regulation prediction revealed 9 novel lncRNAs while trans-regulation prediction revealed 15 lncRNAs, respectively. Conclusions Our research describes the lncRNA and mRNA expression profiles and functional networks in TLR4-primed AS-MSCs, which is supposed to enhance the understanding of the pathogenesis of AS-MSC immunoregulatory dysfunction.

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Tumour necrosis factor-related apoptosis-inducing ligand expression in patients with diabetic nephropathy

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/1470320318785744 ◽

2018 ◽

Vol 19 (3) ◽

pp. 147032031878574 ◽

Cited By ~ 2

Author(s):

Wei-wei Chang ◽

Wei Liang ◽

Xin-ming Yao ◽

Liu Zhang ◽

Li-jun Zhu ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Mononuclear Cells ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Mrna Levels ◽

Peripheral Blood Mononuclear ◽

Necrosis Factor

Objective: The objective of this study was to evaluate the expression profile of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in patients with diabetic nephropathy (DN). Methods: A total of 126 Chinese subjects were enrolled in this study, including 42 patients with diabetes mellitus (DM), 42 patients with DN and 42 healthy controls. Real-time polymerase chain reaction was performed to analyze levels of TRAIL mRNA in peripheral blood mononuclear cells (PBMCs). Serum levels of soluble TRAIL (sTRAIL) and various cytokines were detected with a commercially available enzyme-linked immunosorbent assay kit. Results: Compared with the control group, the levels of TRAIL mRNA in PBMCs and sTRAIL in sera were both significantly decreased in the DM and DN patients ( P < 0.05). Conversely, levels of interleukin (IL)-1, IL-6, tumour necrosis factor-α and monocyte chemotactic protein-1 were higher in the DN group than in the control group. Serum levels of TRAIL positively correlated with TRAIL mRNA levels in all of the subjects examined ( P < 0.05). Conclusions: These results provide support and a theoretical basis for further research of TRAIL in regard to the pathogenesis of DN.

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Downregulation of AdipoR1 is Associated with Increased Circulating Adiponectin Levels in Serbian Chronic Kidney Disease Patients

Journal of Medical Biochemistry ◽

10.1515/jomb-2016-0007 ◽

2016 ◽

Vol 35 (4) ◽

pp. 436-442 ◽

Cited By ~ 3

Author(s):

Miron Sopić ◽

Jelena Joksić ◽

Vesna Spasojević-Kalimanovska ◽

Nataša Bogavac-Stanojević ◽

Sanja Simić-Ogrizović ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Healthy Subjects ◽

Mononuclear Cells ◽

Density Lipoprotein ◽

Control Group ◽

Mrna Levels ◽

Peripheral Blood Mononuclear ◽

Altered Expression ◽

Plasma Adiponectin

SummaryBackground:Since the rise in plasma adiponectin levels in chronic kidney disease (CKD) patients has not yet been elucidated, we sought to investigate if patients on hemodialysis (HD) have altered expression of adiponectin receptors in peripheral blood mononuclear cells (PBMCs) compared to healthy subjects.Methods:This study included 31 patients with chronic kidney disease on HD and 33 healthy subjects (CG). Circulating adiponectin levels were measured by ELISA while AdipoR1 and AdipoR2 mRNA levels in PBMCs were determined by real-time PCR.Results:Plasma adiponectin levels were significantly higher in patients compared to control group (P=0.036). After adjustment for age, BMI and creatinine, this difference became even more significant (P=0.004). In both groups adiponectin correlated with creatinine (CG: r=−0.472, P=0.006; HD: r=−0.375, P=0.038), triglycerides (CG: r=−0.490, P=0.004; HD: r=−0.488, P=0.005), insulin (CG: r=−0.386, P=0.038; HD: r=−0.506, P=0.012) and high density lipoprotein cholesterol (HDL-C) (CG: r=−0.672, P<0.001; HD: r=−0.584, P=0.001). Significantly lower expression of PBMCs AdipoR1 mRNA was found in patients compared to CG (P=0.034), while AdipoR2 mRNA levels were similarly expressed in PBMCs in both groups.Conclusions:Complex pathological processes in CKD cause downregulation of AdipoR1 which could ultimately influence AdipoR1 protein levels leading to a state of »adiponectin resistance«.

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Changes of IL-4 and IFN-g expression in monocytes and T-helper lymphocytes while modeling of systemic juvenile idiopathic arthritis in Wistar rats

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2018.02.61-69 ◽

2018 ◽

pp. 61-69

Author(s):

В.Н. Сахаров ◽

П.Ф. Литвицкий ◽

Е.И. Алексеева ◽

Н.А. Маянский ◽

Р.Ш. Закиров

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Peripheral Blood Mononuclear Cells ◽

Wistar Rats ◽

Mononuclear Cells ◽

Systemic Juvenile Idiopathic Arthritis ◽

Control Group ◽

Peripheral Blood Mononuclear ◽

Treatment Groups ◽

Blood Mononuclear Cells ◽

T Helpers

Цель исследования - изучение перепрограммирования мононуклеарных лейкоцитов на модели системного ювенильного идиопатического артрита (сЮИА), воспроизводимой у крыс Wistar с использованием полного адъюванта Фрейнда и липополисахарида. Методика. сЮИА воспроизведен у 6-месячных крыс-самцов Wistar. На 40-е сут. эксперимента животные были разделены на 3 группы: 1-я группа - контроль; 2-я - группа доксициклина; 3-я - группа дексаметазона. Взятие проб крови у животных проводили на нулевые, 41-е и 55-е сут. Мононуклеарные клетки периферической крови выделяли гравиметрически, после чего окрашивали их на маркеры и внутриклеточные цитокины. Дифференцировали моноциты (CD3-CD4+) и Т-хелперы (CD3+CD4+). Анализировали динамику внутриклеточной экспрессии интерлейкина IL-4 (рассматривали как маркер про-М2 фенотипа, так как в случае выделения из клетки ИЛ-4 служит стимулятором М2 поляризации макрофагов) и IFN-g (как маркер про-М1 фенотипа) по данным проточной цитофлуориметрии. Применяли непараметрический статистический тест Mann-Whitney-Wilcoxon в программе R для статистической обработки данных. Результаты и заключение. При моделировании сЮИА выявлено закономерное изменение фенотипа моноцитов. Применение же доксициклина и дексаметазона приводило к более ранней поляризации их по про-М2-пути в отношении моноцитов (на 41-е сут.) в сравнении с контролем. Про-М1 эффект (на 55-е сут., в сравнении с контролем) выявлен также в группах доксициклина и дексаметазона. У животных разных групп обнаружены характерные динамические изменения внутриклеточной экспрессии цитокинов. Важно, что различная направленность поляризации фенотипа при сЮИА и применении препаратов наблюдается не только у моноцитов, но и у Т-хелперов. The study objective was to evaluate targeted reprogramming of peripheral blood mononuclear cells in systemic juvenile idiopathic arthritis (sJIA) modeled in 6-month-old male Wistar rats by co-administration of complete Freund’s adjuvant and lipopolysaccharide. Methods. On day 40 of the experiment, rats were divided into three groups: control, doxycycline, and dexamethasone groups. Blood samples were collected on days 0, 41, and 55. Peripheral blood mononuclear cells were isolated gravimetrically and stained for markers and cytokines. Monocytes (CD3-CD4+) and T-helpers (CD3+CD4+) were differentiated as target cells. IL-4 was considered a marker for the pro-M2 phenotype since IL-4 can activate M2 macrophage polarization; IFN-g was considered a marker for the pro-M1 phenotype. Time-related changes in the intracellular expression of IL-4 and IFN-g were studied using flow cytometry. Data were analyzed using nonparametric statistical tests (Mann-Whitney-Wilcoxon) in the R environment for statistical computing. Results and conclusions. Monocytes (like macrophages) underwent reprogramming during the development of modeled sJIA disease. In monocytes of doxycycline and dexamethasone treatment groups, pro-M2 effects were observed earlier (day 41) than in the control group. Pro-M1 effects were observed in monocytes of doxycycline and dexamethasone groups on day 55, as compared with the control group. Characteristic time-related changes of intracellular cytokine expression were described for different groups. Importantly, the differently directed phenotype polarization was observed in sJIA and treatment groups for both monocytes and T-helpers.

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Assessment of Key Elements in the Innate Immunity System Among Patients with HIV, HCV, and Coinfections of HIV/HCV

Current HIV Research ◽

10.2174/1570162x18999200325162533 ◽

2020 ◽

Vol 18 (3) ◽

pp. 194-200

Author(s):

Maryam Moradi ◽

Alireza Tabibzadeh ◽

Davod Javanmard ◽

Saied Ghorbani ◽

Farah Bokharaei-Salim ◽

...

Keyword(s):

Innate Immunity ◽

Mononuclear Cells ◽

Hiv Infections ◽

Control Group ◽

Peripheral Blood Mononuclear ◽

Hiv Coinfection ◽

Tnf Α ◽

Immunity Genes ◽

Healthy Control ◽

Hcv Coinfection

Background: Coinfection of Hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has a higher risk of mortality than HCV or HIV monoinfection. HCV and HIV infections are specified by systemic inflammation, but the inflammation process in HCV/HIV coinfection is much complicated and is not well characterized. Objective: The aim of this study was to analyze the expression of TLR-3, TLR-7, IL-10, IFN-1 (IFN-α, IFN-β), and TNF-α in HIV, HCV and HIV/HCV co-infected patients. Methods: Forty-five patients including HIV group (n=15), HCV group (n=15), HIV/HCV coinfection group (n=15) and healthy control group (n=15) participated. Peripheral blood mononuclear cells (PBMCs) were obtained. PBMC-RNA, HCV and HIV RNA were extracted from all subjects and cDNA was synthesized. The viral load analyzed by reverse transcription-quantitative PCR (RT-qPCR), and the expression levels of IFN-α, IFN-β, TLR-3, TLR-7, TNF, and IL-10 mRNA were quantified in PBMCs. Results: The levels of IFN-I, IL-10, and TNF-α were overexpressed in all patients’ groups (P<0.05), TLR-7 was upregulated in all groups, but this upregulation was not statistically significant (p>0.05). TLR-3 showed a decrease in all patient groups (P<0.05). The statistical analysis demonstrated that TLR-3 has a negative correlation with HIV load, whereas other genes positively correlated with HIV load. In addition, TLR-3, TNF-α, and IFN-I were negatively correlated with HCV load, whereas TLR-7 and IL-10 s were positively correlated with HCV load. Conclusion: Our results showed a significant relationship between the expression level of innate immunity genes and inflammation in HCV, HIV, and HIV/HCV coinfected patients.

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Autologous Peripheral Blood Mononuclear Cells for Limb Salvage in Diabetic Foot Patients with No-Option Critical Limb Ischemia

Journal of Clinical Medicine ◽

10.3390/jcm10102213 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2213

Author(s):

Alessia Scatena ◽

Pasquale Petruzzi ◽

Filippo Maioli ◽

Francesca Lucaroni ◽

Cristina Ambrosone ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Critical Limb Ischemia ◽

Diabetic Foot ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Limb Ischemia ◽

Control Group ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

Peripheral blood mononuclear cells (PBMNCs) are reported to prevent major amputation and healing in no-option critical limb ischemia (NO-CLI). The aim of this study is to evaluate PBMNC treatment in comparison to standard treatment in NO-CLI patients with diabetic foot ulcers (DFUs). The study included 76 NO-CLI patients admitted to our centers because of CLI with DFUs. All patients were treated with the same standard care (control group), but 38 patients were also treated with autologous PBMNC implants. Major amputations, overall mortality, and number of healed patients were evaluated as the primary endpoint. Only 4 out 38 amputations (10.5%) were observed in the PBMNC group, while 15 out of 38 amputations (39.5%) were recorded in the control group (p = 0.0037). The Kaplan–Meier curves and the log-rank test results showed a significantly lower amputation rate in the PBMNCs group vs. the control group (p = 0.000). At two years follow-up, nearly 80% of the PBMNCs group was still alive vs. only 20% of the control group (p = 0.000). In the PBMNC group, 33 patients healed (86.6%) while only one patient healed in the control group (p = 0.000). PBMNCs showed a positive clinical outcome at two years follow-up in patients with DFUs and NO-CLI, significantly reducing the amputation rate and improving survival and wound healing. According to our study results, intramuscular and peri-lesional injection of autologous PBMNCs could prevent amputations in NO-CLI diabetic patients.

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Blood functional assay for rapid clinical interpretation of germline TP53 variants

Journal of Medical Genetics ◽

10.1136/jmedgenet-2020-107059 ◽

2020 ◽

pp. jmedgenet-2020-107059 ◽

Cited By ~ 1

Author(s):

Sabine Raad ◽

Marion Rolain ◽

Sophie Coutant ◽

Céline Derambure ◽

Raphael Lanos ◽

...

Keyword(s):

Mononuclear Cells ◽

Transcriptional Response ◽

Functional Assay ◽

Mrna Levels ◽

Peripheral Blood Mononuclear ◽

Patients With Cancer ◽

Pathogenic Variants ◽

Functional Variants ◽

Multiplex Ligation Probe Amplification ◽

P53 Mrna

BackgroundThe interpretation of germline TP53 variants is critical to ensure appropriate medical management of patients with cancer and follow-up of variant carriers. This interpretation remains complex and is becoming a growing challenge considering the exponential increase in TP53 tests. We developed a functional assay directly performed on patients’ blood.MethodsPeripheral blood mononuclear cells were cultured, activated, exposed to doxorubicin and the p53-mediated transcriptional response was quantified using reverse transcription–multiplex ligation probe amplification and RT-QMPSF assays, including 10 p53 targets selected from transcriptome analysis, and two amplicons to measure p53 mRNA levels. We applied this blood functional assay to 77 patients addressed for TP53 analysis.ResultsIn 51 wild-type TP53 individuals, the mean p53 functionality score was 12.7 (range 7.5–22.8). Among eight individuals harbouring likely pathogenic or pathogenic variants, the scores were reduced (mean 4.8, range 3.1–7.1), and p53 mRNA levels were reduced in patients harbouring truncating variants. We tested 14 rare unclassified variants (p.(Pro72His), p.(Gly105Asp), p.(Arg110His), p.(Phe134Leu), p.(Arg158Cys), p.(Pro191Arg), p.(Pro278Arg), p.(Arg283Cys), p.(Leu348Ser), p.(Asp352Tyr), p.(Gly108_Phe109delinsVal), p.(Asn131del), p.(Leu265del), c.-117G>T) and 12 yielded functionally abnormal scores. Remarkably, the assay revealed that the c.*1175A>C polymorphic variant within TP53 poly-adenylation site can impact p53 function with the same magnitude as a null variant, when present on both alleles, and may act as a modifying factor in pathogenic variant carriers.ConclusionThis blood p53 assay should therefore be a useful tool for the rapid clinical classification of germline TP53 variants and detection of non-coding functional variants.

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Cellular Bioenergetic and Metabolic Changes in Patients with Autism Spectrum Disorder

Current Topics in Medicinal Chemistry ◽

10.2174/1568026621666210521142131 ◽

2021 ◽

Vol 21 ◽

Author(s):

Maria Gevezova ◽

Danail Minchev ◽

Iliana Pacheva ◽

Yordan Sbirkov ◽

Ralitsa Yordanova ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Mononuclear Cells ◽

Cell Metabolism ◽

Strong Dependence ◽

Autism Spectrum ◽

Metabolic Changes ◽

Spectrum Disorder ◽

Control Group ◽

Peripheral Blood Mononuclear ◽

And Gender

Background: Although Autism Spectrum Disorder (ASD) is considered a heterogeneous neurological disease in childhood, a growing body of evidence associates it with mitochondrial dysfunction explaining the observed comorbidities. Introduction: The aim of this study is to identify variations in cellular bioenergetics and metabolism dependent on mitochondrial function in ASD patients and healthy controls using peripheral blood mononuclear cells (PBMCs). We hypothesized that PBMCs may reveal the cellular pathology and provide evidence of bioenergetic and metabolic changes accompanying the disease. Method: PBMC from children with ASD and a control group of the same age and gender were isolated. All patients underwent an in-depth clinical evaluation. A well-characterized cohort of Bulgarian children was selected. Bioenergetic and metabolic studies of isolated PBMCs were performed with a Seahorse XFp analyzer. Result: Our data show that PBMCs from patients with ASD have increased respiratory reserve capacity (by 27.5%), increased maximal respiration (by 67%) and altered adaptive response to oxidative stress induced by DMNQ. In addition, we demonstrate а strong dependence on fatty acids and impaired ability to reprogram cell metabolism. The listed characteristics are not observed in the control group. These results can contribute to a better understanding of the underlying causes of ASD, which is crucial for selecting a successful treatment. Conclusion: The current study, for the first time, provides a functional analysis of cell bioenergetics and metabolic changes in a group of Bulgarian patients with ASD. It reveals physiological abnormalities that do not allow mitochondria to adapt and meet the increased energetic requirements of the cell. The link between mitochondria and ASD is not yet fully understood, but this may lead to the discovery of new approaches for nutrition and therapy.

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