Pediatric Autoimmune Neuropsychiatric Disorders Associated With Group A Streptococci: Etiopathology and Diagnostic Challenges

Hutanu, Andrada; Reddy, Lalitha N; Mathew, Janice; Avanthika, Chaithanya; Jhaveri, Sharan; Tummala, Nayanika

doi:10.7759/cureus.27729

Cited by 7 publications

(5 citation statements)

References 70 publications

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“…Another possible example of the mistaken identification of stealth adapted virus infections as a bacteria-induced illness is PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). 48,49 From personal experience in reviewing laboratory testing data, it is not uncommon for there to be either anti-Streptolysin O (ASO) or anti-DNase B antibody but not both, as would be expected if there were an infection with viable bacteria. Positive Lyme disease serology has also been reported in association PANDAS.…”

Section: Introduction and Discussionmentioning

confidence: 99%

Stealth adapted viruses can incorporate renegade cellular and bacterial genetic sequences: public health implications

Wj¹

2023

JHVRV

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The cellular immune system normally responds to relatively few of the different structural components that comprise the complete virus. Mutation or deletion of the genes coding for these few antigenic components is an immune evasion mechanism termed “stealth adaptation.” I initially used this term to describe a virus derived from an African green monkey simian cytomegalovirus (SCMV). This article provides an extended discussion of the Public Health relevance of previously reported findings relating to this virus. Of particular significance, the virus did not evoke inflammation in the chronic fatigue syndrome (CFS) patient from whom the virus was repeatedly cultured, nor in virus inoculated animals. The viral genome consists of multiple fragments of double stranded DNA with lengths of approximately twenty thousand nucleotides (20 kb). This is in marked contrast to the >226 kb size of the normal SCMV genome. Purified virus DNA was cloned, and sequence data were subsequently obtained. Most of the cloned sequences match to regions corresponding in their entirety to only approximately half of the originating SCMV genome. These matching sequences are very unevenly distributed along the SCMV genome. Moreover, there are significant genetic sequence differences between clones matching to identical regions of the SCMV genome. In addition to the SCMV matching sequences, there are sequences that match to regions of the human genome. There are also sequences that match closely to genes of bacterial origin. The major sources of the bacterial sequences in the initially cultured stealth adapted virus are from Mycoplasma fermentans and Ochrobactrum quorumnocens bacteria. These findings have extended the generic concept of stealth adaptation to include not only the loss or mutation of portions of the originating virus genome, which would have otherwise resulted in cellular immune recognition, but also the potential incorporation/acquisition of additional “renegade” genetic sequences from cellular genes and from other microbial genomes. The apparent acquisition of cellular genetic sequences by stealth adapted viruses may potentially lead to the infectious transmission of genetically determined illnesses. The inclusion of bacterial sequences is also concerning since it indicates possible bacteria mediated transmission of infectious stealth adapted viruses. Furthermore, the transmissible bacterial sequences can potentially result in the mistaken diagnosis of a stealth adapted virus infection for a bacterial disease. Examples are likely to include chronic Lyme disease and PANDAS, a severe childhood psychiatric illness. Public Health officials should respond urgently to the existence of stealth adapted viruses.

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Section: Introduction and Discussionmentioning

confidence: 99%

Stealth adapted viruses can incorporate renegade cellular and bacterial genetic sequences: public health implications

Wj¹

2023

JHVRV

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“…First, TNFB regulates the formation of tertiary lymphoid-like structures [ 178 , 179 ], such as the murine nasal-associated lymphoid tissue (NALT) [ 180 ] that is analogous to the human tonsils/adenoids [ 181 ]. Group A streptococcal (GAS) bacteria that are present in both mouse NALT and human tonsils [ 182 ] are crucial in the pathophysiology of PANDAS, an auto-immune disease that presents itself as a combination of tics and OCD-like symptoms [ 183 ]. In addition, streptococcal superantigens—that are involved in PANDAS [ 184 ]—directly stimulate the secretion of TNFB [ 185 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Landscape of Tourette’s Disorder

Widomska

Witte

Buitelaar

et al. 2023

IJMS

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Tourette’s disorder (TD) is a highly heritable childhood-onset neurodevelopmental disorder and is caused by a complex interplay of multiple genetic and environmental factors. Yet, the molecular mechanisms underlying the disorder remain largely elusive. In this study, we used the available omics data to compile a list of TD candidate genes, and we subsequently conducted tissue/cell type specificity and functional enrichment analyses of this list. Using genomic data, we also investigated genetic sharing between TD and blood and cerebrospinal fluid (CSF) metabolite levels. Lastly, we built a molecular landscape of TD through integrating the results from these analyses with an extensive literature search to identify the interactions between the TD candidate genes/proteins and metabolites. We found evidence for an enriched expression of the TD candidate genes in four brain regions and the pituitary. The functional enrichment analyses implicated two pathways (‘cAMP-mediated signaling’ and ‘Endocannabinoid Neuronal Synapse Pathway’) and multiple biological functions related to brain development and synaptic transmission in TD etiology. Furthermore, we found genetic sharing between TD and the blood and CSF levels of 39 metabolites. The landscape of TD not only provides insights into the (altered) molecular processes that underlie the disease but, through the identification of potential drug targets (such as FLT3, NAALAD2, CX3CL1-CX3CR1, OPRM1, and HRH2), it also yields clues for developing novel TD treatments.

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“…Some infections (like group A streptococcus -GAS) can cause sudden, mixed, movement (such as Sydenham's chorea) and mental disorders such as obsessive-compulsive disorders (OCD), tic disorder, ADHD in children. This has made researchers look at infective agents as possible triggers of childhood neurodevelopmental disorders, affecting basal ganglia [5][6][7]. A molecular mimicry mechanism might explain why the symptoms last even after GAS infection is gone [8].…”

Section: Introductionmentioning

confidence: 99%

The Prevalence of Streptococcal Infection and Anti-Basal Ganglia Antibodies in ADHD Pediatric Patients

Ahmed

2024

Int J Chem Biochem Sci

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Children who have trouble paying attention, controlling their impulses, or being hyperactive may suffer from attention-deficit/hyperactivity disorder (ADHD), a mental health condition that is largely influenced by their genes. However, other factors in their surroundings, such as exposure to certain bacteria or toxins, may also play a role in triggering or worsening their symptoms. In our study, we wanted to find out how common it is for children with ADHD to have an infection caused by a type of bacteria called group A streptococcus (GAS), and how often they have antibodies against GAS (ABGA) in their blood, which may indicate a past or ongoing infection. 60 children took part in a trial that was open, controlled, and random. They were split into two equal groups: group A had children with ADHD and group B had healthy children. We collected their demographic data such as age, sex, and ADHD risk factors. Group A had children with ADHD. Only depression was much higher in GAS+children than GAS-children (P=0.035). Other factors like attention, impulsiveness, non-planning, motor and fine motor speed were not different between GAS+ and GAS-children. Group B had healthy children. Impulsiveness and depression were much higher in GAS+children than GAS-children (P=0.001, 0.001). Other factors like attention, non-planning, motor, and fine motor speed were not different between GAS+ and GAS- children. ADHD children had more infections, GAS, and antibodies than healthy children. GAS+ADHD children had more depression than GAS-ADHD children. ADHD children had more attention, impulsiveness, and fine motor problems.

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Pediatric Autoimmune Neuropsychiatric Disorders Associated With Group A Streptococci: Etiopathology and Diagnostic Challenges

Cited by 7 publications

References 70 publications

Stealth adapted viruses can incorporate renegade cellular and bacterial genetic sequences: public health implications

Stealth adapted viruses can incorporate renegade cellular and bacterial genetic sequences: public health implications

Molecular Landscape of Tourette’s Disorder

The Prevalence of Streptococcal Infection and Anti-Basal Ganglia Antibodies in ADHD Pediatric Patients

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