Prevalence and incidence of systemic lupus erythematosus in a population-based registry of American Indian and Alaska Native people, 2007-2009.

OBJECTIVE: Few studies have investigated the epidemiology of systemic lupus erythematosus (SLE) in American Indian and Alaska Native populations. The objective of this study was to determine the prevalence and incidence of SLE in the Indian Health Service (IHS) active clinical population in 3 regions of the US. METHODS: For this population-based registry within the IHS, the denominator consisted of individuals in the IHS active clinical population in 2007, 2008, and/or 2009 and residing in a community in 1 of 3 specified regions. Potential SLE cases were identified based on the presence of a diagnostic code for SLE or related disorder in the IHS National Data Warehouse. Detailed medical record abstraction was performed for each potential case. The primary case definition was documentation in the medical record of ≥4 of the revised American College of Rheumatology criteria for the classification of SLE. Prevalence was calculated for 2007, and the mean annual incidence was calculated for the years 2007 through 2009. RESULTS: The age-adjusted prevalence and incidence of SLE according to the primary definition were 178 per 100,000 person-years (95% confidence interval [95% CI] 157-200) and 7.4 per 100,000 person-years (95% CI 5.1-10.4). Among women, the age-adjusted prevalence was 271, and the age-adjusted incidence was 10.4. The prevalence was highest in women ages 50-59 years and in the Phoenix Area IHS. CONCLUSION: The first population-based lupus registry in the US American Indian and Alaska Native population has demonstrated that the prevalence and incidence of SLE are high. Our estimates are as high as or higher than the rates reported in the US black population.

Epitope-specific immunotherapy of rheumatoid arthritis: clinical responsiveness occurs with immune deviation and relies on the expression of a cluster of molecules associated with T cell tolerance in a double-blind, placebo-controlled, pilot phase II trial.

OBJECTIVE: Induction of immune tolerance to maintain clinical control with a minimal drug regimen is a current research focus in rheumatoid arthritis (RA). Accordingly, we are developing a tolerization approach to dnaJP1, a peptide part of a pathogenic mechanism that contributes to autoimmune inflammation in RA. We undertook this study to test 2 hypotheses: 1) that mucosal induction of immune tolerance to dnaJP1 would lead to a qualitative change from a proinflammatory phenotype to a more tolerogenic functional phenotype, and 2) that immune deviation of responses to an inflammatory epitope might translate into clinical improvement. METHODS: One hundred sixty patients with active RA and with immunologic reactivity to dnaJP1 were enrolled in a pilot phase II trial. They received oral doses of 25 mg of dnaJP1 or placebo daily for 6 months. RESULTS: The dnaJP1 peptide was safe and well-tolerated. In response to treatment with dnaJP1, there was a significant reduction in the percentage of T cells producing tumor necrosis factor alpha and a corresponding trend toward an increased percentage of T cells producing interleukin-10. Coexpression of a cluster of molecules (programmed death 1 and its ligands) associated with T cell regulation was also found to be a prerequisite for successful tolerization in clinical responders. Analysis of the primary efficacy end point (meeting the American College of Rheumatology 20% improvement criteria at least once on day 112, 140, or 168) showed a difference between treatment groups that became significant in post hoc analysis using generalized estimating equations. Differences in clinical responses were also found between treatment groups on day 140 and at followup. Post hoc analysis showed that the combination of dnaJP1 and hydroxychloroquine (HCQ) was superior to the combination of HCQ and placebo. CONCLUSION: Tolerization to dnaJP1 leads to immune deviation and a trend toward clinical efficacy. Susceptibility to treatment relies on the coexpression of molecules that can down-regulate adaptive immunity.