Anti-ganglioside antibodies in a large cohort of European patients with systemic lupus erythematosus: clinical, serological, and HLA class II gene associations. European Concerted Action on the Immunogenetics of SLE.
OBJECTIVE
To assay anti-ganglioside antibodies (aGM1) in sera of a large cohort of European patients with systemic lupus erythematosus (SLE) to define the prevalence of these autoantibodies in SLE; to evaluate the association of aGM1 with clinical manifestations and other autoantibodies found in SLE; and to search for aGM1 association with HLA class II alleles.


METHODS
Four hundred forty-eight patients with SLE were consecutively enrolled in 8 centers from 6 European countries. All sera were tested for antinuclear antibodies by immunofluorescence on HEp-2 cells as substrate, anti-dsDNA, aGM1, aCL, abeta2-glycoprotein I (abeta2-GPI) antibodies by ELISA, and antineutrophil cytoplasmic antibodies (ANCA) by immunofluorescence and by ELISA. Genomic typing for HLA class II loci was performed by polymerase chain reaction-sequence specific oligonucleotide probe method. Clinical assessment was done at the time of enrolment.


RESULTS
We found 41.9% of patients with clinical signs of neuropsychiatric involvement; 15.5% of patients were positive for aGM1, 8% of the IgG isotype and 8.6% of the IgM isotype; aGM1-IgG were associated with neuropsychiatric manifestations (NPM) (RR = 3.7), with migraine (RR = 2.4), with OBS (RR = 7.3), and with peripheral neuropathy (RR = 8.5). aGM1-IgM were associated with NPM (RR = 4) and with depression (RR = 3.4). Furthermore, the genetic study showed that aGM1-IgG were associated with HLA-DQB1*0404 (RR = 7.2) while aGM1-IgM were associated with HLA-DQB1*0605 (RR = 33.3). No associations were found between aGM1 and anti-dsDNA, aCL, abeta2GP1, or ANCA.


CONCLUSIONS
Our results show aGM1 can be found in patients with SLE. aGM1 may play a pathogenetic role for some NPM in this condition.
Galeazzi
M
M
Istituto di Reumatologia, Universita di Siena, Italy.
Annunziata
P
P
Sebastiani
G D
GD
Bellisai
F
F
Campanella
V
V
Ferrara
G B
GB
Font
J
J
Houssiau
F
F
Passiu
G
G
De Ramon Garrido
E
E
Fernandez-Nebro
A
A
Bracci
L
L
Scorza
R
R
Puddu
P
P
Jedryka-Goral
A
A
Smolen
J
J
Tincani
A
A
Carcassi
C
C
Morozzi
G
G
Marcolongo
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D015331:Cohort Studies; D005060:Europe; D005260:Female; D005732:Gangliosides / Q000276:immunology*; D005802:Genes, MHC Class II / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000150:complications / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology
D001323:Autoantibodies; D005732:Gangliosides