Significance of Neuronal Autoantibodies in Comparison to Infectious Etiologies among Patients Presenting with Encephalitis in a Region with a High Prevalence of Infections

Abstract

Background: Prevalence of antibody-mediated autoimmune encephalitis (AE) is reported to be comparable to infectious encephalitis in Western populations. We evaluated the frequency and significance of AE and neuronal autoantibodies in comparison to infectious etiologies among patients presenting with encephalitis in a South Asian population.

Methods: Ninety-nine consecutive patients with a clinical diagnosis of encephalitis/meningoencephalitis admitted to two of the largest tertiary-care hospitals in Sri Lanka were studied. PCR and ELISA were used to screen viruses while Gram stain and culture were used to screen bacteria. Sera were tested for antibodies binding to primary embryonic rat hippocampal neuronal cultures and cell-based assays for antibodies to NMDAR, LGI1, CASPR2, Contactin2, AMPAR, GABA_AR, GABA_BR, aquaporin-4 and MOG.

Results: Patient ages ranged from 1 month to 73 years (mean = 24.91; SD = 21.33) with a male: female ratio of 1.75:1. A viral etiology was identified in 27.3% and bacterial meningoencephalitis was diagnosed in 17.1%. Sera of nine patients had antibodies binding to live primary neurons, but only five had specific antibodies to CASPR2 (n = 1), NMDAR (n = 2) or GABA_BR-antibodies (n = 2). Moreover, the patients with CASPR2 antibodies and NMDAR-antibodies were also positive for dengue antibodies. Only the two patients with NMDAR-antibodies had features and responses to immunotherapy consistent with AE.

Conclusions: Identified infectious forms of meningoencephalitis (44.4%) greatly exceeded the occurrence of neuronal autoantibodies (9.1%) and AE (2%) in Sri Lanka, and this may be common in those regions where infections are prevalent.

Keywords: Autoimmune encephalitis; NMDAR; Sri Lanka; meningoencephalitis.

Figure 1

(a) Primary embryonic rat hippocampal neurons in culture labelled with MAP2 (neuronal stain) and DAPI (nuclear stain). Patient serum antibodies are detected binding to the surface of neuronal cell bodies and processes (top row). In contrast, healthy control serum does not show any binding in the neuronal cultures (bottom row). Scale bar = 10 mm. (b) Representative immunofluorescence images of a cell-based assay. HEK cells transiently transfected with NR1 and labelled with DAPI (nuclear stain) shows cell surface binding with patient serum (top row). Healthy control serum does not show any binding (bottom row). Scale bar = 10 mm