The role of metals in autoimmune vasculitis: epidemiological and pathogenic study

Background: A possible relationship between Silica ŽSi. exposure and antineutrophil cytoplasm antibodies ŽANCA.-associated vasculitis has been reported. Furthermore, tuberculosis ŽTBC. has been frequently described in patients with silicosis, and TBC infection shares with ANCA-associated vasculitis the formation of granulomas. Therefore, an intriguing network including Silica, Vasculitis, TBC and ANCA might be hypothesized. The aim of this work was to further investigate these correlations using both epidemiological and pathogenic approaches. Methods: Study I epidemiological study. A case control study to compare the occupational histories of 31 cases of biopsy proven vasculitis Ž18 pauci-immune crescentic glomerulonephritis, 9 microscopic polyangitis, 4 Wegener’s granulo- matosis. with those of 58 age, sex and residence-matched controls Žaffected by other kidney diseases., was performed. Occupational Health physicians designed an appropriate questionnaire in order to evaluate a wide spread of exposures and calculate their entity by the product of Intensity Frequency Duration. Study II tuberculosis association. A case control study to evaluate the frequency of a previous history of tuberculosis ŽTBC. in 45 patients with vasculitis and 45 controls were performed. Study III ANCA positi ity. A case control study to evaluate the presence of ANCA was performed by testing blood samples of 64 people with previous professional exposure and 65 sex age matched patients hospitalized in a General Medicine Unit. Furthermore, the same evaluation was made in a pilot study in 16 patients with ongoing or previous TBC. Study IV experimental study. The oxygen free radicalsŽOFR. and IL-12 production Žboth involved in the pathogenesis of vasculitis. from human phagocytic cells stimulated with an amorphous Ždiatomaceous earth. and a crystalline Žquartz. form of Si at the doses of 10 and 100 g ml 1 was evaluated. Results: Study I a positive history of exposure to Si resulted in significantly more present in cases Ž14 31 45%. than in controls Ž14 58 24%, P 0.04, OR 2.4. and no other significant exposure association was found Žincluding asbestos, mineral oil, formaldehyde, diesel and welding fumes, grain and wood dust, leather, solvents, fungicides, bitumen, lead and paint.. Study II past TBC infection was significantly more present in patients with vasculitis Ž12 45 26%. than in controls Ž4 45 8%, P 0.05.. Study III ANCA was present in 2 64 exposed people Žvs. 0 65 controls, P NS. and 0 16 patients with TBC. Study IV both amorphous and crystalline Si forms represented a stimulus for OFR and IL-12 production, but quartz resulted as a greater inductor. Conclusions: We conclude that Si exposure might be a risk factor for ANCA-associated vasculitis, possibly enhancing endothelial damage by phagocyte generation of oxygen free radicals and Th1 differentiation by an excessive IL-12 phagocyte production. Frequency of TBC was significantly higher in vasculitis patients. ANCA was not frequent in the preliminary examination of people with previous professional exposure or patients with TBC, but the number of samples evaluated is too small to allow conclusions.