ABSTRACT
OBJECTIVE: To determine whether the allelic frequency variation of the HS1.2 enhancer of the immunoglobulin heavy chain (IgH) 3' regulatory region (3'RR-1) locus represents a risk factor for systemic lupus erythematosus (SLE) and to identify a possible functional difference in the two most frequent alleles (*1 and *2) in binding nuclear factor- κB (NF-κB) and Sp1. METHODS: The frequency of the enhancer HS1.2 alleles was determined in two cohorts of patients with SLE (n=293) and in 1185 controls. Electrophoretic mobility shift assays (EMSA) were carried out with B cell nuclear extracts with different probes of HS1.2 alleles *1 and *2 to map the consensus binding sites of the nuclear factors. A confirmatory cohort of 121 patients with SLE was also included. RESULTS: The frequency of allele *2 of the HS1.2 enhancer was significantly increased in patients with SLE compared with controls (OR 1.60, 95% CI 1.33 to 1.92, p<0.001). EMSA experiments showed the presence of the Sp1 binding site in both alleles whereas only allele *2 carried the consensus for the NF-κB factor. The presence versus absence of allele *2 in patients with SLE correlated with a higher concentration of IgM levels and with the expression of B cell activating factor receptor (BAFF-R). CONCLUSIONS: The increased frequency of allele *2 in patients with SLE identifies a new genetic risk factor for SLE. A possible biological effect of the polymorphism could be the difference observed in the localisation of an NF-κB binding site which is specific for allele *2 and absent in allele *1. These observations suggest a functional effect of the HS1.2 enhancer in this disease.
Subject(s)
Genetic Predisposition to Disease , Immunoglobulin Heavy Chains/genetics , Lupus Erythematosus, Systemic/genetics , Polymorphism, Genetic , Adult , Base Sequence , Electrophoretic Mobility Shift Assay , Female , Gene Frequency , Humans , Immunoglobulins/genetics , Male , Molecular Sequence Data , NF-kappa B/genetics , Risk FactorsABSTRACT
OBJECTIVE: Rheumatoid arthritis (RA) is the most common inflammatory disorder affecting the cervical spine. The purpose of this study was to characterize the atloaxial involvement with magnetic resonance imaging (MRI) in patients with early RA at the moment of diagnosis and after 18 months of a tight control therapy. METHODS: Twenty consecutive patients with early RA without cervical symptoms and 20 healthy controls were enrolled. The patients underwent unenhanced and enhanced gadolinium MRI study of the upper cervical spine at diagnosis and after 18 months of therapy. The presence of pannus tissue at MRI was considered active synovitis. RESULTS: Five (25%) of the 20 patients presented craniocervical involvement with active synovitis at MRI. At onset, patients with cervical involvement presented higher levels of erythrocyte sedimentation rate, a higher swollen joint count, and a higher Disease Activity Score in 44 joints level. All 5 patients (100%) with cervical involvement presented already peripheral erosions. After 18 months, 1 of 5 patients with atloepistrophic synovial involvement at baseline presented complete regression of the enhancement of synovial periodontoid process, and 1 presented a decrease of this enhancement. None of the patients developed erosive process at the odontoid. The only patient with complete regression of the enhancement presented a very early disease (<3 months). CONCLUSION: Our study demonstrates involvement of the atloaxial junction in 25% of early RA patients, in particular in patients with active and erosive arthritis. An early diagnosis and aggressive treatment with a combination therapy, aiming for remission, does not always reduce atlantoaxial synovitis.
Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Atlanto-Axial Joint/pathology , Magnetic Resonance Imaging , Synovitis/diagnosis , Synovitis/drug therapy , Adult , Aged , Atlanto-Axial Joint/diagnostic imaging , Case-Control Studies , Chi-Square Distribution , Contrast Media , Drug Therapy, Combination , Early Diagnosis , Female , Humans , Italy , Male , Meglumine/analogs & derivatives , Middle Aged , Organometallic Compounds , Predictive Value of Tests , Radiography , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Skin ulcers are common vascular complications of systemic sclerosis (SSc). OBJECTIVE: The aim of the study was to identify clinical, biologic, and imaging parameters that constitute risk factors for the occurrence and persistence of skin ulcers. METHODS: One hundred thirty Italian SSc patients were examined at entry and after 20 months of follow-up. RESULTS: The diffuse SSc phenotype with avascular areas on capillaroscopy, thrombophilia, and systemic inflammation as defined by interleukin 6 plasma levels, represented the major risk factors for ulcer development. Infection was associated with a risk of poor or no healing, and cardiopulmonary involvement was a major comorbid factor in patients with ulcers. The presence of infection and avascular areas represented the main determinants for ulcer healing. LIMITATIONS: Our data should be confirmed with a longer follow-up period since skin ulcers represent a frequent vascular complication in scleroderma patients. CONCLUSION: Aggressive therapies aiming at improving angiogenesis and controlling infection and the course of the disease appear to be crucial to obtain ulcer healing.
