Research

Chain Jennifer L., Alvarez Kathy, Mascaro-Blanco Adita, Reim Sean, Bentley Rebecca, Hommer Rebecca, Grant Paul, Leckman James F., Kawikova Ivana, Williams Kyle, Stoner Julie A., Swedo Susan E., Cunningham Madeleine W. Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections. Jnl Frontiers in Psychiatry. Vol.11, 2020. DOI.10.3389/fpsyt.2020.00564   

See Dr. Susan Swedo on new research on Autoantibody Biomarkers for Basal Ganglia Encephalitis for PANDAS and SC

Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity Jian Xu, Rong-Jian Liu, Shaylyn Fahey, Luciana Frick, James Leckman, Flora Vaccarino, Ronald S. Duman, Kyle Williams, Susan Swedo, and Christopher Pittenger. Am Jrnl of Psychiatry 16 Jun 2020 https://doi.org/10.1176/appi.ajp.2020.19070698

See ASPIRE’s interview with Christopher Pittenger, MD, PhD, FAPA, FANA on this study.

Viral Pandemics as Possible Psycho-immunological Causes of Psychiatric Symptoms: From Past to Present

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Aytac HM, Pehlivan S. Viral Pandemics as Possible Psycho-immunological Causes of Psychiatric Symptoms: From Past to Present. Sağlık Bilimlerinde İleri Araştırmalar Dergisi 2020; 3(Suppl.1): S92-S98. https://doi.org/10.26650/JARHS2020-S1-0012

Benefits of IVIG in Pediatric Acute-Onset Neuropsychiatric Syndrome (2411)

Isaac Melamed, Roger Kobayashi, Maeve O’Connor, Ai Lan Kobayashi, Andrew Schechterman, Melinda Heffron, Sharon Canterberry, Holly Miranda, Nazia Rashid Neurology Apr 14 2020, 94

“Conclusions: In PANS, which may be associated with an underlying immune dysregulation, IVIG [Octagam 5%] successfully ameliorated psychological symptoms and dysfunction, with sustained benefits for at least 8 weeks, and up to 46 weeks, following the final infusion. In addition, baseline immune and autoimmune profiles demonstrated significant elevations in a majority of subjects, which requires further evaluation, characterization, and study to clarify the potential immune dysfunction by which PANS manifests and progresses.”

GiuseppaPiras, LorenzaRattazzi
Brain, Behavior, and Immunity, 29 February 2020

Patients with obsessive compulsive disorder (OCD) have increased levels of Immuno-moodulin (Imood), a protein in their lymphocytes, a type of immune cell.

Anxious mice returned to normal in a couple of days after being given an antibody that blocked Imood. Twenty-three people with OCD and twenty healthy people without OCD were tested; Imood expression was about six times higher in those with OCD. Additional research indicates the same protein, Immod, is elevated in ADHD.

Anti-lysoganglioside and other anti-neuronal autoantibodies in post-treatment Lyme Disease and Erythema Migrans after repeat infection

Brian A.Fallon, BarbaraStrobino, SeanReim, JulieStoner, Madeleine W.Cunningham Brain, Behavior, & Immunity – Health, Volume 2, February 2020, 100015. https://doi.org/10.1016/j.bbih.2019.100015

This study examines molecular mimicry targeting neural tissue after Borrelia burgdorferi (Bb) infection. Patients with Lyme disease have a greater frequency of specific anti-neuronal autoantibodies and functional neuronal activation compared to community controls without a history of Lyme disease.

“Highlights

• The EM ​+ ​prior LD group had significantly elevated anti-neuronal antibodies.
• The EM ​+ ​prior LD group had significantly elevated CaM Kinase activation.
• Anti-Lysoganglioside Antibodies are significantly elevated in the PTLS group.
• Prior infection may lead to immune priming and increased autoantibodies.”

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.

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).

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.

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.

Avis Chan and Jennifer Frankovich
Journal of Child and Adolescent Psychopharmacology-2019

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.