Immunoreactivity to metal and silica associates with sarcoidosis in Dutch patients

Abstract

Background: Involvement of metals or silica in the pathogenesis of sarcoidosis has been suggested by several case reports and specific epidemiological studies. However, the combination of occupational exposure and an immunological reaction has not been studied before in a group of sarcoidosis patients and non-sarcoidosis controls. Methods: In 256 sarcoidosis patients and 73 control patients with obstructive sleep apnea, exposure to metal and silica was assessed using a questionnaire consisting of a complete occupational history subsequently linked to jobexposure matrices. Next, immunoreactivity to aluminium, beryllium, zirconium and silica was determined in 33 sarcoidosis and 19 control patients using a lymphocyte proliferation test. Results: In sarcoidosis, 83 out 256 patients (32.4%) had occupational exposure to metals or silica, compared to 24.7% in the control group (p = 0.21). A significantly higher percentage of the sarcoidosis patients tested showed immunoreactivity to metals or silica compared to the control group (21.2 and 0% respectively, p = 0.039). Conclusions: Immunoreactivity to silica and metals was only found in sarcoidosis patients, supporting the hypothesis that these antigens may be involved in the pathogenesis of a distinct subgroup of sarcoidosis patients. This indicates that when searching for causative agents in sarcoidosis patients, besides beryllium, also zirconium, aluminium and silica deserve clinical investigation.

Simultaneous testing of immunological sensitization to multiple antigens in sarcoidosis reveals an association with inorganic antigens specifically related to a fibrotic phenotype

“…It seems plausible to assume that this will also be the case for other inorganic triggers. In a previous paper, we showed that occupational exposure to metal/silica determined by a job exposure matrix (JEM) is not predictive for a positive LPT [19]. A possible explanation may be that the JEMs are designed to be very specific, and will not capture individuals experiencing coincidental high-risk exposure while carrying out low-risk jobs.…”

“…*P-value of any positive LPT SI > 2•0 was calculated using Pearson's χ 2 test; the other P-values were calculated using Fisher's exact test. The two silica-positive patients were also included in a previous study [19]. ELISPOT = enzyme-linked immunospot.…”

Sarcoidosis

“…A difference is that the number of lymphocytes used per test is higher for MELISA (> 1 Â 10 6 cells) than for the conventional LPT (100,000-250,000), a difference that is believed to increase the sensitivity of the MELISA LPT. 37,38 In the analysis by Beijer et al, 37 patients with sarcoidosis in an interstitial lung disease outpatient clinic in The Netherlands were invited to participate in the study. To assess occupational exposures to silica and metals, a JEM was developed for each patient.…”

Sarcoid-like Granulomatous Lung Disease with Subacute Progression in Silicosis

“…Silica exposure has been associated with sarcoidosis or sarcoid-like granulomatous lung disease (8)(9)(10)(11)(12)(13). Epidemiological studies have noted a high incidence of sarcoidosis in patients with silica exposure (10,11).…”

“…Inhalation of beryllium can cause granulomatous lung disease that mimics sarcoidosis (7), and other metals and inorganic dust have also been associated with a granulomatous response (4)(5)(6). Silica might be a trigger for sarcoidlike granulomatous lung disease, and several studies have reported the association between silica exposure and sarcoidosis or sarcoid-like granulomatous lung diseases (8)(9)(10)(11)(12)(13).…”