Neurology

Anti–AK5 Antibodies

Test details

This laboratory assay detects IgG autoantibodies against adenylate kinase 5 (AK5), an intracellular enzyme expressed in the central nervous system that plays an important role in cellular energy homeostasis. Anti-AK5 antibodies are specific biomarkers of a rare form of autoimmune limbic encephalitis, typically characterised by subacute amnesia, psychiatric symptoms and, less frequently, seizures. The condition is usually non-paraneoplastic and occurs predominantly in older males. The presence of anti-AK5 antibodies suggests a cytotoxic T-cell–mediated pathogenesis, with neuronal injury and a limited response to conventional immunosuppressive therapies. Clinical workup often shows typical MRI findings (mesial temporal T2/FLAIR hyperintensities) and severe cognitive deficits that may persist despite treatment.

 

This test supports the differential diagnosis, helping to distinguish anti-AK5 encephalitis from more common autoimmune encephalitis (e.g., anti-LGI1). It is recommended in patients with a rapidly progressive limbic encephalitis phenotype, especially when no neoplasm is found and immunotherapy response is poor. Diagnosis is supported by detection of anti-AK5 in serum and/or cerebrospinal fluid (CSF). As CSF provides higher sensitivity than serum, testing both sample types is recommended.

Sample type

Serum, plasma, CSF

Method

IFA cells

Preparation

Fasting for at least 8-12 hours before sampling

Storage conditions

Refer to the Health Service Charter to check storage conditions

Shipping

+2/+8°C

References

McKeon-Makki I, McKeon A, Yang B, Pittock SJ, Lopez-Chiriboga S, Komorowski L, Miske R, Zekeridou A. Adenylate kinase 5 (AK5) autoimmune encephalitis: Clinical presentations and outcomes in three new patients. J Neuroimmunol. 2022 Jun 15;367:577861. doi: 10.1016/j.jneuroim.2022.577861. Epub 2022 Apr 4. PMID: 35405429; PMCID: PMC9186138.

 

Muñiz-Castrillo S, Hedou JJ, Ambati A, Jones D, Vogrig A, Pinto AL, Benaiteau M, de Broucker T, Fechtenbaum L, Labauge P, Murnane M, Nocon C, Taifas I, Vialatte de Pémille C, Psimaras D, Joubert B, Dubois V, Wucher V, Desestret V, Mignot E, Honnorat J. Distinctive clinical presentation and pathogenic specificities of anti-AK5 encephalitis. Brain. 2021 Oct 22;144(9):2709-2721. doi: 10.1093/brain/awab153. PMID: 33843981; PMCID: PMC8557339.

 

Bien CI, Nehls F, Kollmar R, Weis M, Steinke W, Woermann F, Dalmau J, Bien CG. Identification of adenylate kinase 5 antibodies during routine diagnostics in a tissue-based assay: Three new cases and a review of the literature. J Neuroimmunol. 2019 Sep 15;334:576975. doi: 10.1016/j.jneuroim.2019.576975. Epub 2019 May 29. PMID: 31177032.

 

Ng AS, Kramer J, Centurion A, Dalmau J, Huang E, Cotter JA, Geschwind MD. Clinico-pathological correlation in adenylate kinase 5 autoimmune limbic encephalitis. J Neuroimmunol. 2015 Oct 15;287:31-5. doi: 10.1016/j.jneuroim.2015.08.009. Epub 2015 Aug 8. PMID: 26439959; PMCID: PMC4879958.

 

Tüzün E, Rossi JE, Karner SF, Centurion AF, Dalmau J. Adenylate kinase 5 autoimmunity in treatment refractory limbic encephalitis. J Neuroimmunol. 2007 May;186(1-2):177-80. doi: 10.1016/j.jneuroim.2007.03.015. Epub 2007 Apr 25. PMID: 17462746; PMCID: PMC2040128.

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