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PANDAS Plus Autism: Treatment with IVIg

David S Younger

David S Younger, Global Institute of Public Health, New York University, New York, USA

Correspondence to: David S Younger, MD, MPH, Global Institute of Public Health, New York University, New York NY 10010, 333 East 34th Street, New York NY 10016, USA.
Email: youngd01@nyu.edu
Telephone: +1-212-213-3778
Fax: +1-212-213-3779
Received: August 5, 2015
Revised: September 1, 2015
Accepted: September 5, 2015
Published online: March 3, 2016

ABSTRACT

Poly(Q) disorders includes neurodegenerative disorders associated with irreversible loss of specific neurons in adult brain. The causative factor has been identified as the abnormal expansion of CAG repeats in protein coding region of the gene which leads to formation of protein Inclusion Bodies (IBs) and altered cellular physiology. The molecular pathogenesis of poly(Q) disease involves protein mis-folding, aggregate formation, blockage of axonal transport, mitochondrial dysfunction and global transcriptional dysregulation. Formation of inclusion bodies is a hallmark and common characteristic feature of all poly(Q) disorders. In view of limitation attached with human genetics, Drosophila has emerged as an excellent system to model the human neurodegenerative disorders due to availability of flexible yet powerful genetic tools and owing to the similarity between some of the fundamental cellular processes with humans. Drosophila system has been extensively utilized not only to decipher the mechanistic detail of diseases pathogenesis but also to screen several genetic and chemical modifiers which could potentially help in designing novel therapeutic strategies. The Drosophila melanogaster, thus, expected to contribute meaningfully towards novel discoveries to design novel therapeutic strategies to combat the devastating human neurodegenerative disorders.

© 2016 ACT. All rights reserved.

Key words: Pandas; Autism; IVIg

Singh MD, Chanu SI, Sarkar S. Deciphering the Enigma of Human Poly(Q) Disorders: Contribution of Drosophila melanogaster. International Journal of Neurology Research 2016; 2(1): 216-223 Available from: URL: http://www.ghrnet.org/index.php/jnr/article/view/1468

Introduction

Younger DS. PANDAS Plus Autism: Treatment with IVIg. International Journal of Neurology Research 2016; 1(2): 224-225 Available from: URL: http://www.ghrnet.org/index.php/ijnr/article/view/1468

EDITORIAL

Bouboulis and Mast[1] note sustained benefit of anti-infective therapy followed by intravenous immune globulin (IVIg) when the latter is administered for several months to a year or morein their review of a cohort of six patients with PANDAS and humoral immunodeficiency, including two children with autism.Despite past controversy in the epidemiologic rigor surrounding PANDAS, there has been progress in the understanding of this post-infectious autoimmune disorder that led up to the present therapeutic approach employing immune modulatory therapy. Early serologic investigations[2-4] suggested a causal relation of Group A β-hemolytic streptococcus (GABHS) infection to PANDAS,however it was a fortuitous leap of faith that the insult would be immune-mediated similar to Sydenham chorea(SC). Anti-streptolysin (ASO) antibodies distinguished cases of PANDAS versus non-cases providing evidence of antecedent streptococcal infection with higher sustained titers and slower rates of decline in the antibody rise due to the more potent immune response that was noted to be associated with repeated GABHS infection.

In other studies[5-8] a T-cell alloantigen identified by monoclonal antibodies as D8/D17 attached to the surface of B-cells as a susceptibility factor for rheumatic fever was found in 85% of patients with PANDAS and in 89% of those with SC, but in only 17% of controls. Although not so shown in PANDAS, the GNcNAc epitope expressed in SC monoclonal antibodies (mAb)was capable of provoking a strong humoral response during active streptococcal infection and in post-infectious sequeladue to terminal O-linked GLcNAc residues bearing structural similarity to many host glycoconjugates. Experimental animals immunized with GlcNAc mAb led to T-cell dependent antibody responses and persistently high titers to streptococcal carbohydrate. Moreover, lysoganglioside GM1-specific antibodies present in the cerebrospinal fluid of patients with active disease blocked SC mAb in acute sera that otherwise bound to human caudate-putamen tissue. Active but not convalescent PANDA serum IgG reacts with GlcNAc epitope of the streptococcal GAC and lysoganglioside GM1 as in SC in a manner that suggests a role for aberrant cell signaling in the immunopathogenesis of PANDAS.

The clinical benefits in neuropsychiatric symptoms so noted in up to 58% of children with IVIg that lasted for up to one year[9] incentivized the same Investigators to test the efficacy in a double-blind placebo-controlled study using primary and secondary outcome measures (ClinicalTrials.gov Identifier NCT01281969), and to include children with autism spectrum disorder (ASD) and related psychiatric, developmental, and behavioral problems with the goal of assessing the role of future treatments possibly including IVIg (ClinicalTrials.gov Identifier NCT01778504). The report of Bouboulis and Mast[1] not only supports the need for future double-blind placebo-controlled trials to examine the continuing impact of IVIg on PANDAS, but cautions the medical community as to the selection of potentially treatable children with ASD, namely those with underlying immune deficiency that places them at higher risk for PANDAS.

CONFLICT OF INTERESTS

The author has no conflicts of interest to declare.

REFERENCES

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9 Snider LA, Swedo SE. PANDAS: current status and directions for research. Molecular Psychiatry 2004; 9: 900-907.

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