Folate Receptor Alpha Autoantibodies in the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Population

Lindsey Wells; Nancy O'Hara; Richard E Frye; Neeshi Hullavard; Erica Smith

doi:10.3390/jpm14020166

Folate Receptor Alpha Autoantibodies in the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Population

J Pers Med. 2024 Jan 31;14(2):166. doi: 10.3390/jpm14020166.

Authors

Lindsey Wells¹, Nancy O'Hara², Richard E Frye³, Neeshi Hullavard⁴, Erica Smith⁵

Affiliations

¹ Lindsey Wells ND LLC, Wilton, CT 06897, USA.
² Nancy O'Hara and Associates LLC, Wilton, CT 06897, USA.
³ Autism Discovery and Treatment Foundation, Phoenix, AZ 85050, USA.
⁴ Massachusetts General Hospital, Boston, MA 02114, USA.
⁵ Natural Pediatrics of CT, Stamford, CT 06905, USA.

Abstract

The folate receptor alpha autoantibodies (FRAAs) are associated with cerebral folate deficiency (CFD) and autism spectrum disorder (ASD). Both of these syndromes have overlapping characteristics with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). Thus, we propose that the FRAAs may contribute to the symptomatology of PANS/PANDAS. To test this hypothesis, 1 mL of serum from 47 patients (age range = 6-18 years old) clinically diagnosed with PANS/PANDAS was sent to Vascular Strategies (Plymouth Meeting, PA, USA) for analysis of FRAAs. Moreover, 63.8% of PANS/PANDAS patients (male = 15; female = 15) were found to have either the blocking and/or blinding FRAAs, with 25 (83.3%; male = 14; female = 11) having binding FRAAs, two (6.7%; all female = 2) having blocking FRAAs, and 3 (10%; male = 1; female = 2) having both binding and blocking. Furthermore, surprisingly, ASD was associated with a 0.76 lower binding titer (p = 0.02), and severe tics were associated with a 0.90 higher binding titer (p = 0.01). A case of a FRAA-positive patient is provided to illustrate that a treatment plan including leucovorin can result in symptom improvement in patients with PANS/PANDAS who are FRAA-positive. These data, for the first time, demonstrate that PANS/PANDAS is associated with FRAAs and suggest folate metabolism abnormalities may contribute to PANS/PANDAS symptomatology. Further studies investigating the therapeutic nature of leucovorin in the treatment of PANS/PANDAS are needed. Such studies may open up an alternative, safe, and well-tolerated treatment for those with the PANS/PANDAS diagnosis.

Keywords: OCD; PANDAS; PANS; autism spectrum disorder; folate receptor alpha antibodies; leucovorin; tics.

Grants and funding

Religen, Inc. (Plymouth Meeting, PA, USA) supported the cost of publishing this article but had no role in the design of the study, in the collection, analysis, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.