Activation of humoral immunity and eosinophils in neuromyelitis optica.
OBJECTIVE
To study immunologic alterations in patients with neuromyelitis optica (NMO).


METHODS
The authors studied 8 patients with NMO together with 16 healthy subjects, 16 patients with relapsing remitting multiple sclerosis (RRMS), and 16 patients with secondary progressive MS (SPMS), matched for age and sex, as controls. Because recent histopathologic studies have demonstrated that active NMO lesions consist of perivascular immunoglobulin (Ig) deposition and eosinophil infiltration, IL-5, IL-6, IL-12, IgG, and IgM production by anti-myelin oligodendrocyte glycoprotein (MOG) mononuclear cells in peripheral blood and CSF were selected for study using ELISPOT. Eotaxin-2 (Eo-2) and eotaxin-3 (Eo-3) levels were also assessed using ELISA and eosinophil cationic protein (ECP) levels by radioimmunoassay.


RESULTS
MOG-specific responses in CSF showed significant increase in IL-5, IL-6, IgG, and IgM secreting cells in NMO patients compared with patients with RRMS, SPMS and healthy subjects. Interestingly, numbers of IgM secreting cells were significantly higher than identical specificity IgG secreting ones. Moreover, CSF Eo-2, Eo-3, and ECP levels were also significantly higher in NMO patients compared to all three control populations. Anti-MOG IL-12 secreting cells were increased in CSF and peripheral blood from NMO, RRMS, and SPMS patients when compared to healthy subjects.


CONCLUSIONS
These observations suggest that neuromyelitis optica is associated with a major humoral immune response (particularly anti-MOG IgM production) and eosinophil activation present exclusively in CSF.
Correale
Jorge
J
Raúl Carrea Institute for Neurological Research, FLENI, Montañeses 2325 (1428), Buenos Aires, Argentina. jcorreale@fleni.org.ar
Fiol
Marcela
M
D000328:Adult; D000917:Antibody Formation; D001323:Autoantibodies / Q000097:blood*; D020274:Autoimmune Diseases of the Nervous System / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000097:blood / Q000134:cerebrospinal fluid; D002631:Chemotactic Factors, Eosinophil / Q000097:blood / Q000134:cerebrospinal fluid; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism; D015848:Interleukin-5 / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D007958:Leukocyte Count; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009471:Neuromyelitis Optica / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*
D001323:Autoantibodies; C515484:CCL24 protein, human; C120429:CCL26 protein, human; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015848:Interleukin-5; D015850:Interleukin-6; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D018664:Interleukin-12