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

Background: A possible relationship between Silica (Si) exposure and antine utrophil cytoplasm antibodies (ANCA)-associated vasculitis has been reporte d. Furthermore, tuberculosis (TBC) has been frequently described in patient s with silicosis, and TBC infection shares with ANCA-associated vasculitis the formation of granulomas. Therefore, an intriguing network including Sil ica, Vasculitis, TBC and ANCA might be hypothesized. The aim of this work w as to further investigate these correlations using both epidemiological and pathogenic approaches. Methods: Study I - epidemiological study. A case-co ntrol study to compare the occupational histories of 31 cases of biopsy pro ven vasculitis (18 pauci-immune crescentic glomerulonephritis, 9 microscopi c polyangitis, 4 Wegener's granulomatosis) with those of 58 age, sex and re sidence-matched controls (affected by other kidney diseases), was performed . Occupational Health physicians designed an appropriate questionnaire in o rder to evaluate a wide spread of exposures and calculate their entity by t he product of Intensity x Frequency x Duration. Study II - tuberculosis ass ociation. A case-control study to evaluate the frequency of a previous hist ory of tuberculosis (TBC) in 45 patients with vasculitis and 45 controls we re performed. Study m - ANCA positivity. A case-control study to evaluate t he presence of ANCA was performed by testing blood samples of 64 people wit h previous professional exposure and 65 sex/age matched patients hospitaliz ed 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 - expe rimental study. The oxygen free radicals (OFR) and IL-12 production (both i nvolved in the pathogenesis of vasculitis) from human phagocytic cells stim ulated with an amorphous (diatomaceous earth) and a crystalline (quartz) fo rm of Si at the doses of 10 and 100 mug ml(-1) was evaluated. Results: Stud y I - a positive history of exposure to Si resulted in significantly more p resent in cases (14/31 = 45%) than in controls (14/58 = 24%, P = 0.04, OR = 2.4) and no other significant exposure association was found (including as bestos, 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 vasculit is (12/45 = 26%) than in controls (4/45 = 8%, P < 0.05). Study III - ANCA w as present in 2/64 exposed people (vs. 0/65 controls, P = NS) and 0/16 pati ents with TBC. Study IV - both amorphous and crystalline Si forms represent ed a stimulus for OFR and IL-12 production, but quartz resulted as a greate r inductor. Conclusions: We concluded that Si exposure might be a risk fact or 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 h igher in vasculitis patients. ANCA was not frequent in the preliminary exam ination of people with previous professional exposure or patients with TBC, but the number of samples evaluated is too small to allow conclusions, (C) 2001 Elsevier Science B.V. All rights reserved.