Mercury-exposed platinum miners were demonstrated to have a higher prevalence of detectable ANA as compared to diamond and emerald miners with no occupational mercury exposure(113) and two case-control studies have shown elevated risk of SLE associated with self-reported exposure to mercury(35, 98)

Mercury-exposed platinum miners were demonstrated to have a higher prevalence of detectable ANA as compared to diamond and emerald miners with no occupational mercury exposure(113) and two case-control studies have shown elevated risk of SLE associated with self-reported exposure to mercury(35, 98). Sex, Hormonal, and Reproductive Factors Female sex is definitely a strongly predisposing factor in SLE susceptibility and the overwhelming majority of SLE instances occur among women during childbearing years(114, 115). urinary neopterin, a macrophage activation marker and indication of SLE disease activity(53). Additionally, antioxidants such as resveratrol or humulones in wine and beer influence cytokines such as interferon-gamma and may inhibit important enzymes involved in DNA synthesis (54, 55). Moderate alcohol intake may also reduce serum levels of IgG (56). Finally, alcohol usage may induce epigenetic changes, resulting in modified gene manifestation that could impact LY 255283 immune homeostasis(57). Epidemiologic studies of alcohol usage and SLE risk again have hadconflicting results(18, 51, 58C60). A subsequent meta-analysis of six case-control studies and one cohort study (including studies of SLE individuals treated for 10 years) LY 255283 proven a significantly protecting effect of moderate alcohol intake on SLE risk (OR 0.72, 95%CI 0.55C0.95)(19). Recently, we have found a strong inverse relationship between long-term moderate alcohol usage (5 grams or 0.5 drink/day time) and event SLE (HR 0.61, 95%CI 0.41C0.89) among women in the Nurses Health Study cohorts(61**). As wine was the most common alcoholic beverage consumed by these ladies, those who drank 2 servings of wine/week had significantly decreased SLE risk (HR 0.65; 95%CI 0.45C0.96), compared to ladies who did not drink wine. Radiation and Nutritional Factors Ultraviolet (UV) Radiation Although UV radiation CD34 exposure may exacerbate pre-existing SLE, it remains unclear whether UV exposure plays a role in the pathogenesis of SLE(62). Experimental studies suggest that UV-B radiation results in induction of reactive oxygen species, leading to DNA damage(63), production of novel forms of autoantigens and autoreactive T cells(64, 65), and may possess immunomodulatory effects on T cells and cytokines (66, 67), all potentially involved in to SLE pathogenesis. Only a few case-control studies have been able to examine UV radiation exposure and risk of SLE(68C70), and these have been limited by potential inaccuracy of exposure assessment, and affected by recall and reverse causation bias, given that photosensitivity due to SLE can be present well before analysis. We have recently reviewed this topic in detail elsewhere(71). Large, well-controlled studies are still needed to prospectively assess the relationship of UV-B radiation with event SLE. Vitamin D Further complicating our understanding of the relationship between UV radiation and SLE pathogenesis is the controversial role of Vitamin D. While exposure to solar UV radiation may result in SLE disease flares, UV light exposure is also the main source of vitamin D production(72). Vitamin D LY 255283 may be immunosuppressive once metabolized to 1 1,25(OH)2D3(73), and it has been suggested that UV-B radiation could reduce SLE risk via activation of cutaneous vitamin D synthesis(74C76). Many cross-sectional and case-control studies possess reported low 25(OH) vitamin D concentrations in SLE individuals compared to settings, however, it is not obvious whether low vitamin D is definitely a cause or result of chronic disease. No protective effect of vitamin D intake from foods or health supplements was found amon women in the Nurses Health Studies (76, 77). Infections Epstein-Barr disease (EBV) seropositivity rates are much higher in adults and children with SLE than age-matched settings(24, 25). Potential mechanisms LY 255283 involve EBV RNA/SSB protein complexes inducing type 1 interferon via Toll-like receptor 3 (78) and molecular mimicry between EBV and SLE antigens(28, 79). Additionally, SLE individuals have impaired CD8+ cytotoxic T cells, and irregular cytokine production in plasmacytoid dendritic cells and CD69+CD4+ T cells in response to EBV(80, 81). However, no conclusive data have established that EBV illness is linked to LY 255283 future risk of SLE. Notably, in a large population-based Danish cohort, EBV-serologic bad individuals experienced a sustained improved risk for SLE highest in the 1 to 4 years after screening (standardized incidence rate, 6.6; 95% CI, 3.3C13.2), but this getting may have been due to a monitoring bias while EBV testing is likely to be performed during the work-up for early SLE symptoms(82). In that study, no associations were found with EBV serologic positivity, infectious mononucleosis, or severe infectious mononucleosis requiring hospitalization (82, 83). A recent meta-analysis of twenty-five case control studies shown a statistically significant higher seroprevalence of anti-viral capsid antigen IgG (OR 2.08, 95% CI 1.15 to 3.76, p = 0.007) and antibodies to EBV.