Beyond paraneoplastic neurological syndromes: Anti-neuronal antibodies in neuropsychiatric systemic lupus erythematosus

Abstract

Introduction

Anti-neuronal antibodies target antigens produced by tumour cells and cells of nervous system. These antibodies are formed as a result of autoimmune response elicited by the underlying malignancy, when proteins restricted to immune privileged neurons are presented by the tumour. Previous studies have shown presence of anti-neuronal antibodies in systemic lupus erythematosus and neuropsychiatric lupus (NPSLE) but information on individual antibodies and their pathogenic role is lacking.

Aims/Objective

To assess the frequency of anti-neuronal antibodies in our neuropsychiatric lupus cohort and to assess any significant association with specific neurological syndrome and to see if the antibodies were more likely to occur in active rather than inactive neuropsychiatric lupus.

Methodology

This cross-sectional study was conducted in our center from 2019 to 2022. Neuropsychiatric manifestations were defined according to 1999 American College of Rheumatology (ACR) nomenclature and case definitions for neuropsychiatric lupus. Samples were taken from active or inactive NPSLE patients with their informed consent. Testing was done on an anti-neuronal antigen panel which consisted of [Amphiphysin, CV2, GAD 65, PNMA2 (Ma-2/Ta), Ri, Yo, Hu, recoverin, SOX1, titin, Zic, Tr)] by semi-quantitative Line immune assay. Association between the categorical variables and antibody positivity group was established using chi-square/Fisher’s exact test as appropriate.

Results

65 patients were recruited, of which 23 (35%) patients had active NPSLE at the time of sample collection. Anti-neuronal antibodies were positive in 13/65 (20%) patients with anti-Gad 65 antibodies having the highest frequency (6.2%) followed by anti CV 2 (3.1%), anti Sox1 (3.1%), anti Amphiphysin (3.1%) anti recoverin (1.5%), anti Yo (1.5%) and anti Zic (1.5%). The panel of anti-neuronal antibodies did not show any specific association with NPSLE features.

However, an interesting finding was that, patients with active disease had higher odds of having anti-neuronal antibodies with an OR = 10 (95% CI:2.38 -42) (p < 0.001) than inactive disease.

Conclusion

Anti-neuronal antibodies were more likely to be positive in active neuropsychiatric lupus patients, and these antibodies which are commonly used to diagnose paraneoplastic syndromes may have a potential role in the diagnosis of NPSLE.