Association of the G-463A myeloperoxidase gene polymorphism with renal disease in African Americans with systemic lupus erythematosus.

OBJECTIVE: Myeloperoxidase (MPO) is an enzyme expressed in neutrophils that is involved in tissue damage in inflammatory renal diseases. A functional G to A single-nucleotide polymorphism (SNP) is present at position -463 of the MPO promoter region and is associated with altered MPO expression. We hypothesized that the G-463A MPO SNP is a risk factor for developing lupus nephritis (LN) due to its potential influence on the inflammatory response. METHODS: DNA from 229 patients with SLE and 277 controls from the Carolina Lupus cohort, 58 African American patients from the Sea Island Lupus Cohort, and 51 African American patients from the Lupus Multiplex Registry and Repository were genotyped by PCR. A linear regression model was used to examine relationships between the MPO genotype, case/control status, demographic characteristics, and LN. RESULTS: There was no association of MPO genotype with systemic lupus erythematosus (SLE). However, the odds of developing LN were significantly higher among those with an A allele, compared to those without, in African American cases of all 3 cohorts. When the likelihood of developing LN was compared across MPO genotypes, the risk of developing LN was significantly higher among cases with a GA genotype versus GG (OR 2.11, 95% CI 1.12 to 3.97) and even higher with AA versus GG (OR 3.52, 95% CI 1.41 to 8.77). CONCLUSION: While the G-463A MPO SNP is not a risk factor for developing SLE, the low expressing A allele is a significant risk factor for developing LN that is gene dosage-dependent in African Americans.

Postprandial stomach contents have multiple acid layers.

GOALS: The purpose of this study was to evaluate patterns in gastric pH both fasting and postprandially in different body positions. STUDY: Ten healthy volunteers were studied. A pH probe was positioned with an electrode 15 cm below the lower esophageal sphincter proximal border then withdrawn 1 cm every 30 seconds to 5 cm above the lower esophageal sphincter. Volunteers were tested on 2 occasions. Initially, they were studied in a semirecumbent position (45 degrees), with the first pull-through after 6 hour fasting. After a meal, a pull-through was repeated 4 consecutive times (approximately 15, 30, 45, and 60 min). On a subsequent day, the positions were changed with each pull-through: upright, supine, right decubitus, and left decubitus. The order of these positions was randomly selected. RESULTS: The pH step-up is defined as a change in pH from a gastric to an esophageal pH (<4-->>4). No significant difference was found between location of the pH step-up in the fasting and postprandial pull-throughs. An area of lower pH was consistently found within 2 cm distal to the step-up area. Distal to the area of higher gastric pH (median pH at 5), a second acid layer was found. This pattern persisted through the 4 postprandial pull-throughs, irrespective of body position. CONCLUSIONS: The pH step-up was persistent in the fasting period and for 1 hour postprandially, but did not migrate proximally. Gastric buffering from a meal creates a nonuniform environment with at least 2 acid layers. This pattern is present irrespective of body position. The lack of homogeneity of stomach content postprandially helps to explain the observation of occasional persistent acid gastroesophageal reflux after a meal.

Vitamin D deficiency in systemic lupus erythematosus.

Evidence from animal models and prospective studies of RA, multiple sclerosis, and type-1 diabetes suggest an important role for vitamin D as a modifiable environmental factor in autoimmune disease. This role has not been well studied in human SLE. We compared serum 25-hydroxyvitamin D (25(OH)D) levels between recently diagnosed SLE cases and matched controls, and examined disease characteristics in relationship to 25(OH)D among cases. Data from a population-based cohort of 123 recently diagnosed SLE patients and 240 controls were used. We found a trend toward lower 25(OH)D levels in cases compared to controls, which was statistically significant in Caucasians (p=0.04), controlling for age, sex, season, and smoking. Overall, 67% of the subjects were vitamin D deficient, with mean levels significantly lower among African Americans (15.9 ng/ml) compared to Caucasians (31.3 ng/ml). Critically low vitamin D levels (<10 ng/ml) were found in 22 of the SLE cases, with presence of renal disease being the strongest predictor (OR 13.3, p<0.01) followed by photosensitivity (OR 12.9, p<0.01). These results suggest vitamin D deficiency as a possible risk factor for SLE and provide guidance for future studies looking at a potential role of vitamin D in the prevention and/or treatment of SLE.

New therapies and preventive strategies to treat and minimize damage in lupus.

Systemic lupus erythematosus is a complex disease characterized by a loss of immune tolerance leading to autoantibody production, immune complex deposition in target organs, and resultant tissue damage. There are currently only three medications approved for the treatment of lupus; hydroxychloroquine, aspirin, and prednisone. This limited spectrum of medications is contrasted by the dozen clinical trials in lupus underway or planned for the next 2 years. These new therapeutic agents hold promise for being more effective with fewer side effects than the current available agents. Increased awareness of co-morbid diseases in lupus is also leading to new approaches for the prevention of "disease damage" in lupus.

Pigmented villonodular synovitis: a disease in evolution.

Pigmented villonodular synovitis (PVNS) is a rare, benign, proliferative disease of the synovial membrane of joints, tendon sheaths, and bursas. Joint aspiration typically yields hemorrhagic or xanthochromic/serosanguinous (brown, murky) fluid. We describe a case of PVNS that presented as an acute, painless, nontraumatic right knee effusion with clear synovial fluid on arthrocentesis. Initial magnetic resonance imaging of the knee revealed no evidence for hemosiderin. A diagnostic arthroscopy and surgical arthrotomy revealed a unique case of PVNS evolving from local to diffuse involvement of the synovium.