Role of autoimmunity in Neuronal damage in children with Autism spectrum disorder.

"Autism spectrum disorder (ASD) is complex neurodevelopmental disorder characterized by impairments in three core behavioral: social deficits, impaired communication, and repetitive behaviors." There is developing indication and emerging data that irregular autoimmune responses to the central nervous system may play a pathogenic role in patients with autism spectrum disorder." The aim of this review was to discuss the updated research carried out at Autism research and treatment center, King Saud University, Riyadh, Kingdom of Saudi Arabia particularly on the role of autoimmunity in Autism spectrum disorder. This review also present state of information available about the role of autoimmunity biomarkers involved in the neuronal damage of central nervous system in autistic children. The systematic literature search was carried out using Google Scholar, Science direct and PubMed databases on the role of autoimmunity in autism and reviewed all relevant articles published in peer reviewed journals by Autism research and treatment center, King Saud University, Riyadh, Kingdom of Saudi Arabia till April, 2022. We searched relevant articles using key words Autism spectrum disorder, Autoimmunity, Neuroinflamation and Central nervous system. This review revealed that plasma levels of autoimmunity related factors/ markers were altered in patients with autism. Significant change in blood markers in subjects with ASD may resulted in several years of decreased neutrotrophic support along with increasing impairment in relationship with down-regulated inflammation that may play a role in the ASD. Overall, the role of autoimmunity in ASD subjects with excess of anti-brain antibodies suggest that in some patients, autoantibodies that target the CNS may be pathological factor in neuronal growth in autistic children. Large cohort studies with well-defined and specially pheno typed autistic groups and matched healthy controls are required to examine the role of autoantibodies in the pathology of subjects with ASD.

Lifestyle habits and obesity indices among male adolescents in Riyadh, Saudi Arabia.

Obesity among adolescents is a global health apprehension which requires early prevention. The aim of this study was to determine the association between lifestyle habits including physical activity, sedentary behaviors and eating habits with obesity indices of body mass index (BMI) and waist-to-height ratio (WHtR) among male adolescents in Riyadh, Saudi Arabia. We randomly selected 471 secondary school male adolescents aged 14-18 years. A pre-validated self-reported questionnaire was used to record the data on physical activity level, sedentary behaviors, sleep duration and eating habits. The International Obesity Task Force (IOTF) cutoff values for adolescents under 18 years of age were used to define overweight and obesity. Total energy expenditure was calculated using metabolic equivalent-minutes per week. Anthropometry including weight, height, BMI, waist circumference, waist/height ratio (WHtR), were assessed. 53.7% and 48.4% of the adolescents were overweight/obese and had abdominal obesity; respectively. Those with overweight and obesity or above 50% of WHtR were much less active in terms of METs-min/week from vigorous-intensity sports, sum of all METs-min/week from all vigorous-intensity physical activity, total METs-min/week from all physical activity compared with non-obese adolescents and below 50% of WHtR. The present study identified the lifestyle habits that were associated with obesity and may represent valid targets for the prevention and management of obesity among Saudi adolescents. Knowledge of the factors that contribute to obesity could be used in preventive programs for the control of obesity among adolescents.

Impact of supervised exercise training on systemic sclerosis with multiple organ involvement: A case report.

Supervised training exercises are the mainstay of pulmonary rehabilitation (PR) in patients with chronic lung diseases like interstitial lung disease (ILD). A 40 years old female patient with systemic sclerosis clinically presenting with usual interstitial pneumonia (UIP) and pulmonary hypertension underwent an eight-week supervised exercise training programme. Forced Vital Capacity (FVC) showed improvement from 48.7% to 54% of predicted baseline, while the initial six-minute walk test (MWT) distance also showed a considerable increase of 15.4% from the baseline after completion of the exercise training. A remarkable improvement was noticed in muscle strength for both the upper and the lower limbs. There was an increase of 79.4% right side handgrip, 25% left side handgrip, and 30.9% increase in lower limbs than baseline strength. The findings show that an exercise training programme under the supervision of trained and competent staff can benefit the improvement of lung function and muscle strength in a patient suffering from chronic lung diseases.

The possible link between Fetuin-A Protein and Neuro-inflammation in Children with Autism Spectrum Disorder.

OBJECTIVES: To investigate the blood plasma levels of Fetuin-A protein in children with Autism Spectrum Disorder (ASD) and healthy controls that could offer novel diagnostic biomarkers of disease development in ASD. Another objective was to investigate the severity of autistic children by Childhood Autism Rating Scale (CARS) and Short Sensory Profile (SSP). METHODS: This case control study was carried out at Autism Research and Treatment (ART) Center, King Saud University, Riyadh, Saudi Arabia, from October 2019 to February 2020. Plasma concentration of Fetuin-A was analyzed by enzyme-linked immunosorbent assay (ELISA) in ASD subjects (n=46) and normal controls (n=44). Correlation among Fetuin-A levels, CARS and SSP was established by Spearman's correlation coefficient (r). RESULTS: Overall, autistic children had significantly (p= 0.0.02) lower Fetuin-A concentration [50.76 (22.2-68.5) ng/ml] than those of healthy controls [53.7 (35.6-99.7) ng/ml] [median (interquartile range)]. Children with mild to moderate autism (n=24, 52%) also showed significantly lower Fetuin-A levels [50.0 (30.0-68.2) ng/ml], (p =0.02} than healthy controls [53.7 (35.6-99.7) ng/ml] [median (IQR)]. However, there was no significant change (p = 0.71) observed between the Fetuin-A levels of children with severe autism [51.8 (22.2-68.5)] ng/ml, mild to moderate autism [50 (30-68.2)] ng/ml [median (IQR)] and healthy controls (p=0.12). Also no significant correlations between Fetuin-A, CARS and SSP were observed (CARS, r= 0.024, p=0.88; SSP, r= -0.003, p=0.98). CONCLUSION: Overall the low Fetuin-A plasma values in ASD subjects, most likely show that Fetuin-A could be associated in the physiology of autism. Further studies with larger patient and control cohorts will be necessary to determine whether Fetuin-A can be used as a biomarker for ASD.

Impact of supervised exercise training on pulmonary function parameters, exercise capacity and Irisin Biomarker in Interstitial lung disease patients.

OBJECTIVES: To assess the impact of supervised exercise training (SET) on pulmonary function Parameters, exercise capacity and Irisin biomarker in Interstitial Lung Disease (ILD) patients. METHODS: Ten (10)patients with ILD and 18 healthy controls of age between 30-40+ years were selected for 8-week SET program. Before and after SET all subjects performed exercise capacity six minutes' walk test (6MWT), heart rate (HR) changes were recorded, shortness of Breath Respiratory Questionnaire (SOBQ) was obtained and Irisin levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA). This interventional study was carried out at Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2018 to February 2019. RESULTS: Mean six minutes' walk distance (6MWD) was 395 ± 68.4 m at 1st visit increased significantly (p=0.001) to 458.8± 87.1 mat 15 visit. However, 6MWD values found significantly higher in controls (517.4±84.1 m; 561.7±81.6 m; p=0.013) than ILD patients. Overall change (difference between post and pre exercise) in HRvalue was recorded lower in ILD patients (30-35 bpm) as compared to controls (40-45 bpm). Moreover, ILD patients had overall higher SOBQ score than controls. Pre SET Irisin levels of ILD patients (4.24 ±1.73 pg/ml) and controls (3.43 ±1.04pg/ml) were found unchanged dafter SET (4.48±2.02pg/ml, 3.39 ±1.41pg/ml, p=0.677, p=0.093)respectively. However, patients Irisin values were found higher as compared to controls before and after SET. CONCLUSION: Exercise capacity and Dyspneain patients with ILD were improved after 8-week of SET program. No major changes in Irisin levels among patients with ILD and controls were observed. Additional research requires to be carried out on large number of subjects to deter Minutese the advantages of exercise in ILD.

Impact of environmental pollution, dietary factors and diabetes mellitus on Autism Spectrum Disorder (ASD).

Autism spectrum disorder (ASD) is complex neurodevelopmental condition described by impairments in three main behavioral areas: social deficits, impaired communication, and repetitive behaviors. Despite many years of vast study, the causes of ASD are still unknown. Various risk factors including genetic, infectious, metabolic and immunological have been investigated however, environmental, nutritional and diabetes related risk factors have not received sufficient attention. This study has provided an insight into the comprehensive interaction between environmental pollution, dietary factors and diabetes mellitus that could lead to the advancement of this debilitating neurodevelopment disorder. The literature search was done using PubMed and Google Scholar databases up to October 2018. Key words "Environmental Pollution", "Nutritional Factors", "Diabetes Mellitus", "Autism Spectrum Disorder" were selected.

Impact of Auditory Integrative Training on Transforming Growth Factor-ß1 and Its Effect on Behavioral and Social Emotions in Children with Autism Spectrum Disorder.

OBJECTIVE: To explore the impact of auditory integrative training (AIT) on the inflammatory biomarker transforming growth factor (TGF)-ß1 and to assess its effect on social behavior in children with autism spectrum disorder (ASD). SUBJECTS AND METHODS: In this cross-sectional study, 15 patients (14 males and 1 female) with ASD aged 3-12 years were recruited. All were screened for autism using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Plasma levels of TGF-ß1 were measured in all patients using a sandwich enzyme-linked immunoassay (ELISA) immediately and 1 and 3 months after the AIT sessions. Pre- and post-AIT behavioral scores were also calculated for each child using the Childhood Autism Rating Scale (CARS), the Social Responsiveness Scale (SRS), and the Short Sensory Profile (SSP). Data were analyzed using the Statistical Package for the Social Sciences (SPSS 21.0 for Windows). RESULTS: Plasma levels of TGF-ß1 significantly increased to 85% immediately after AIT (20.13 ± 12 ng/mL, p < 0.05), to 95% 1 month after AIT (21.2 ± 11 ng/mL, p < 0.01), and to 105% 3 months after AIT (22.25 ± 16 ng/mL, p < 0.01) compared to before AIT (10.85 ± 8 ng/mL). Results also revealed that behavioral rating scales (CARS, SRS, and SSP) improved in terms of disease severity after AIT. CONCLUSION: Increased plasma levels of TGF-ß1 support the therapeutic effect of AIT on TGF-ß1 followed by improvement in social awareness, social cognition, and social communication in children with ASD. Furthermore, TGF-ß1 was associated with severity in all scores tested (CARS, SRS, and SSP); if confirmed in studies with larger sample sizes, TGF-ß1 may be considered as a marker of ASD severity and to assess the efficacy of therapeutic interventions.

Secretagogin (SCGN) Plasma Levels and their Association with Cognitive and Social Behavior in Children with Autism Spectrum Disorder ASD).

OBJECTIVE: To investigate the secretagogin (SCGN) plasma levels in children with autism spectrum disorder (ASD) compared to age and gender-matched healthy control, and its association with cognitive and social behaviors by using childhood autism rating scale (CARS) and social responsiveness scale (SRS). STUDY DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2015 to May 2016. METHODOLOGY: SCGN levels were determined in the plasma of thirty-seven (37) autistic children using enzyme-linked immunosorbent assay (ELISA), categorized as mild-moderate and severe as indicated by their CARS scores and compared with thirty (30) age and gender-matched control samples. Correlation between SCGN levels and different cognitive and social behavior scales (CARS and SRS) was determined by Spearman's correlation coefficient (r). RESULTS: The results indicated that autistic children (n=37) had significantly (p= 0.005) lower plasma level of SCGN {45.7 (26.2) ng/ml [median (IQR)]} than those of healthy controls {n=30, 70.8 (48.6) ng/ml [median (IQR)]}. Children with severe (n=28, 76%) as well as mild to moderate autism (n=09, 24%) also exhibited significantly lower SCGN levels {47.5 (27) ng/ml [median (IQR)], p =0.014} and {45.7 (16.6) ng/ml [median (IQR)], p = 0.02)}, respectively than healthy controls {n=30, 70.8 (48.6) ng/ml [median (IQR)]}. However, there was no significant difference between the SCGN levels of children with mild to moderate and severe autism (p = 0.66). Spearman's correlation coefficient (r) was used to determine the relationships between SCGN levels and different variables (CARS, SRS). However, the results showed no significant correlation between SCGN and these scales. (CARS, r=-0.03, p=0.86; SRS, r=0.21, p=0.20). CONCLUSION: The low SCGN plasma levels in children with ASD probably indicate that SCGN might be implicated in the pathogenesis of autism. However, these data should be treated with caution until further investigations are performed using larger sample sizes to determine whether the decrease in plasma SCGN levels is a mere consequence of autism or it plays a pathogenic role in the disease.

Cluster of Differentiation 5 (CD5) Levels in the Plasma of Children with Autism Spectrum Disorder (ASD).

OBJECTIVE: To investigate the cluster of differentiation 5 (CD5) plasma levels and their association with childhood autism rating scale (CARS) in subjects with autism spectrum disorder (ASD) compared to age and gender matched healthy controls, and to explore the link between CD5, severity, and autoimmunity in autism. STUDY DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2014 to May 2015. METHODOLOGY: CD5 levels were determined in the plasma of thirty-one (31) patients using enzyme-linked immunosorbent assay (ELISA), categorized as mild-moderate and severe as indicated by their Childhood Autism Rating Scale (CARS) score and compared to thirty-three (33) age and gender-matched control samples. RESULTS: The preliminary data indicated that children with severe autism (n=12), exhibited significantly (p=0.02) higher plasma level of CD5 [0.55 (0.14-12) pg/ml {median (interquartile range=IQR)}] than those of normal controls [n=33, 0.29 (0.08-0.79) pg/ml {median (IQR)}] and children with mild to moderate autism [n=19, 0.26 (0.13-1.42) pg/ml, {median (IQR)}, p=0.08]. However, there was no significant difference between the CD5 levels of children with mild to moderate autism and normal controls (p = 0.62). Diagnoses of autistic children based on the CARS score >30. Disease severity and the CARS score, which represent stereotyped patterns of behavior in children with autism, were positively correlated (r = 0.43, p = 0.02). CONCLUSION: The high CD5 plasma levels in patients with severe ASD, probably indicated that CD5 might be implicated in the physiology of autism. However, this finding should be treated with caution until further investigations are performed with larger populations to determine whether the increase in plasma CD5 levels is a mere consequence of autism or it plays a pathogenic role in the disease.

Association of Learning and Memory Calcineurin Binding Protein with Autism Spectrum Disorders.

OBJECTIVE: To determine the association of learning and memory calcineurin binding (CABIN1) protein with autism spectrum disorders. STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: The Autism Research and Treatment Center, King Khalid University Hospital, Riyadh, Saudi Arabia, from October 2013 to May 2014. METHODOLOGY: Serum levels of CABIN1 protein in 62 (64%) autistic male children were analysed and 35 (36%) age healthy children measured by using ELISA. The diagnosis of autism was made, based on the criteria of autism as defined in the DSM-IV. CARS (childhood autism rating scale) was used for the assessment of autistic severity. Data was analysed on SPSS version 21. Mann-Whitney U-test was used for comparisons of CABIN1 protein levels between the autistic and control groups at a p-value of <0.05. Spearman's correlation coefficient (r) was used to determine the relationships between different variables. RESULTS: There was no significant difference between the levels of CABIN1 between the 1.12 (0.01-8.8) pg/ml and healthy (1.51, 0.12-4.32) pg/ml in children. However, children with mild to moderate autism had higher CABIN1 protein level (1.27 pg/ml, 0.01-10.240) than children with severe autism (0.80 pg/ml, 0.01-4.25, p=0.145). In addition, there was no significant relationships among the serum level of CABIN1 protein, the CARS score, and age. CONCLUSION: CABIN1 protein level for children with autism was not significantly different from controls subjects as well as between children with mild to moderate and severe autism.

Activity-Regulated Cytoskeleton-Associated Protein Dysfunction May Contribute to Memory Disorder and Earlier Detection of Autism Spectrum Disorders.

OBJECTIVE: To explore a possible role for activity-regulated cytoskeleton-associated (Arc/Arg3.1) protein in the clinical identification of children with autism. SUBJECTS AND METHODS: The plasma levels of Arc/Arg3.1 in 62 boys with autism and 32 healthy boys were measured using an enzyme-linked immunosorbent assay (ELISA). The Childhood Autism Rating Scale (CARS) was used to assess the severity of autism as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). The Mann-Whitney U test was used for comparisons between children with autism and healthy children. The Spearman r correlation coefficient (r) was used to determine the relationship between the CARS scores among patients with autism and different variables. RESULTS: The mean plasma level of Arc/Arg3.1 protein in autism was 1.689 ± 0.917 pg/ml, significantly higher than that of healthy controls, i.e. 0.792 ± 1.056 pg/ml (p < 0.001). No significant relationship was found between plasma levels of Arc/Arg3.1 protein and CARS scores (r = -0.06; p > 0.05) or age (r = -0.27; p > 0.05). CONCLUSIONS: The mean plasma level of Arc/Arg3.1 protein was higher in children with autism than in controls, suggesting that Arc/Arg3.1 could be a potential early blood biomarker for diagnosis of autism.

Heart Rate Beat-to-Beat Slope Change during Six-Minute Walk Test: a Useful Clinical Tool for Estimating Fitness level.

BACKGROUND: The six-minute walk test (6MWT) is one of the most common exercise tests and is used to estimate the level of physical fitness. This study aimed to evaluate the feasibility of the beat-to-beat heart rate 6MWT slope (6MWTS) and recovery slope for predicting and estimating the level of physical fitness during 6MWT, instead of depending on the distance covered during the test. METHODS: Seventy healthy adult male subjects aged 18 to 27 years were recruited randomly from the general Saudi population in Riyadh. Using a 50-m corridor, 6MWT was performed according to standardised American Thoracic Society guidelines. RESULTS: The mean distance walked in 6 minutes (470.5±64.6 m) and beat-to-beat heart rate (HR) were calculated using a HR monitor. In addition, the body mass index, body surface area, Borg Rating of Perceived Exertion, and maximum predicted HR percentage were also calculated. A stepwise regression equation was used to predict the 6MWT distance (6MWTD), 6MWTS, and recovery slope. There was a significant correlation between 6MWTS and the recovery slope (r= -0.575, p<0.001), between 6MWTS and 6MWTD (r= 0.414, p<0.001), and between recovery slope and 6MWTD (r= -0.454, p<0.001). CONCLUSION: Our findings suggest that both 6MWTS and recovery slope can predict 6MWTD.