Specificity of NMO Marker Confirmed


Is neuromyelitis optica (nmo) igg autoantibody unique to NMO or is it expressed in multiple sclerosis (MS) as well? Recent studies have confirmed the autoantibody’s specificity and are shedding more light on how NMO IgG's autoantigen, the water channel aquaporin-4 (AQP4), uniquely behaves in NMO and MS.

IS NEUROMYELITIS OPTICA (NMO) IGG AUTOANTIBODYunique to NMO or is it expressed in multiple sclerosis(MS) as well? Recent studies have confirmed theautoantibody's specificity and are shedding morelight on how NMO IgG's autoantigen, the waterchannel aquaporin-4 (AQP4), uniquely behaves inNMO and MS.

To decipher whether NMO IgG autoantibody expressionis an effect of CNS inflammation andtherefore also present in opticospinal phenotypes ofMS as well as relapsing-remitting MS (RRMS), ateam of neurologists from Stanford University andthe University of California at San Francisco studiedserum NMO IgG autoantibody levels in 130 patientswith RRMS. None of the patients tested positivefor the NMO IgG autoantibody, leading theinvestigators to conclude that NMO IgG is a keymarker that differentiates NMO from MS.

Similar findings were published in the March 27,2007, issue of Neurology. This study evaluated thepresence of NMO IgG autoantibody in the sera of36 patients with NMO, 80 patients with MS, and 5patients with longitudinally extensive transversemyelitis (LETM). The serum of 22 (61%) patientswith NMO and of 4 (80%) patients with LETM testedpositive for NMO IgG. The serum of only 1 patientwith MS was NMO IgG autoantibody-positive.

The study is the first published confirmation ofthe work of a team led by Vanda Lennon, MD, professorof immunology and neurology at the MayoClinic in Rochester, Minnesota.

Vanda and colleagues also showed that NMOIgG selectively binds to AQP4, suggesting thatAQP4 may be implicated NMO pathogenesis-ahighly novel finding because it marks the first timean autoantigen has been linked with a demyelinatingdisorder. In an article published in The Journal ofExperimental Medicine in 2005, the team describedhow AQP4 was specifically concentrated in sites ofspinal cord inflammation in persons with NMO andpostulated that this was either a unique autoimmunereaction or related to an IgG-mediated dysfunctionof the water channel homeostat.

Another study, published in the February 2007issue of Acta Neuropathologica further showed howthe expression of AQP4 differs in patients withNMO and MS. In this study, researchers looked atAQP4 expression in disease-free brain tissue and inbrain tissue samples from 7 donors with active orinactive MS and from 1 donor with NMO. AQP4was expressed in all active MS lesions, a few of theinactive lesions, no NMO lesions, and a few disease-free white matter samples. The findings suggesta different mechanism of pathogenesis andprogression between the 2 related disease states.

For further information see:

  • Smith C, Waubant E, Langer-Gould A. Prevalenceof neuromyelitis optica (NMO) IgG antibody in anactive relapsing-remitting multiple sclerosis population(RRMS). Neurology. 2007;68(suppl 1):A16.
  • Jarius S, Franciotta D, Bergamaschi R, et al. NMOIgGin the diagnosis of neuromyelitis optica. Neurology. 2007;68:1076-1077.
  • Lennon VA, Wingerchuk DM, Kryzer TJ, et al. Aserum autoantibody marker of neuromyelitis optica:distinction from multiple sclerosis. Lancet. 2004;364:2106-2112.
  • Lennon VA, Kryzer TJ, Pittock SJ, et al. IgGmarker of optic-spinal multiple sclerosis bindsto the aquaporin-4 water channel. J Exp Med.2005;202:473-477.
  • Sinclair C, Kirk J, Herron B, et al. Absence ofaquaporin-4 expression in lesions of neuromyelitisoptica but increased expression in multiple sclerosislesions and normal-appearing white matter. ActaNeuropathol. 2007;113:187-194.
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