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Anti-Ganglioside Antibodies in a Large Cohort of European Patients with Systemic Lupus Erythematosus: Clinical, Serological, and HLA Class II Gene Associations

MAURO GALEAZZI, PASQUALE ANNUNZIATA, GIAN DOMENICO SEBASTIANI, FRANCESCA BELLISAI, VALERIA CAMPANELLA, GIAN BATTISTA FERRARA, JOSEP FONT, FREDERIC HOUSSIAU, GIUSEPPE PASSIU, ENRIQUE DE RAMON GARRIDO, ANTONIO FERNANDEZ-NEBRO, LUISA BRACCI, RAFFAELLA SCORZA, PIETRO PUDDU, ANNA JEDRYKA-GORAL, JOSEF SMOLEN, ANGELA TINCANI, CARLO CARCASSI, GABRIELLA MOROZZI, ROBERTO MARCOLONGO, and the European Concerted Action on the Immunogenetics of SLE

  ABSTRACT.

 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, aß2-glycoprotein I (aß2-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, aß2GPI, or ANCA.

  Conclusion. Our results show aGM1 can be found in patients with SLE. aGM1 may play a pathogenetic role for some NPM in this condition. (J Rheumatol 2000;27:135–41)

  Key Indexing Terms:
ANTI-GM1
HLA
SYSTEMIC LUPUS ERYTHEMATOSUS
NEUROPSYCHIATRIC MANIFESTATIONS



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