Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
권호 표지
DOI QR코드

DOI QR Code

Clinical Usefulness of Cell-based Indirect Immunofluorescence Assay for the Detection of Aquaporin-4 Antibodies in Neuromyelitis Optica Spectrum Disorder

  • Kang, Eun-Suk (Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Min, Ju-Hong (Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Kwang Ho (Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Byoung Joon (Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Published : 2012.09.01
⟨ Previous Next ⟩

Abstract

Background: The presence of antibodies to aquaporin-4 (AQP4) has been identified as a key characteristic of neuromyelitis optica spectrum disorder (NMOSD), an autoimmune inflammatory demyelinating central nervous system (CNS) disorder. We evaluated the performance of a cell-based indirect immunofluorescence assay (CIIFA) for detecting AQP4 antibodies using antigen prepared with a recombinant AQP4 peptide transfection technique and assessed the usefulness of CIIFA for diagnosis of NMOSD in routine clinical practice. Methods: Forty-six serum samples from 36 patients as a comparison set and another 101 patients enrolled consecutively from a neurology clinic were included. CIIFA and fluorescence immunoprecipitation assays (FIPA) were performed. CIIFA was performed at 2 different institutions for comparison purposes. Results: CIIFA and FIPA sensitivity in the comparison set was 86% and 79% in neuromyelitis optica (NMO) patients and 55% and 36% in high-risk NMO patients, respectively. The semiquantitative titer measured by CIIFA correlated well with the arbitrary unit (fluorescence units [FU]) derived from FIPA (r=0.66). Titers measured by CIIFA and FIPA were elevated in NMO patients compared to high-risk NMO patients (1:240 vs. 1:180 and 8,390 vs. 4,059 FU, respectively). The frequency of AQP4 antibody detection by CIIFA in 101 consecutively enrolled patients was 100% in NMO and 23% in high-risk NMO patients, while only 4.6% in control patients, including those with multiple sclerosis. Conclusions: Detection of AQP4 antibodies by CIIFA provides sensitive and highly specific diagnostic information for NMO and high-risk NMO patients, which can be used to differentiate these conditions from other demyelinating CNS diseases.

Keywords

References

  1. Devic E. Subacute myelitis complicated by optic neuritis. Bull Med 1894;8:1033-4.
  2. Wingerchuk DM, Hogancamp WF, O'Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic's syndrome). Neurology 1999;53:1107-14. https://doi.org/10.1212/WNL.53.5.1107
  3. de Seze J, Stojkovic T, Ferriby D, Gauvrit JY, Montagne C, Mounier-Vehier F, et al. Devic's neuromyelitis optica: clinical, laboratory, MRI and outcome profile. J Neurol Sci 2002;197:57-61. https://doi.org/10.1016/S0022-510X(02)00043-6
  4. Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol 2007;6:805-15. https://doi.org/10.1016/S1474-4422(07)70216-8
  5. Kira J. Multiple sclerosis in the Japanese population. Lancet Neurol 2003;2:117-27. https://doi.org/10.1016/S1474-4422(03)00308-9
  6. Matsushita T, Isobe N, Matsuoka T, Shi N, Kawano Y, Wu XM, et al. Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibodynegative opticospinal multiple sclerosis in Japanese. Mult Scler 2009;15:834-47. https://doi.org/10.1177/1352458509104595
  7. Lennon V, Wingerchuk D, Kryzer T, Pittock S, Lucchinetti C, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364:2106-12. https://doi.org/10.1016/S0140-6736(04)17551-X
  8. Lennon VA. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005;202:473-7. https://doi.org/10.1084/jem.20050304
  9. Hiroaki Y, Tani K, Kamegawa A, Gyobu N, Nishikawa K, Suzuki H, et al. Implications of the aquaporin-4 structure on array formation and cell adhesion. J Mol Biol 2006;355:628-39. https://doi.org/10.1016/j.jmb.2005.10.081
  10. Paul F, Jarius S, Aktas O, Bluthner M, Bauer O, Appelhans H, et al. Antibody to aquaporin 4 in the diagnosis of neuromyelitis optica. PLoS Med 2007;4:e133. https://doi.org/10.1371/journal.pmed.0040133
  11. Papeix C, Vidal JS, de Seze J, Pierrot-Deseilligny C, Tourbah A, Stankoff B, et al. Immunosuppressive therapy is more effective than interferon in neuromyelitis optica. Mult Scler 2007;13:256-9. https://doi.org/10.1177/1352458506070732
  12. Cree BA, Lamb S, Morgan K, Chen A, Waubant E, Genain C. An open label study of the effects of rituximab in neuromyelitis optica. Neurology 2005;64:1270-2. https://doi.org/10.1212/01.WNL.0000159399.81861.D5
  13. Keegan M, Pineda AA, McClelland RL, Darby CH, Rodriguez M, Weinshenker BG. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 2002;58:143-6. https://doi.org/10.1212/WNL.58.1.143
  14. Jarius S and Wildemann B. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat Rev Neurol 2010;6:383-92. https://doi.org/10.1038/nrneurol.2010.72
  15. Waters P and Vincent A. Detection of anti-aquaporin-4 antibodies in neuromyelitis optica: current status of the assays. Int MS J 2008;15:99-105.
  16. Jarius S, Probst C, Borowski K, Franciotta D, Wildemann B, Stoecker W, et al. Standardized methods for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J Neurol Sci 2010;291:52-6. https://doi.org/10.1016/j.jns.2010.01.002
  17. Hayakawa S, Mori M, Okuta A, Kamegawa A, Fujiyoshi Y, Yoshiyama Y, et al. Neuromyelitis optica and anti-aquaporin-4 antibodies measured by an enzyme-linked immunosorbent assay. J Neuroimmunol 2008;196:181-7. https://doi.org/10.1016/j.jneuroim.2008.03.009
  18. Takahashi T, Fujihara K, Nakashima I, Misu T, Miyazawa I, Nakamura M, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 2007;130:1235-43. https://doi.org/10.1093/brain/awm062
  19. Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006;66:1485-9. https://doi.org/10.1212/01.wnl.0000216139.44259.74
  20. Waters P, Jarius S, Littleton E, Leite MI, Jacob S, Gray B, et al. Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neurol 2008;65:913-9. https://doi.org/10.1001/archneur.65.7.913
  21. Lucchinetti CF, Mandler RN, McGavern D, Bruck W, Gleich G, Ransohoff RM, et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain 2002;125:1450-61. https://doi.org/10.1093/brain/awf151
  22. Takahashi T, Fujihara K, Nakashima I, Misu T, Miyazawa I, Nakamura M, et al. Establishment of a new sensitive assay for anti-human aquaporin-4 antibody in neuromyelitis optica. Tohoku J Exp Med 2006;210:307-13. https://doi.org/10.1620/tjem.210.307
  23. Fazio R, Malosio M, Lampasona V, De Feo D, Privitera D, Marnetto F, et al. Antiacquaporin 4 antibodies detection by different techniques in neuromyelitis optica patients. Mult Scler 2009;15:1153-63. https://doi.org/10.1177/1352458509106851
  24. De Vidi I, Boursier G, Delouche N, Portales P, Cadars E, Bouthier M, et al. Strategy for anti-aquaporin-4 auto-antibody identification and quantification using a new cell-based assay. Clin Immunol 2011;138:239-46. https://doi.org/10.1016/j.clim.2010.11.012
  25. Hinson SR, McKeon A, Fryer JP, Apiwattanakul M, Lennon VA, Pittock SJ. Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4-expressing cells. Arch Neurol 2009;66:1164-7. https://doi.org/10.1001/archneurol.2009.188
  26. McKeon A, Fryer JP, Apiwattanakul M, Lennon VA, Hinson SR, Kryzer TJ, et al. Diagnosis of neuromyelitis spectrum disorders: comparative sensitivities and specificities of immunohistochemical and immunoprecipitation assays. Arch Neurol 2009;66:1134-8. https://doi.org/10.1001/archneurol.2009.178
  27. Pittock SJ, Lennon VA, de Seze J, Vermersch P, Homburger HA, Wingerchuk DM, et al. Neuromyelitis optica and non organ-specific autoimmunity. Arch Neurol 2008;65:78-83. https://doi.org/10.1001/archneurol.2007.17
  28. Jarius S, Jacobi C, de Seze J, Zephir H, Paul F, Franciotta D, et al. Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders. Mult Scler 2011;17:1067-73. https://doi.org/10.1177/1352458511403958
  29. Hinson SR, McKeon A, Lennon VA. Neurological autoimmunity targeting aquaporin-4. Neuroscience 2010;168:1009-18. https://doi.org/10.1016/j.neuroscience.2009.08.032
  30. Min JH, Kim HJ, Kim BJ, Lee KW, Sunwoo IN, Kim SM, et al. Brain abnormalities in Sjogren syndrome with recurrent CNS manifestations: association with neuromyelitis optica. Mult Scler 2009;15:1069-76. https://doi.org/10.1177/1352458509106228
  31. Jarius S, Aboul-Enein F, Waters P, Kuenz B, Hauser A, Berger T, et al. Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain 2008;131:3072-80. https://doi.org/10.1093/brain/awn240

Cited by

  1. Aquaporin‐4 Antibodies (NMO‐IgG) as a Serological Marker of Neuromyelitis Optica: A Critical Review of the Literature vol.23, pp.6, 2013, https://doi.org/10.1111/bpa.12084
  2. The usefulness of brain MRI at onset in the differentiation of multiple sclerosis and seropositive neuromyelitis optica spectrum disorders vol.20, pp.6, 2012, https://doi.org/10.1177/1352458513506953
  3. Low Levels of Vitamin D in Neuromyelitis Optica Spectrum Disorder: Association with Disease Disability vol.9, pp.9, 2012, https://doi.org/10.1371/journal.pone.0107274
  4. The neuromyelitis optica presentation and the aquaporin-4 antibody in HIV-seropositive and seronegative patients in KwaZulu-Natal, South Africa vol.18, pp.1, 2017, https://doi.org/10.4102/sajhivmed.v18i1.684
  5. Initial Pattern of Optic Nerve Enhancement in Korean Patients with Unilateral Optic Neuritis vol.31, pp.1, 2012, https://doi.org/10.3341/kjo.2017.31.1.71
  6. Fatigue in patients with neuromyelitis optica spectrum disorder and its impact on quality of life vol.12, pp.5, 2017, https://doi.org/10.1371/journal.pone.0177230
  7. Clinical characteristics of late-onset neuromyelitis optica spectrum disorder: A multicenter retrospective study in Korea vol.23, pp.13, 2017, https://doi.org/10.1177/1352458516685416
  8. The IL-10-producing regulatory B cells (B10 cells) and regulatory T cell subsets in neuromyelitis optica spectrum disorder vol.39, pp.3, 2012, https://doi.org/10.1007/s10072-018-3248-y
  9. Association of Optic Neuritis with Neuromyelitis Optica Spectrum Disorder and Multiple Sclerosis in Korea vol.33, pp.1, 2012, https://doi.org/10.3341/kjo.2018.0050
  10. Higher Disease and Pain Severity and Fatigue and Lower Balance Skills Are Associated with Higher Prevalence of Falling among Individuals with the Inflammatory Disease of Neuromyelitis Optica Spectrum vol.9, pp.11, 2012, https://doi.org/10.3390/jcm9113604
  11. Stress cardiomyopathy associated with area postrema syndrome as a presentation of neuromyelitis optica: case report vol.20, pp.1, 2012, https://doi.org/10.1186/s12883-020-01784-3