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

Our plain-English summary of The role of metals in autoimmune vasculitis: epidemiological and pathogenic study, by P. Stratta, A. Messuerotti, C. Canavese, et al (The Science of the Total Environment, 2001).

The study

• Authors: P. Stratta, A. Messuerotti, C. Canavese, M. Coen, L. Luccoli, B. Bussolati, L. Giorda, P. Malavenda, M. Cacciabue, M. Bugiani, M. Bo, M. Ventura, G. Camussi, B. Fubini
• Journal: The Science of the Total Environment
• Published: 2001;270(1-3):179-90
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: A possible relationship between Silica (Si) exposure and antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis has been reported. Furthermore, tuberculosis (TBC) 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 (18 pauci-immune crescentic glomerulonephritis, 9 microscopic polyangitis, 4 Wegener's granulomatosis) with those of 58 age, sex and residence-matched controls (affected 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 x Frequency x Duration. Study II--tuberculosis association. A case-control study to evaluate the frequency of a previous history of tuberculosis (TBC) in 45 patients with vasculitis and 45 controls were performed. Study III--ANCA positivity. 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 radicals (OFR) and IL-12 production (both involved in the pathogenesis of vasculitis) from human phagocytic cells stimulated with an amorphous (diatomaceous earth) and a crystalline (quartz) form of Si at the doses of 10 and 100 microg ml(-1) was evaluated.

Results: Study I--a positive history of exposure to Si resulted in significantly more present 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 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 (12/45 = 26%) than in controls (4/45 = 8%, P < 0.05). Study III--ANCA was present in 2/64 exposed people (vs. 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.

In plain English

This study from the University of Turin, Italy, had four parts. It looked at possible links between silica exposure, tuberculosis, and kidney-related vasculitis, a disease in which blood vessels become inflamed, often with ANCA antibodies in the blood. In the main case-control study, the authors compared the job histories of 31 patients with biopsy-proven renal vasculitis and 58 matched patients with other kidney diseases. Silica exposure was reported by 14 of 31 cases (45%) and 14 of 58 controls (24%), with P = 0.04 and an odds ratio of 2.4. No other exposure, including asbestos, differed significantly between the groups. The authors noted that asbestos exposure was unexpectedly higher in controls than in cases. Past tuberculosis was found in 12 of 45 vasculitis patients and 4 of 45 controls (P less than 0.05). ANCA was found in 2 of 64 previously exposed workers (one exposed to silica, one to asbestos) and in none of 65 hospital controls, a difference that was not statistically significant. In laboratory tests, quartz stimulated white blood cells more strongly than diatomaceous earth. The authors concluded that silica exposure may be related to renal vasculitis. They named the retrospective design and small numbers as limits.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Four-part study: a retrospective case-control study of occupational exposures (Study I), a case-control study of past tuberculosis (Study II), a case-control comparison of ANCA blood tests with a pilot group of tuberculosis patients (Study III), and a laboratory experiment on human white blood cells exposed to silica dusts (Study IV)
• Who was studied: Study I: 31 of 61 patients with renal-related vasculitis who had a renal biopsy at the Department for Nephrology, University of Turin, between 1976 and 1998 (only those still alive or traceable could be evaluated), and 58 controls with other kidney diseases matched for sex, age and region of residence. Study II: 45 vasculitis patients and 45 matched controls with other kidney diseases. Study III: 64 people with previous occupational exposure (44 exposed to silica dust, 20 exposed to asbestos), 65 patients in the Geriatric Medicine Unit as controls, and a pilot group of 16 patients with tuberculosis
• Exposure: Mainly silica and asbestos exposure, assessed by a structured questionnaire and scored blindly by an industrial hygienist (degree x frequency x duration). Other substances were also assessed, including metals, welding fumes, diesel and petrol exhaust, oils, grain and wood dust, leather dust, formaldehyde, bitumen and solvents. The asbestos fiber type is not specified. The laboratory part used crystalline silica (Min-U-sil quartz) and amorphous silica (diatomaceous earth, aerosil)
• Main results:
  • Silica exposure was more frequent in vasculitis cases (14/31 = 45%) than in controls with other kidney diseases (14/58 = 24%), P = 0.04, odds ratio 2.4
  • No other exposure showed a significant association with vasculitis, including asbestos, mineral oil, formaldehyde, diesel and welding fumes, grain and wood dust, leather, solvents, fungicides, bitumen, lead and paint
  • Unlike silica, asbestos exposure was unexpectedly higher among controls than among vasculitis cases (no numbers given in the text)
  • Any occupational exposure to pollutants did not differ significantly: 22/31 vasculitis cases (70%) and 36/58 controls (62%), P = 0.54
  • Overt clinical silicosis was diagnosed in only three vasculitis patients, and silica exposure intensity was low in both groups with no difference between them
  • Past tuberculosis was more frequent in vasculitis patients (12/45, printed as 26%) than in controls (4/45, printed as 8%), P less than 0.05
  • ANCA was found in 2 of 64 previously exposed people, compared with 0 of 65 controls (not statistically significant) and 0 of 16 tuberculosis patients. Both positives were P-ANCA at a moderate level
  • Of the two ANCA-positive exposed people, one was among the 44 silica-exposed subjects and one among the 20 asbestos-exposed subjects
  • In laboratory tests, both amorphous and crystalline silica stimulated oxygen free radical and IL-12 production by human white blood cells, but quartz was the stronger stimulus
• The authors' conclusion: The authors concluded that silica exposure may be related to vasculitis with kidney involvement, even without overt silicosis. They also concluded that the number of ANCA samples was too small to allow conclusions
• Limitations the authors state:
  • The retrospective case-control design
  • A still relatively low number of cases
  • The tuberculosis analysis was based on a small sample
  • Too few ANCA samples were evaluated to allow conclusions
  • From epidemiological data alone, it was difficult to determine what type of silica patients had been exposed to

Topics

Medical terms in this study, explained in our Lexicon: Silicosis, Granuloma, Case-Control Study, Biopsy, Crystalline.

Related studies

• Nested case-control study of autoimmune disease in an asbestos-exposed population — C.W. Noonan, J.C. Pfau, et al. (2006)
• Silica and asbestos exposure in ANCA-associated vasculitis with pulmonary involvement — Z. Rihova, D. Maixnerova, et al. (2005)
• Indications for distinct pathogenic mechanisms of asbestos and silica through gene expression profiling of the response of lung epithelial cells — T.N. Perkins, P.M. Peeters, et al. (2015)
• Antibody producing cells in the spleens of mice treated with pathogenic mineral dust — S. Szymaniec, D.M. Brown, et al. (1989)
• Asbestos exposure and antineutrophil cytoplasmic Antibody (ANCA) positivity — D. Pelclová, J. Bartůnková, et al. (2003)
• An epidemiological study in an Anatolian village environmentally exposed to tremolite asbestos — Y.I. Baris, N. Bilir, et al. (1988)

Browse more research in The Science of the Total Environment, or return to medical research.