HLA class II DNA typing in a large series of European patients with systemic lupus erythematosus: correlations with clinical and autoantibody subsets

We conducted this study to determine the HLA class II allele associations in a large cohort of patients of homogeneous ethnic derivation with systemic lupus erythematosus (SLE). The large sample size allowed us to stratify patients according to their clinical and serologic characteristics. We studied 577 European Caucasian patients with SLE. Antinuclear antibodies (Hep-2 cells), anti-dsDNA antibodies (Crithidia luciliae), and antibodies to extractable nuclear antigens Ro (SS-A), La (SS-B), U1-RNP, Sm, Jo1, SCL70, and PCNA, were detected in all patients. Molecular typing of HLA-DRB1, DRB3, DQA1, and DQB1 loci was performed by the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method. We found a significantly increased frequency of DRB1*03, DRB1*15, DRB1*16, DQA1*0102, DQB1*0502, DQB1*0602, DQB1*0201, DQB1*0303, and DQB1*0304 in lupus patients as compared with healthy controls. In addition, DRB1*03 was associated with anti-Ro, anti-La, pleuritis, and involvement of lung, kidney, and central nervous system. DRB1*15 and DQB1*0602 were associated with anti-dsDNA antibodies; DQB1*0201 with anti-Ro and anti-La, leukopenia, digital skin vasculitis, and pleuritis; and DQB1*0502 was associated with anti-Ro, renal involvement, discoid lupus, and livedo reticularis. In conclusion, our study shows some new HLA clinical and serologic associations in SLE and further confirms that the role of MHC genes is mainly to predispose to particular serologic and clinical manifestations of this disease

Treat-to-target in systemic lupus erythematosus: recommendations from an international task force.

The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet points were analysed for degree of agreement among the task force. The Oxford Centre level of evidence (LoE, corresponding to the research questions) and grade of recommendation (GoR) were determined for each recommendation. The 12 systematic literature searches and their summaries led to 11 recommendations. Prominent features of these recommendations are targeting remission, preventing damage and improving quality of life. LoE and GoR of the recommendations were variable but agreement was >0.9 in each case. An extensive research agenda was identified, and four overarching principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative. It is anticipated that 'treating-to-target' can and will be applicable to the care of patients with SLE

Anticardiolipin and antibeta2GPI antibodies In a large series of european patients with systemic lupus erythematosus: prevalence and clinical association.

OBJECTIVE: To test the prevalences and the clinical associations of anticardiolipin (aCL) and anti-beta2GPI (abeta2GPI) antibodies in a large series of European patients with systemic lupus erythematosus (SLE). METHODS: 574 SLE patients from 7 European countries were tested for aCL and abeta2GPI by ELISA methods. RESULTS: aCL of IgG, IgM, and IgA isotypes were detected in 22.8%, 14%, and 13.9% of the patients, respectively. IgG and IgM abeta2GPI were detected in 20% of the patients. The presence of aCL was highly associated with the presence of abeta2GPI. Medium-high titer IgG aCL and abeta2GPI were associated with thrombosis, with similar sensitivity, specificity, and positive predictive value. When present at medium-high titer, IgG aCL were associated with thrombocytopenia, IgM aCL with hemolytic anemia, and cerebrovascular accidents. IgA aCL with livedo reticularis and Raynaud's phenomenon. CONCLUSIONS: aCL, when present at medium-high titer, are as important as abeta2GPI, as a risk factor for thrombosis. Medium-high titer aCL, but not abeta2GPI, are associated with other clinical features of the antiphospholipid syndrome

HLA class II alleles associations of anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus

The objective of this study was to determine the HLA class II associations of the anticardiolipin (aCL) and anti-beta2GPI (abeta2GPI) antibodies in a large series of European patients with systemic lupus erythematosus (SLE). A cohort of 577 European SLE patients was enrolled. aCL and abeta2GPI were measured by ELISA methods. Molecular typing of HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1 loci was performed by the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method. aCL of IgG, IgM and IgA isotypes were detected in 22.8%, 14% and 13.9% of patients, respectively. IgG and IgM abeta2GPI were detected in 20% of patients. aCL showed positive association with HLA DRB1*04, DRB1*0402, DRB1*0403, DRB1*07, DRB3*0301, DQA1*0201, DQA1*0301, DQB1*0302, and negative association with DQA1*0501, DRB3*0202. abeta2GPI showed positive association with DRB1*0402, DRB1*0403, DQB1*0302. DRB1*0402 carried the highest relative risk for the presence of both aCL (RR=8. 1) and abeta2GPI (RR=4.6). Our results confirm the already described associations of aCL with HLA DR4 and DR7, but also demonstrate that, among the alleles at the DRB1*04 locus, the *0402 was most represented both in aCL and in abeta2GPI positive patients. In addition, HLA class II associations of abeta2GPI are for the first time extensively examined in a large cohort of European SLE patients

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. CONCLUSION: Our results show aGM1 can be found in patients with SLE. aGM1 may play a pathogenetic role for some NPM in this condition