A critical update on the immunopathogenesis of Stiff Person Syndrome

Abstract

Background: Stiff Person Syndrome (SPS) is a relatively rare but often overlooked autoimmune neurological disorder that targets antigens within the brain's inhibitory pathways resulting in incapacitating stiffness and spasms that impact on the patients' quality of life. Although a number of immunomodulating therapies significantly improve the patients' symptoms, the exact pathogenic mechanisms remain unclear.

Materials and methods: The current literature on SPS was reviewed and combined with the authors' experience with many patients and various laboratory studies. The majority of the patients have high-titre anti-GAD (Glutamic Acid Decarboxylase) antibodies in the sera and CSF suggesting dysfunction of the GABAergic neurotransmission. These antibodies are excellent disease markers but their pathogenic role remains uncertain.

Conclusions: This review provides a critical assessment on the immunobiology of SPS, describes the identification of anti-GABARAP antibodies as a new antigenic target in the GABAergic synapse and identifies the areas for future research.