Advertisement

Neurological Sciences

, Volume 31, Issue 6, pp 871–872 | Cite as

Antibodies to aquaporin-4 in non-small cell lung cancer: a study on 50 patients

  • S. Jarius
  • A. Warth
  • K. P. Wandinger
  • P. A. Schnabel
  • H. Hoffmann
  • B. WildemannEmail author
  • T. Muley
Letter to the Editor

Dear Editor,

Neuromyelitis optica (NMO) is an aetiologically heterogeneous chronic inflammatory disorder of the CNS that predominantly affects the optic nerves and spinal cord [1]. NMO is associated with the presence of serum antibodies to aquaporin-4 (AQP4-Ab, also called NMO-IgG), the most abundant water channel in the CNS [2, 3].

Recently, De Santis et al. [4] reported on a patient with AQP4-Ab positive NMO and non-small cell lung cancer (NSCLC). Whether, NMO occurred independently in that patient or was linked to the presence of NSCLC is unknown. However, the association of AQP4-Ab and NSCLC in that case is intriguing, for AQP4 is expressed constitutively in ~40% of all NSCLC carcinomas (Warth et al., unpublished observation). AQP4-Ab may thus be produced as a part of the tumour immune response in some cases.

We were therefore interested in whether AQP4-Ab seropositive status is common among patients with NSCLC. The lack of neurological disease in the vast majority of NSCLC...

Keywords

AQP4 Expression Neuromyelitis Optica Small Cell Lung Cancer Patient Pleomorphic Carcinoma Positive Control Seron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The work of S.J. was supported by a Research Fellowship from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and by research grants from Merck Serono and Bayer Schering Pharma. The work of A.W. was supported by a grant of the Monika Kutzner-Stiftung and the PostDoc program of the Medical Faculty, University of Heidelberg. We are thankful to Brigitte Fritz, Maria Eschlbeck, and to the Nikon Imaging Center at the University of Heidelberg for excellent technical assistance.

Conflict of interest

The authors have reported that they have no conflict of interest.

References

  1. 1.
    Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG (1999) The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 53:1107–1114PubMedGoogle Scholar
  2. 2.
    Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106–2112CrossRefPubMedGoogle Scholar
  3. 3.
    Jarius S, Paul F, Franciotta D, Waters P, Zipp F, Hohlfeld R, Vincent A, Wildemann B (2008) Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica. Nat Clin Pract Neurol 4:202–214PubMedGoogle Scholar
  4. 4.
    De Santis G, Caniatti L, De Vito A, De Gennaro R, Granieri E, Tola MR (2009) A possible paraneoplastic neuromyelitis optica associated with lung cancer. Neurol Sci 30:397–400CrossRefPubMedGoogle Scholar
  5. 5.
    Jarius S, Aboul-Enein F, Waters P, Kuenz B, Hauser A, Berger T, Lang W, Reindl M, Vincent A, Kristoferitsch W (2008) Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain 131:3072–3080CrossRefPubMedGoogle Scholar
  6. 6.
    Nishiyama S, Ito T, Misu T, Takahashi T, Kikuchi A, Suzuki N, Jin K, Aoki M, Fujihara K, Itoyama Y (2009) A case of NMO seropositive for aquaporin-4 antibody more than 10 years before onset. Neurology 72:1960–1961CrossRefPubMedGoogle Scholar
  7. 7.
    Kinoshita M, Nakatsuji Y, Kimura T, Moriya M, Takata K, Okuno T, Kumanogoh A, Kajiyama K, Yoshikawa H, Sakoda S (2009) Neuromyelitis optica: passive transfer to rats by human immunoglobulin. Biochem Biophys Res Commun 386:623–627CrossRefPubMedGoogle Scholar
  8. 8.
    Bradl M, Misu T, Takahashi T, Watanabe M, Mader S, Reindl M, Adzemovic M, Bauer J, Berger T, Fujihara K, Itoyama Y, Lassmann H (2009) Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo. Ann Neurol 66:630–643CrossRefPubMedGoogle Scholar
  9. 9.
    Bennett JL, Lam C, Kalluri SR, Saikali P, Bautista K, Dupree C, Glogowska M, Case D, Antel JP, Owens GP, Gilden D, Nessler S, Stadelmann C, Hemmer B (2009) Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica. Ann Neurol 66:617–629CrossRefPubMedGoogle Scholar
  10. 10.
    Graus F, Dalmou J, Rene R, Tora M, Malats N, Verschuuren JJ, Cardenal F, Vinolas N, Garcia del Muro J, Vadell C, Mason WP, Rosell R, Posner JB, Real FX (1997) Anti-Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival. J Clin Oncol 15:2866–2872PubMedGoogle Scholar
  11. 11.
    Jarius S, Probst C, Borowski K, Franciotta D, Wildemann B, Stoecker W, Wandinger KP (2010) Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J Neurol Sci 291:52–56Google Scholar
  12. 12.
    Nicchia GP, Mastrototaro M, Rossi A, Pisani F, Tortorella C, Ruggieri M, Lia A, Trojano M, Frigeri A, Svelto M (2009) Aquaporin-4 orthogonal arrays of particles are the target for neuromyelitis optica autoantibodies. Glia 57:1363–1373CrossRefPubMedGoogle Scholar
  13. 13.
    Pittock SJ, Lennon VA (2008) Aquaporin-4 autoantibodies in a paraneoplastic context. Arch Neurol 65:629–632CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • S. Jarius
    • 1
  • A. Warth
    • 2
  • K. P. Wandinger
    • 3
    • 4
  • P. A. Schnabel
    • 2
  • H. Hoffmann
    • 5
  • B. Wildemann
    • 1
    Email author
  • T. Muley
    • 6
  1. 1.Division of Molecular Neuroimmunology, Department of NeurologyUniversity of HeidelbergHeidelbergGermany
  2. 2.Institute of PathologyUniversity of HeidelbergHeidelbergGermany
  3. 3.Institute for Experimental Immunology Affiliated to EuroimmunLuebeckGermany
  4. 4.Institute for Neuroimmunology and Clinical MS Research, Center for Molecular Neurobiology Hamburg (ZMNH)University Medical Center EppendorfHamburgGermany
  5. 5.Translational Research UnitThoraxklinik HeidelbergHeidelbergGermany
  6. 6.Department of Thoracic SurgeryThoraxklinik HeidelbergHeidelbergGermany

Personalised recommendations