ANTI -NMDA RECEPTOR ENCEPHALITIS: A POSSIBLE APPROACH TO DEVELOP A COST-EFFECTIVE TEST FOR ANTI NMDA RECEPTOR ANTIBODY DETECTION

Authors

  • Shafain Sheikh Shifa International Hospital
  • Tahir Aziz Ahmed Department of Immunology, Shifa International Hospital, Islamabad-Pakistan
  • Arsalan Ahmad Department of Neurology, Shifa International Hospital, Islamabad-Pakistan

DOI:

https://doi.org/10.55519/JAMC-02-11655

Keywords:

rodent brain, Indirect Immunofluorescence, cell based assays, cost effective

Abstract

Background: Autoimmune encephalitis (AIE) has been ranked as the third most common cause of encephalitis after viral encephalitis and acute disseminated encephalomyelitis. The estimated incidence is 5–8 cases per 100,000 population. The objective of this study was to develop a cost-effective test for detection of anti NMDA R antibodies by using in house prepared rodent brain tissue sections which could facilitate timely diagnosis and management of anti NMDA R Encephalitis, which if left undiagnosed may prove fatal. Methods: A total of 500 samples sent for autoimmune encephalitis related antibody testing were included in this cross-sectional study from April 2019 to March 2021 at department of Immunology, Shifa International Hospital (SIH), Islamabad. Rodent brain was dissected to prepare tissue sections on which samples were tested by Indirect Immunofluorescence. Simultaneously samples were tested on cell-based assay (CBA) which is gold standard for testing anti NMDA R antibodies. Sensitivity, specificity, positive and negative predictive values were calculated. Results: Median age of patients who tested positive for anti NMDA encephalitis was 19 years (range: 1 to 57). Out these 76% were female and 24% males. 5% patients tested positive for anti NMDA antibodies out of those suspected to be suffering from autoimmune encephalitis. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of rodent brain IF for anti-NMDR antibodies taking CBA as gold standard was 92.6%, 98.5%, 78.1% and 99.6% respectively. The accuracy of the procedure was 98.2%. Conclusion: Indirect immunofluorescence (IF) on rodent brain tissue sections can be useful as a cost-effective alternate for resource constrained laboratories for timely detection of anti NMDA R antibodies facilitating timely diagnosis and management of anti-NMDA receptor encephalitis patients.

References

Wickramasinghe N, Dasanayake D, Malavige N, de Silva R, Chang T. Autoimmune encephalitis in a South Asian population. BMC Neurol 2021;21(1):1–8.

Lin K, Lin J. Neurocritical care for Anti-NMDA receptor encephalitis. Biomed J 2020;43(3):251–8.

Huang YQ, Xiong H. Anti-NMDA receptor encephalitis: a review of mechanistic studies. Int J Physiol Pathophysiol Pharmacol 2021;13(1):1–11.

Goodfellow J, Mackay G. Autoimmune Encephalitis. J R Coll Physicians Edinb 2019;49(4):287–94.

Xu X, Lu Q, Huang Y, Fan S, Zhou L, Yuan J, et al. Anti-NMDAR encephalitis: A single-center, longitudinal study in China. Neurol Neuroimmunol Neuroinflamm 2019;7(1):e633.

Wang W, Zhang L, Chi X, He L, Zhou D, Li J. Psychiatric Symptoms of Patients With Anti-NMDA Receptor Encephalitis. Front Neurol 2020;10:1330.

Dalmau J, Armangué T, Planagumà J, Radosevic M, Mannara F, Leypoldt F, et al. An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models. Lancet Neurol 2019;18(11):1045–57.

Abboud H, Probasco J, Irani S, Ances B, Benavides D, Bradshaw M, et al. Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry 2021;92(7):757–68.

Li J, Wang Q, Wang H. Autoantibodies detection in anti-N-methyl-D-aspartate receptor encephalitis. Ann Transl Med 2023;11(7):284.

Ellul M, Solomon T. Acute encephalitis – diagnosis and management. Clin Med 2018;18(2):155–9.

Samanta D, Lui F. Anti-NMDA Receptor Encephalitis [Internet]. Ncbi.nlm.nih.gov. 2022 [cited 2022 9 Oct]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551672/

Lim J, Lee S, Jung K, Kim S, Shin J, Moon J, et al. Anti-N-Methyl-D-Aspartate Receptor Encephalitis in Korea: Clinical Features, Treatment, and Outcome. J Clin Neurol 2014;10(2):157–61.

Kong S, Chen Y, Su I, Lin J, Chou I, Chou M, et al. Immunotherapy for anti-NMDA receptor encephalitis: Experience from a single center in Taiwan. Pediatr Neonatol 2019;60(4):417–22.

Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: An observational cohort study. Lancet Neurol 2013;12(2):157–65.

Bost C, Pascual O, Honnorat J. Autoimmune encephalitis in psychiatric institutions: current perspectives. Neuropsychiatr Dis Treat 2016;12:2775–87.

Wang W, Li JM, Hu FY, Wang R, Hong Z, He L, et al. Anti‐NMDA receptor encephalitis: clinical characteristics, predictors of outcome and the knowledge gap in southwest China. Eur J Neurol 2016;23(3):621–9.

Zhong R, Chen Q, Zhang X, Zhang H, Lin W. Risk Factors for Mortality in Anti-NMDAR, Anti-LGI1, and Anti-GABABR Encephalitis. Front Immunol 2022;13:845365.

Deng Q, Liu Y, Mao Z, Chen Y, Ping Y, Zhu G, et al. The antibody assay in suspected autoimmune encephalitis from positive rate to test strategies. Front Immunol 2022;13:803854.

Ricken G, Schwaiger C, De Simoni D, Pichler V, Lang J, Glatter S, et al. Detection methods for autoantibodies in suspected autoimmune encephalitis. Front Neurol 2018;9:841.

Downloads

Published

2024-06-30