Association between pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections disease and tumor necrosis factor-α gene−308 g/a, −850 c/t polymorphisms in 4-12-year-old children in Adana/Turkey

Abstract

OBJECTIVES:Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a newly defined disease in neuropsychiatry and occurs with an autoimmune mechanism after Group A Beta Hemolytic Streptococcus (GABHS) infection. Tumor necrosis factor (TNF), encoded by TNF-α gene has an important role in the apoptotic mechanisms of autoimmune diseases. Recently, TNF-α polymorphisms and autoimmune/psychiatric disorders have been reported to be related. In this regard, we focused on to investigate a possible relation between the TNF-α gene promoter region−308 G/A and − 850 C/T polymorphisms and PANDAS.MATERIALS AND METHODS:In this study, ages of PANDAS patient and control groups were ranging from 4 years to 12-year-old. Patient group includes childhood onset PANDAS patients (n = 42) and control group includes healthy children (n = 58). Diagnoses have been carried out according to Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) criteria with Affective Disorders and Schizophrenia-Present and Lifetime (KSAD-S-PL) and Children Yale-Brown Obsessive Compulsive Scale Moreover, PANDAS criteria established by the American National Psychiatry Institute have been employed for diagnoses. For identifying polymorphisms; Polymerase Chain Reaction, Restriction Fragment Length Polymorphism and Polyacrylamid Gel Electrophoresis were used.RESULTS AND DISCUSSION:For −308 polymorphism, 37 of 42 PANDAS patients’ results and for −850 C/T polymorphism, 38 of 42 PANDAS patients’ results were obtained. According to our statistical analysis there is a positive relationship between PANDAS patients for −308 G/A polymorphism but not for −850 C/T polymorphism. There is no positive relationship between −308 G/A polymorphism and antistrep-tolysin O (ASO) titers and no relationship between −850 C/T polymorphism and ASO titers. We found, however, positive relationship between genders of patients (boys) and the disease. According to our results, we propose that the AA polymorphism of −308 G/A polymorphism can be used as a molecular indicator for PANDAS.

Alterations in the Nervous System and Gut Microbiota after β-Hemolytic Streptococcus Group A Infection—Characteristics and Diagnostic Criteria of PANDAS Recognition

“…This might have an indirect impact on behavior due to the reduced production of various metabolites involved in brain functions. Further, exon variants of the MBL gene and altered levels of TNF-α increase the susceptibility of PANDAS [67,68]. The treatment of PANDAS syndrome is still not obvious and specified, however, there are several alternatives that show promising results.…”

“…Therefore, the MBL2 gene is suspected to be one of the diagnostic markers of PANDAS. According to Luleyap et al, TNF-α −308 AA polymorphism can be regarded as a molecular indicator of PANDAS [68]. Altered levels of TNF-α can be associated with exacerbation of PANDAS symptoms and facilitating autoimmune responses within the central nervous system.…”

CNS Autoimmune Disease after Streptococcus Pyogenes Infections: Animal Models, Cellular Mechanisms and Genetic Factors

“…To date, only a single, small molecular genetic study has been published for PANDAS, demonstrating a positive association between one genetic polymorphism (308 G/A – rs1800629) in the TNF- α promoter for PANDAS patients, using a hospital-based case-control study of 42 children with PANDAS and 58 healthy controls [66]. There was, however, no positive relationship between this 308 G/A polymorphism and anti-streptolysin O (ASO) titers, a serological indication of previous S. pyogenes infections.…”

Effect of Early and Prophylactic Nonsteroidal Anti-Inflammatory Drugs on Flare Duration in Pediatric Acute-Onset Neuropsychiatric Syndrome: An Observational Study of Patients Followed by an Academic Community-Based Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic

“…In addition, a positron emission tomography (PET) imaging study found greater microglial activation in patients with PANDAS compared with controls (Kumar et al 2015). Another study found an association between the tumor necrosis factor (TNF)-a gene -308G/A polymorphism and patients with PANDAS (Luleyap et al 2013). A recent animal model designed to evaluate the relationship between nasopharyngeal infection and neuroinflammation showed that multiple intranasal infections with live GAS generate GAS-specific Th17 cells that migrate along olfactory sensory axons into the brain.…”