scholarly journals THE RESULTS OF THE SEARCH FOR LABORATORY SIGNS OF AUTOIMMUNE REACTIONS TO CEREBRAL AND EXTRACEREBRAL AUTOANTIGENS IN CHILDREN WITH AUTISM SPECTRUM DISORDERS ASSOCIATED WITH GENETIC DEFICIENCY OF THE FOLATE CYCLE

2021 ◽  
Vol 17 (3) ◽  
pp. 22-37
Author(s):  
D.V. Maltsev

Relevance. The results of five meta-analyzes of randomized controlled clinical trials indicate an association between genetic deficiency of the folate cycle (GDFC) and autism spectrum disorders (ASD) in children. Autoimmune mechanisms play a special role in the pathogenesis of encephalopathy in children with ASD associated with GDFC. Objective: to study the structure of autoimmune reactions in children with ASD associated with GDFC, according to the accumulated evidence base and to identify associations of laboratory signs of autoimmunity and microorganisms to improve understanding of encephalopathy pathogenesis and diagnostic, monitoring and treatment algorithms. Materials and methods. The medical data of 225 children aged 2 to 9 years with GDFC, who had clinical manifestations of ASD (183 boys and 42 girls) were retrospectively analyzed. The diagnosis of ASD was made by child psychiatrists according to the criteria DSM-IV-TR (Diagnostic and Statistical Manual of mental disorders) and ICD-10 (The International Statistical Classification of Diseases and Related Health Problems) (study group; SG). The control group (CG) included 51 clinically healthy children (37 boys and 14 girls) of similar age and gender distribution who did not suffer from GDFC and ASD. Pathogenic polymorphic variants of folate cycle genes were determined by PCR with restriction (Sinevo, Ukraine). Autoantibodies to autoantigens of CNS subcortical ganglion neurons in blood serum were determined using a Cunningham panel (Moleculera Labs, Inc, USA). Serum autoantibodies to neurons of the mesolimbic system of the brain were identified by ELISA (MDI Limbach Berlin GmbH, Germany). Autoimmunization to myelin was assessed by serum autoantibody titer to basic myelin protein (ELISA) and signs of neutrophil and CD8+ T-lymphocyte sensitization to hemispheric white matter autoantigens (cell-based assay; department of neuroimmunology at the Neurosurgery Institute; Ukraine). Serum autoantibodies to nuclei of connective tissue cells and striated muscle proteins were determined by western blot analysis (Sinevo, Ukraine). To determine the significance of the differences between the indicators in the observation groups, we used the Student's parametric T-test with the confidence probability p and the nonparametric criterion – the number of signs Z according to Urbach Yu.V. The odds ratio (OR) and the 95% confidence interval (95% CI) were used to study the associations between the studied indicators. The study was performed as a fragment of research work commissioned by the Ministry of Health of Ukraine (№ state registration 0121U107940). Research. Positive results of the Cunningham panel occurred in 32%, laboratory signs of autoimmunization to neurons of the mesolimbic system – 36%, myelin of white matter of the hemispheres – 43%, nuclei autoantigens of connective tissue cells – 53%, proteins of striated muscles – 48% of cases among children SG (in general – 68% of cases; p < 0.05; Z < Z0.05). Serological signs of autoimmunization to autoantigens of the subcortical ganglia of the cerebral hemispheres were associated with Streptococcus pyogenes and Borrelia, to neurons of the mesolimbic system – EBV, HHV-6, HHV-7, Toxoplasma and TTV, to CNS myelin – EBV, HHV-6, HHV-7, Borrelia and TTV, to the nuclei of connective tissue cells and striated muscles – EBV, HHV-6, HHV-7, Borrelia and TTV. Conclusions. In children with ASD associated with GDFC laboratory sings of microbial-induced autoimmunity to a number of cerebral and extracerebral autoantigens has been evaluated, which affects the mental and physical health of patients and is a potential target for effective therapeutic interventions.

2021 ◽  
Vol 20 (2) ◽  
pp. 211-216
Author(s):  
Dmitry Maltsev ◽  
◽  
Volodymyr Stefanyshyn ◽  

Objectives. The results of previous small clinical trials indicate the potential benefit of combination immunotherapy with Propes and Inflamafertin to compensate for NK and NKT cell deficiency due to genetic deficiency of the folate cycle in children with autism spectrum disorders. The purpose of the research was to study the effectiveness of combined immunotherapy with Propes and Inflamafertin in NK and NKT cell deficiency in children with autism spectrum disorders associated with genetic deficiency of the folate cycle. Material and methods. This single-center, prospective, controlled, nonrandomized clinical trial included 96 children aged 2 to 10 years with autism spectrum disorders associated with a genetic folate deficiency (study group, SG). Children of SG received Propes at a dose of 2 ml IM every other day for 3 consecutive months (45 injections), and Inflamafertin at a dose of 2 ml IM every other day for 3 months in a row, alternating with Propes (45 injections). The control group (CG) consisted of 32 children of similar age and gender distribution who suffered from autism spectrum disorders associated with genetic deficiency of the folate cycle, but who did not receive immunotherapy. Outcomes. The number of NK cells reached the lower limit of normal in 39 out of 53 patients (74% of cases), with the resulting deficiency of these lymphocytes, and the average number of NK cells in the blood in SG almost doubling during the 3-month course of immunotherapy (р ˂ 0.05; Z ˂ Z0.05). However, it returned to almost initial level in the 2 months following the discontinuation of immunotherapeutic agents (р˃0.05; Z˃Z0.05). The number of NKT cells was normalized in 78 out of 87 patients (89% of cases) with an initial deficiency of these cells, and the average number of NKT cells in the blood in the DG increased during the course of immunotherapy by half (р ˂ 0.05; Z ˂ Z0.05) and continued to grow for the next 2 months after the discontinuation of immunotropic drugs (р ˂ 0.05; Z ˂ Z0.05). There was a link between immunotherapy and normalization of NK - (χ2 = 18.016; OR = 13.929; 95%CI = 3.498-55.468) and NKT-cells (χ2 = 60.65; OR = 46.800; 95%CI = 14.415-151.937) in the blood with a strong association between these processes (criterion φ = 0.504 and 0.715 respectively; С = 0.450 and 0.581 respectively). Conclusions. Combination immunotherapy with Propes and Inflamafertin is an effective strategy for the treatment of immunodeficiency caused by genetic deficiency of the folate cycle in children with autism spectrum disorders.


2020 ◽  
Vol 19 (4) ◽  
pp. 737-742
Author(s):  
DmitryV Maltsev

Aim: to show the effect of genetically determined folate cycle deficiency in children with autism spectrum disorders (ASD). Participants: 89 children (57 boys; 32 girls, Ukraine, 2-10 years old); participants were diagnosed with ASD. The control group consisted of 34 children with ASD. Diagnostic methods:polymerase chain reaction (PCR), complex immunological research, diagnosis of infection, determination of biomarkers. Results and discussion:Hyperhomocysteinemia was revealed in 87% of cases (p <0.05; Z <Z0.05).The indicated form of immunodeficiency was noted among 91% participants in the study, while only in 27% children of the control group had a similar immunological phenotype.The serum concentration of folic acid was increased in 64%, and reduced in 21% of cases. An increase of vitamin B12 also occurred in 64%, and vitamin B6 - only in 43% of cases. Bangladesh Journal of Medical Science Vol.19(4) 2020 p.737-742


2010 ◽  
Vol 20 (2) ◽  
pp. 42-50 ◽  
Author(s):  
Laura W. Plexico ◽  
Julie E. Cleary ◽  
Ashlynn McAlpine ◽  
Allison M. Plumb

This descriptive study evaluates the speech disfluencies of 8 verbal children between 3 and 5 years of age with autism spectrum disorders (ASD). Speech samples were collected for each child during standardized interactions. Percentage and types of disfluencies observed during speech samples are discussed. Although they did not have a clinical diagnosis of stuttering, all of the young children with ASD in this study produced disfluencies. In addition to stuttering-like disfluencies and other typical disfluencies, the children with ASD also produced atypical disfluencies, which usually are not observed in children with typically developing speech or developmental stuttering. (Yairi & Ambrose, 2005).


2020 ◽  
Author(s):  
Jason He ◽  
Ericka Wodka ◽  
Mark Tommerdahl ◽  
Richard Edden ◽  
Mark Mikkelsen ◽  
...  

Alterations of tactile processing have long been identified in autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). However, the extent to which these alterations are disorder-specific, rather than disorder-general, and how they relate to the core symptoms of each disorder, remains unclear. We measured and compared tactile detection, discrimination and order judgment thresholds between a large sample of children with ASD, ADHD, ASD + ADHD combined and typically developing controls. The pattern of results suggested that while difficulties with tactile detection and order judgement were more common in children with ADHD, difficulties with tactile discrimination were more common in children with ASD. Strikingly, subsequent correlation analyses found that the disorder-specific alterations suggested by the group comparisons were also exclusively related to the core symptoms of each respective disorder. These results suggest that disorder-specific alterations of lower-level sensory processes exist and are specifically related to higher-level clinical symptoms of each disorder.


Author(s):  
Dominique H. Como ◽  
Leah I. Stein Duker ◽  
José C. Polido ◽  
Sharon A. Cermak

Children with autism spectrum disorders (ASD) are at risk for oral health disparities. With the dramatic rise in ASD prevalence to 1 in 54 children, it is likely that an increasing number of dental practitioners will encounter or be asked to treat children with ASD. This paper reviews explanations related to the increasing prevalence of ASD, provides reasons why children with ASD are at increased risk for poor oral health, and discusses unique interprofessional collaborations between dental practitioners and occupational therapists. Occupational therapists and dentists can work together to plan modifications to the dental environment or adapt dental protocols to reduce some of the barriers encountered by those with ASD, provide desensitization strategies before the clinic visit, or help a child with emotional regulation during clinical treatments.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Mohammad Ali Ghaffari ◽  
Elham Mousavinejad ◽  
Forough Riahi ◽  
Masoumeh Mousavinejad ◽  
Mohammad Reza Afsharmanesh

Background. Autism spectrum disorders (ASDs) are complex disorders where the pathogenesis is not fully understood. Several proinflammatory and immunoinflammatory disturbances have been observed in the etiology of ASD. There is, however, limited knowledge on variations of adipokines in ASD. The present study aimed to analyze the serum levels of resistin, visfatin, and tumor necrosis factor-alpha (TNF-α) in children with ASD in relation to body weight, gender, and ASD severity level. Method. In total, 30 children with ASD (mean age: 7.72±2.65 y; range; 4–12 y) and 30 healthy children (mean age: 8.4±2.66 y; range: 4–12 y), including males and females, were matched for age, gender, and body mass index (BMI). Serum samples were collected, and visfatin, resistin, and TNF-α serum levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Result. Serum visfatin, resistin, and TNF-α levels in children with ASD were significantly higher than that in the healthy patients (p<0.05). Two significant correlations were found: a correlation between resistin and visfatin with TNF-α in children with ASD (R = 0.8 and R = 0.62, resp.) and a correlation between resistin and visfatin in children with ASD (R = 0.66). Conclusion. Higher TNF-α, resistin, and visfatin levels were found in children with ASD in comparison with controls, suggesting that elevated levels of serum proinflammatory agents may be implicated in the pathophysiology of ASD.


2017 ◽  
Vol 41 (S1) ◽  
pp. S214-S214 ◽  
Author(s):  
L. Kobylinska ◽  
C.G. Anghel ◽  
I. Mihailescu ◽  
F. Rad ◽  
I. Dobrescu

Children with autism spectrum disorders (ASD) have a less definitive hand preference for certain actions as opposed to neurotypical children. Moreover, left-handedness in children with ASD has been associated with more echolalia. The objective was to conduct a screening of potential risk and associated features for autism spectrum disorders, among which the hand preference of the child. The current aim is to compare the perceived handedness of children with autism spectrum disorders with that of children with other psychiatric pathologies.MethodsEight hundred and forty-two parents completed our risk and associated features screening questionnaire. Out of these, 494 answered the question regarding handedness (209 had children diagnosed with ASD). This asked the parents to state how they perceived their child's handedness. An ADOS assessment has been conducted for 170 of the children whose parents were included in the study, based on clinical relevance for the case. The data were analysed using Excel and SPSS 22.0. For the comparisons, Chi2 and the Kruskal–Wallis test were used.ResultsChildren with ASD had more left-handedness (χ2(2) = 12.54, P = 0.002). There were no differences between boys and girls in terms of perceived handedness in any of the groups. There were no differences in the ADOS scores according to the perceived hand laterality (χ2(2) = 0.58, P = 0.74).ConclusionRightward-asymmetry in regions of corpus callosum has been reported to correlate with symptoms severity in ASD. The finding of different perceived handedness in children with ASD versus children with other psychiatric pathologies is useful for designing appropriate, individualized training programs for motor therapy.Disclosure of interestThe authors have not supplied their declaration of competing interest.


Author(s):  
Sarah N. Douglas ◽  
Yan Shi ◽  
Saptarshi Das ◽  
Subir Biswas

Children with autism spectrum disorders (ASD) struggle to develop appropriate social skills, which can lead to later social rejection, isolation, and mental health concerns. Educators play an important role in supporting and monitoring social skill development for children with ASD, but the tools used by educators are often tedious, lack suitable sensitivity, provide limited information to plan interventions, and are time-consuming. Therefore, we conducted a study to evaluate the use of a sensor system to measure social proximity between three children with ASD and their peers in an inclusive preschool setting. We compared video-coded data with sensor data using point-by-point agreement to measure the accuracy of the sensor system. Results suggest that the sensor system can adequately measure social proximity between children with ASD and their peers. The next steps for sensor system validation are discussed along with clinical and educational implications, limitations, and future research directions.


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