Association of Silica Exposure with Anti–Neutrophil Cytoplasmic Autoantibody Small-Vessel Vasculitis

Abstract

Anti-neutrophil cytoplasmic autoantibodies (ANCA) are associated with a category of small-vessel vasculitis (SVV) with frequent glomerulonephritis. The goal of this study was to evaluate the association of lifetime silica exposure with development of ANCA-SVV, with particular attention to exposure dosage, intensity, and time since last exposure. A southeastern United States, population-based, case-control study was conducted. Case patients had ANCA-SVV with pauci-immune crescentic glomerulonephritis. Population-based control subjects were frequency-matched to case patients by age, gender, and state. Jobs were assessed in a telephone interview. Silica exposure scores incorporated exposure duration, intensity, and probability for each job and then were categorized as none, low/medium, or high lifetime exposure. Logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Silica exposure was found in 78 (60%) of 129 case patients and in 49 (45%) of 109 control subjects. There was no increased risk for disease from low/medium exposure relative to no exposure (OR 1.0; 95% CI 0.4 to 2.2) but increased risk with high exposure (OR 1.9; 95% CI 1.0 to 3.5; P ‫؍‬ 0.05). Crop harvesting was associated with elevated risk (OR 2.5; 95% CI 1.1 to 5.4; P ‫؍‬ 0.03). However, both agricultural and traditional occupational sources contributed to the cumulative silica exposure scores; therefore, the overall effect could not be attributed to agricultural exposures alone. There was no evidence of decreasing by duration of time since last exposure. High lifetime silica exposure was associated with ANCA-SVV. Exposure to silica from specific farming tasks related to harvesting may be of particular importance in the southeastern United States. Interval of time since last exposure did not influence development of ANCA-SVV.

Dysregulation of Autoantigen Genes in ANCA-Associated Vasculitis Involves Alternative Transcripts and New Protein Synthesis

“…28 AAV has provided a model for discovery of characteristic features of autoimmune diseases. Investigations exemplify how environmentally triggered effects [29][30][31][32] might alter epigenetic mechanisms 33 that result in a deviation in expression and availability of the actual autoantigens recognized in disease.…”

Wegener’s granulomatosis and environmental factors in Western Montana

“…2 However, descriptive epidemiological studies identifying geographic variation, and other studies identifying seasonal differences in WG onset, have suggested that environmental factors also play a role in WG etiology. [2][3][4][5][6][7][8][9][10] Environmental exposures can affect ANCA production. For example, persons with chronic exposure to ambient silica more commonly have elevated serum ANCA titers with MPO antibodies.…”

“…3,4 In addition, the results of several case-control studies have suggested that occupational history of inhaled ambient silica is a risk factor for developing AAV. [5][6][7][8] Other case-control studies have observed an association between exposure to metals, solvents, and pesticides and AAV occurrence. 8,11,12 While studies have identified the contribution of smoking to the development of rheumatoid factor and seropositive rheumatoid arthritis, studies of other immune-mediated disorders have failed to identify a clear influence of cigarette smoking on their development.…”

Novel association of the CD226 (DNAM-1) Gly307Ser polymorphism in Wegener's granulomatosis and confirmation for multiple sclerosis in German patients

“…1,2 With a prevalence of approximately 24-157 per million in European populations, WG is rare. 3 WG is most likely of multifactorial origin primed by a complex interaction of extrinsic (for example, exposure to Staphylococcus aureus or crystalline silica 4,5 ) and genetic factors. A major genomic risk locus for WG has been identified on chromosome 6p21.3 including the HLA-DPB1 gene.…”