Silica and Asbestos Exposure in ANCA-Associated Vasculitis with Pulmonary Involvement

Rihova, Zuzana; Maixnerová, Dita; Jančová, Eva; Pelclová, Daniela; Bartůňková, Jiřina; Fenclová, Zdeňka; Vankova, Zdenka; Reiterová, Jana; Merta, M; Ryšavá, R; Tesař, Vladimı́r

doi:10.1080/08860220500200395

Cited by 37 publications

(20 citation statements)

References 16 publications

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“…Several case-control studies have shown that among patients with AAV, a high percentage (20 to 45%) were previously exposed to silica [22], [23], [24], [25], [26], [27], [28], [29]. However, these studies have been difficult to interpret; factors such as small numbers of cases and diverse forms of classification for silica exposure contribute to this difficulty, as do the varying strengths of association between AAV and silica that are reported.…”

Section: Introductionmentioning

confidence: 99%

The association between silica exposure and development of ANCA-associated vasculitis: Systematic review and meta-analysis

Gómez-Puerta

Gedmintas

Costenbader

2013

Autoimmunity Reviews

137

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Background Crystalline silica is among the environmental exposures associated with increased risk of autoimmune diseases, including rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus. Silica exposure has also been related to the development of ANCA-associated vasculitides (AAV), but past studies appear to conflict as to the presence and magnitude of the associated risks of disease. We aimed to conduct a systematic review of the existing studies and meta-analysis of their results. Methods We searched EMBASE, MEDLINE and international scientific conference abstract databases for studies examining the association of silica exposure with AAV. Studies in English, French, or Spanish were included and those examining the association of silica with ANCA-positivity alone were excluded. We assessed study quality using the Newcastle-Ottawa scale. We meta-analyzed the results using random effects models and tested for heterogeneity. We performed sensitivity and subgroup analyses, examining studies that adjusted for smoking and occupational risk factors as well as studies that analyzed by subtypes of AAV. Results We identified 158 potential manuscripts and 3 abstracts related to silica exposure and risk of AAV. 147 were excluded after abstract review and 14 underwent detailed evaluation of full manuscript/abstract. After further application of exclusion criteria, 6 studies (all case-controls) remained. The studies had moderate heterogeneity in selection of cases and controls, exposure assessment, disease definition and controlling for potential confounders. We found an overall significant summary effect estimate of silica “ever exposure” with development of AAV (summary OR 2.56, 95% CI 1.51- 4.36), with moderate heterogeneity (I2=48.40%). ORs were similar for studies examining only MPA (OR 3.95, CI 95% 1.89-8.24), compared to those only studying GPA (OR 3.56, CI 95% 1.85-6.82). Conclusion Despite moderate heterogeneity among studies, the totality of the evidence after meta-analysis points to an association between silica exposure and risk for developing AAV.

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Section: Introductionmentioning

confidence: 99%

The association between silica exposure and development of ANCA-associated vasculitis: Systematic review and meta-analysis

Gómez-Puerta

Gedmintas

Costenbader

2013

Autoimmunity Reviews

137

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“…An association with ANCA-associated vasculitis has been described in two studies of asbestos exposures [50, 51] but was not found in at least one study despite an association with silica exposure [52]. Because the interstitial pneumonia that is common in this form of vasculitis can be mistaken for asbestosis, this link may simply be overlooked.…”

Section: Systemic Autoimmune Disease (Said) and Asbestosmentioning

confidence: 99%

“…Few studies have attempted to identify specific targets for asbestos-induced ANA, but one commonality has been the presence of anti-dsDNA in both mice and humans [20, 40, 78], but not rats [41]. Antibodies to neutrophils (ANCA) have been associated with silica and asbestos exposure [51, 79], but the asbestos exposure data came from an occupational exposure questionnaire, so the exposures likely included mixed chrysotile and amphibole. Pfau et al did not find an association with ANCA in their amphibole-exposed cohort [20].…”

Section: Targets Of Autoantibodies and Mechanisms Of Diseasementioning

confidence: 99%

Autoimmunity and Asbestos Exposure

Pfau

Serve

Noonan

2014

Autoimmune Diseases

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Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA), a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a) a lack of statistical power due to relatively small or diffuse exposure cohorts, (b) exposure misclassification, (c) latency of clinical disease, (d) mild or subclinical entities that remain undetected or masked by other pathologies, or (e) effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease.

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“…Silica is a risk factor for ANCA disease (51,52). ANCA disease can be caused by drugs, including propylthiouracil, hydralazine, D-penicillamine, allopurinol, minocycline and anti-TNF agents (7,8,53).…”

Section: Origin Of the Anca Autoimmune Responsementioning

confidence: 99%

Pathogenesis of antineutrophil cytoplasmic autoantibody vasculitis

Jennette¹,

Falk

Gasim³

2011

Current Opinion in Nephrology and Hypertension

115

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Purpose of Review Anti-neutrophil cytoplasmic autoantibodies (ANCA) are associated with vasculitis. Current therapy involves administration of toxic therapy that is not optimally effective. The review will summarize evidence for the pathogenicity of ANCA, which will suggest possible strategies for improving treatment. Recent Findings Pauci-immune small vessel vasculitis is associated with antibodies against myeloperoxidase (MPO-ANCA) and proteinase 3 (PR3-ANCA). One research group has reported a high frequency of autoantibodies against lysosomal-associated membrane protein 2 (LAMP-2) in patients with MPO-ANCA or PR3-ANCA. Epigenetic dysregulation appears to be the basis for increased MPO and PR3 neutrophil gene expression in ANCA disease. Release of neutrophil extracellular traps (NETS) may be involved in initiating the ANCA autoimmune response and causing vessel injury. Generation of C5a by alternative pathway activation is involved in pathogenesis in mouse models. Intervention strategies in mice that target antigens, antibodies and inflammatory signaling pathways may translate into novel therapies. Animal models of LAMP-ANCA and PR3-ANCA disease have been proposed. Molecular mimicry and responses to complementary peptides may be initiating events for ANCA. T cells, including regulatory T cells, have been implicated in the origin and modulation of the ANCA, as well as in the induction of tissue injury. Summary Our basic understanding of the origins and pathogenesis of ANCA disease is advancing. This deeper understanding already has spawned novel therapies that are being investigated in clinical trials. This brief review shows that there are more questions than answers, and new questions are emerging faster than existing questions are being answered.

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Silica and Asbestos Exposure in ANCA-Associated Vasculitis with Pulmonary Involvement

Cited by 37 publications

References 16 publications

The association between silica exposure and development of ANCA-associated vasculitis: Systematic review and meta-analysis

The association between silica exposure and development of ANCA-associated vasculitis: Systematic review and meta-analysis

Autoimmunity and Asbestos Exposure

Pathogenesis of antineutrophil cytoplasmic autoantibody vasculitis

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