Anti-ganglioside antibodies in a large cohort of European patients with systemic lupus erythematosus: Clinical, serological, and HLA class II gene associations

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, aβ₂-glycoprotein I (aβ₂-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 aGM:1, 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, aβ₂GPI, 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.