Certain Metals, Silica Can Cause Immune Response in Sarcoidosis, Study Finds

More than 20% of sarcoidosis patients show signs of an immune system response against aluminum, beryllium, zirconium, and silica, supporting the idea that these compounds may be involved in the development of the disease in a subgroup of patients, according to findings from a research study.

The study, “Immunoreactivity to metal and silica associates with sarcoidosis in Dutch patients,” was published in the journal Respiratory Research.

Sarcoidosis is a condition in which the immune system is overactive, leading to inflammatory cells bundling together and forming structures called granulomas that can harden over time and cause permanent damage to tissues and organs.

Previous studies have provided evidence that certain metals as well as silica can elicit a response from the immune system in sarcoidosis patients, contributing to the development of the condition.

Researchers in the Netherlands and Belgium therefore collaborated on a study to more closely examine the relationship between sarcoidosis and these compounds.

“The combination of occupational exposure and an immunological reaction has not been studied before in a group of sarcoidosis patients and non-sarcoidosis controls,” the researchers wrote.

The study analyzed a group of sarcoidosis patients who had previously visited the Interstitial Lung Disease Center of Excellence at the St. Antonius Hospital in Nieuwegein, the Netherlands. For comparison, a control group comprised of patients at the same hospital who had been diagnosed with obstructive sleep apnea (OSA) were included. OSA was chosen as its development is not caused by environmental triggers.

To assess potential exposure to metals and silica, all patients were sent a questionnaire about their complete job history. Each job description was matched with a description in the International Standard Classification of Occupations 1968, which categorizes jobs into seven major groups with subdivisions for any unique job title.

A total of 256 sarcoidosis patients and 74 OSA patients responded to the questionnaire and were included in the study.

Risk of exposure to silica or other metals was assigned through the DOM-JEM, a matrix designed in the Netherlands for population studies to associate job titles with exposure risks.

Results showed that 83 sarcoidosis patients (32.4%, 83 out 256 patients) had occupational exposure to silica or metals, compared to 18 control participants (24.7%).

Of the exposed patients, 33 with sarcoidosis and 19 from the control group were invited to perform what is called a lymphocyte proliferation test (LPT) — a test to determine whether a person exhibits an immune response to a specific compound.

In LPT, a blood sample is drawn from the subject, and lymphocytes — white blood cells, important agents of the immune system — are collected. Lymphocytes are then incubated for five days in a medium that also contains the compound of interest, and their growth rate is analyzed.

In this case, the compounds analyzed were beryllium, aluminum, zirconium, and silica.

In total, seven of the 33 sarcoidosis patients (21.2%) showed a specific reaction to the tested metals or silica, compared to none in the control group.

One sarcoidosis patient reacted to aluminum, three to beryllium, two to zirconium, and two to silica. One of these patients showed an immune response to both zirconium and beryllium.

However, the researchers found that occupational exposure did not predict the possibility of reacting to metals or silica, nor did the severity of sarcoidosis in the patients.

“Almost half of our patients with a positive LPT were classified by JEMs as unexposed,” the researchers wrote. “Since job history with assigned exposure did not differ between sarcoidosis patients and controls, our data indicate that even very low incidence or occasional exposures could be relevant in sarcoidosis patients.”

Overall, based on the results, metals and silica can cause an immune reaction in certain sarcoidosis patients, and that this may contribute to the development of the disease in some cases, the team said.

“Immunoreactivity to silica and metals found in sarcoidosis patients only, supports the hypothesis that these antigens may be involved in the disease pathogenesis of a distinct subgroup of sarcoidosis patients,” the researchers wrote.

Further studies are however needed to “clarify underlying immunological pathways and mechanisms in order to establish a more definitive role for these antigens in sarcoidosis,” the team added.