Research

Cellular Mechanisms of Neurovascular Breakdown and Neuronal Dysfunction Following Recurrent Group A Streptococcus Infections in Mice

Platt, Maryann P.
Columbia Academic Commons-2019 Theses Doctoral

Taken together, these data demonstrate the pivotal role of Th17 lymphocytes in brain pathology and olfactory processing deficits after recurrent GAS infections in our mouse model. Our intranasal inoculation model supports the conclusion that post-infectious BGE is autoimmune in nature, despite the absence of behavioral symptoms in this model. Using multiple mouse models of post-infectious BGE may allow us to study distinct facets of disease pathogenesis. Finally, this work underscores the ability of T cells to incite neuroinflammation, provides a useful clinical diagnostic test in olfactory functional assessments, and lends support to T cell immunotherapy strategies in patients with post-infectious BGEs.

Molecular Mimicry, Autoimmunity, and Infection: The Cross-Reactive Antigens of Group A Streptococci and their Sequelae

Madeleine W. Cunningham
Microbiology Spectrum-August 2019
Author manuscript – In advance of print

The studies suggest 1) that the antibodies against streptococci and brain in Sydenham chorea and related diseases produce CNS dysfunction through a neuronal signal transduction and subsequent excess dopamine release mechanism and 2) that the molecular targets of the chorea antibodies include lysoganglioside and the dopamine receptors in neuronal cell membranes. The anti-neuronal autoantibodies also target the group A streptococcal carbohydrate epitope N-acetyl beta-D-glucosamine present on the rhamnose backbone of the carbohydrate and present in the cell membrane and wall of the group A streptococci as well as the intracellular brain protein tubulin. The diagram in Figure 15 illustrates proposed events of how antineuronal autoantibodies against lysoganglioside and the dopamine receptors D1 and D2 may function in Sydenham chorea and PANDAS (3).

Obsessive-Compulsive Disorder: Autoimmunity and Neuroinflammation

Mona Gerentes, Antoine Pelissolo, Krishnamoorthy Rajagopal, Ryad Tamouza, Nora Hamdani,
Anxiety Disorders-August 2019

This review highlights that OCD is associated with low-grade inflammation, neural antibodies, and neuro-inflammatory and auto-immune disorders. In some subset of OCD patients, autoimmunity is likely triggered by specific bacterial, viral, or parasitic agents with overlapping surface epitopes in CNS. Hence, subset-profiling in OCD is warranted to benefit from distinct immune-targeted treatment modalities.

The role of infections in autoimmune encephalitides

B. Joubert, J.Dalmau
International meeting of the French society of neurology & SPILF 2019

Abstract: Autoimmune encephalitides are autoimmune neurological disorders characterized by rapidly progressive central nervous system symptoms associated with specific auto-antibodies targeting neuronal cell-surface proteins. The clinical features of encephalitis are frequently preceded by symptoms suggesting an infectious process, and specific pathogens have been detected at the early phase of the disease in some patients, suggesting that it can be triggered by infections. Moreover, recent data have shown an association with specific HLA haplotypes, suggesting a genetic susceptibility to develop at least some subtypes of autoimmune encephalitis. Nonetheless, the immunological mechanisms leading from an adequate response to infection to autoimmunity against neuronal self-antigens remain highly hypothetical. Molecular mimicry, inborn errors of the host immune system, as well as epitope spreading and chronic activation of innate immunity actors, may be involved. Importantly, the frequency of prodromal infectious symptoms and association with HLA haplotypes differ among autoimmune encephalitides, suggesting that depending on the subtype distinct immunopathogenic mechanisms are involved. A direct link between infection and autoimmune encephalitis was recently provided by the demonstration that most of the so-called relapsing neurological symptoms post-herpes simplex virus encephalitis corresponded to viral-induced autoimmune encephalitis with antibodies against NMDA receptors or other, yet unknown, neuronal surface antigens. Although this association has also been demonstrated experimentally in mice, the underlying immunological mechanisms remain unknown. Overall, a body of clinical, epidemiological and experimental data suggests infections are involved in the pathogenesis of autoimmune encephalitides. Further studies, focusing on the interplays between pathogens, genetic determinants of the host immune response, and brain inflammation, are needed to clarify the immunological mechanisms that lead to autoimmune encephalitis after infection.

ENT involvement and orobuccal movements’ disorders in Pandas patients: assessment and rehabilitations tools

S. Cocuzza, S. Marino, A. Gulino, E. Pustorino, P. Murabito, A. Maniaci, L. Sabino, R. Taibi, M. Di Luca, R. Falsaperla, G. Campione, M. Vecchio, P. Pavone
Eur Rev Med Pharmacol Sci-2019

Findings from our study show that respiratory diseases, characterizing a group of patients with pandas, are the direct consequences of the malformed or hypertrophic condition and suggesting in these conditions surgical therapy as an approaching tool.

Altered frequencies of Th17 and Treg cells in children and adolescents with obsessive-compulsive disorder

Natalia Rodrígueza, Astrid Morerbgh, Azucena González-Navarrocg, Carles Serra-Pages, Daniel Bolo, Teresa Torrese, Albert Martinez-Pinteñoe, Sergi Ma, Amalia Lafuenteegh, Patricia Gassóeg, LuisaLázarobdgh
Brain, Behavior, and Immunity-2019

Highlights
•Th17 cells are increased in children and adolescents with OCD.
•Percentages of Treg cells are reduced in OCD patients.
•Increased levels of Th17 cells are associated with higher severity of OCD symptoms.
•Increased levels of Th17 cells are associated with longer duration of disease.
•Reduced percentatges of Treg cells are associated with longer duration of disease.

Association of Streptococcal Throat Infection With Mental Disorders Testing Key Aspects of the PANDAS Hypothesis in a Nationwide Study

Sonja Orlovska, MD; Claus Høstrup Vestergaard, MS; Bodil Hammer Bech, PhD; Merete Nordentoft, DrMed; Mogens Vestergaard, PhD; Michael Eriksen Benros, PhD
JAMA Psychiatry-2017

The findings reported in this research study represent one of the largest retrospective studies conducted to date on the association between streptococcal infections and PANDAS. Children with a previously positive streptococcus test had an 18% higher risk of any mental disorder, 51% higher risk of OCD, and 35% higher risk of tic disorders, which are diagnostic criteria for PANDAS. Study findings support the association of streptococcal and non-streptococcal infections in the diagnosis of pediatric acute-onset neuropsychiatric syndrome.

A Pediatric Infectious Disease Perspective on Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection and Pediatric Acute-Onset Neuropsychiatric Syndrome

Wald, Ellen
The Pediatric Infectious Disease Journal-2019

In 2013, a PANS Consensus Conference was convened at Stanford University, and several consensus statements have been published in recent years. The existence of PANDAS has been controversial from the time of its first publication. For those of us familiar with the sequelae of streptococcal disease and the concerns of community physicians faced with the care of children with these neuropsychiatric symptoms, the controversy has proven to be a disservice to both pediatricians and families. It has fostered a dismissive attitude toward important clinical observations.

Clinical-Serological Characterization and Treatment Outcome of a Large Cohort of Italian Children with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection and Pediatric Acute Neuropsychiatric Syndrome

Gemma Lepri, Donato Rigante, Silvia Bellando Randone, Antonella Meini, Alessandra Ferrari, Giusyda Tarantino, Madeleine W. Cunningham,Fernanda Falcini
JCAP-2019

Our study has confirmed the usefulness of the preliminary diagnostic criteria for PANDAS and PANS, revealing also the importance of early diagnosis to reduce the risk of evolution toward disabling chronic neurologic sequelae. Long-term antibiotic prophylaxis has resulted in a substantial benefit to reduce neurological symptoms for the majority of PANDAS and PANS patients over a 7-year period.

Association of Exposure to Infections in Childhood With Risk of Eating Disorders in Adolescent Girls

Lauren Breithaupt, Ole Köhler-Forsberg, Janne Tidselbak Larsen
JAMA Psychiatry-2019

Findings: In a Danish population-based cohort study of 525 643 adolescent girls, a prior infection in childhood was associated with an increased risk of later anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified.
Meaning: The findings suggest that prior exposure to infections and treatment with anti-infective agents are associated with the development of eating disorders, supporting an emerging immunologic hypothesis.