Research

Prospective Longitudinal Analysis of Immune Responses in Pediatric Subjects After Pharyngeal Acquisition of Group A Streptococci

Nicholas D. Hysmith, Edward L. Kaplan, P. Patrick Cleary, Dwight R. Johnson, Thomas A. Penfound, James B. Dale
Journal of Pediatric Infectious Disease Society-2017
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The prospective study examining the immunological response to infection by group A streptococcus (GAS) was performed in serum samples obtained from pediatric subjects. Study examined the immune response to 13 shared GAS antigens and 18 type-specific M peptides, but found no novel pattern of immune responses. Importantly, the study found that 65% of new streptococcus infections did not result in symptoms despite a detectable immunological response. This finding is supported by previous research and suggests that the majority of GAS infections remain undetected and contribute to the burden of the disease when left untreated.

Improvement of psychiatric symptoms in youth following resolution of sinusitis

Talia Mahony, Douglas Sidell, Hayley Gans, Kayla Brown, Bahare Farhadian, Melissa Gustafson, Janell Sherr, Margo Thienemann, Jennifer Frankovich
International Journal of Pediatric Otorhinolaryngology-2017

Improvement of psychiatric symptoms correlated with resolution of sinus disease in this retrospective study. Identification, treatment, and resolution of underlying infections, including sinusitis, may have the potential to change the trajectory of some neuropsychiatric illnesses.

The neuropsychological profile of children with basal ganglia encephalitis: a case series

Pawela C, Brunsdon RK, Williams TA, Porter M, Dale RC, Mohammad SS
Dev Med Child Neurol-2016
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Although based on a small, cross‐sectional case series, our results highlight the potential importance of early identification and IVIg treatment of BGE. Given the cognitive and behavioural deficits described in this report, our clinical recommendation would be to try to treat patients rapidly with immune therapies, when clinical suspicion of BGE is high, to minimize the inflammatory component of the disease.

Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease
Uhde M, Ajamian M, Li X, Wormser GP, Marques A, Alaedini A. Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease. Clin Infect Dis. 2016 Dec 1;63(11):1399-1404. doi: 10.1093/cid/ciw599. Epub 2016 Sep 1. PMID: 27585799; PMCID: PMC5106611.

The immune response to invasive microbes involves two main components: the innate and adaptive response. C-reactive protein (CRP) and serum amyloid A (SAA) are proteins elevated during inflammation. In Lyme disease, CRP is elevated in early stages with erythema migrans but normal in neurological symptoms and arthritis. However, post-treatment Lyme disease syndrome (PTLDS) shows higher CRP, indicating persistent inflammation. SAA is elevated only in patients with erythema migrans. These findings suggest that lingering symptoms post-antibiotic therapy in Lyme disease are associated with elevated CRP, warranting further study on long-term inflammatory processes.

Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections

Kyle A. Williams, MD, PhD, Susan E. Swedo, MD, Cristan A. Farmer, PhD, Heidi Grantz, LCSW, Paul J. Grant, MD, Precilla D’Souza, CRNP, Rebecca Hommer, MD, Liliya Katsovich, MA, Robert A. King, MD, James F. Leckman, MD, Phd
Journal of the American Academy of Child & Adolescent Psychiatry–2016

IVIG was safe and well tolerated. Between-group differences were smaller than anticipated, and the double-blind comparison failed to demonstrate superiority of IVIG over placebo. The observed open-label improvements indicate that future trials would benefit from larger sample sizes designed in part to aid in the identification of biomarkers predictive of a positive response to immunotherapy. Future investigations focused on the natural history of PANDAS are also warranted.

Microglial Dysregulation in OCD, Tourette Syndrome, and PANDAS
Luciana Frick, Christopher Pittenger, “Microglial Dysregulation in OCD, Tourette Syndrome, and PANDAS”, Journal of Immunology Research, vol. 2016, Article ID 8606057, 8 pages, 2016. https://doi.org/10.1155/2016/8606057

Mechanisms by which microglial abnormalities contribute to disease are likely to be shared across distinct etiologies and traditional diagnoses. For instance, abnormal synaptic pruning was observed both in animals inoculated with GAS (which may capture key elements of the pathophysiology of PANDAS) and in mice that develop excessive grooming after inactivation of the progranulin gene. In both cases, increased synaptic pruning cooccurs with microglia activation.

Pediatric Autoimmune Disorders Associated with Streptococcal Infections and Tourette’s Syndrome in Preclinical Studies

Chiara Spinello, Giovanni Laviola and Simone Macrì
Frontiers in Neuroscience – 2016
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In the present review we discuss the available evidence in preclinical models in support of the link between TS and pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS), and the existing gaps that future research shall bridge. Specifically, we report recent preclinical evidence indicating that the immune responses to repeated streptococcal immunizations relate to the occurrence of behavioral and neurological phenotypes reminiscent of TS.