This regional study conducted in the eastern part of Turkey examined silicosis caused by denim sandblasting with the goal of reporting its associations with class I and class II human leukocyte antigens because a role of HLA has been shown in many inflammatory diseases. Our study showed that , although A23, B49, and B51 were more common in the mild group than in the severe group , and B55 and DR4 were more common in the severe group, B51 was the only statistically significant difference between the two groups. By comparing the latency period and HLA antigens there was no statistical difference between groups. The main difference between our study and previous researches consists in that we compared HLA types according to disease severity and latency. To our best knowledge, this is the first time these comparisons are done and no previous report on this issue has been published.
In literature, although there are a few reports showing that certain HLA antigens are more common incases of silicosis, none of them has found association between silicosis and any HLAs. Reported HLA type, common or uncommon, varies among the studies. Kreiss et al. [8] reported an increased frequency of HLA-B44 and HLA-A29 among 49 silicotic subjects by comparison with 1,029 white North American individuals without silicosis. In another study, they reported that Aw19 and B18 were increased [12]. In a similar study, Gualde et al. [13] reported that there was no significant association between HLAs and silicosis among the 75 patients in their 1977 study; however, they noted a decrease in the frequency of B7. In addition, they reported an increase in B8 among silicotic patients with tuberculosis, although only in a small number of patients. They only focused on comparing the HLAs of patients with silicosis and healthy controls. However, we aimed to focus on a possible association betweenHLA type and both disease severity and latency because HLA is closely associated with immunologic reactions, which may speed up the course of silicosis.
Shih et al. [7] investigated the association between asbestosis, which is another form of pneumoconiosis like silicosis, and HLA; they reported a higher prevalence of HLA-DRw53 and DQ2 in subjects with asbestos-induced pleural fibrosis. The presence of HLA-DQ2 was significantly related to the extent and type of asbestos-induced pleural fibrosis while HLA-DRw53 was not consistently related to the type or extent of pleural disease. Importantly, they observed that HLA-A29, HLA-B44, HLA-Bw4, HLA-DRw53, and HLA-DQ2 were not associated with a significantly shorter duration or latency of asbestos exposure. This study suggests that HLA may play a role in the progression of the disease and may shorten the latency period.
In our study the increased B51 in the mild silicosis group may suggest its anti-inflammatory role. This could also be linked to a lower sensitivity to silica exposure among people who carry this antigen. However, it is difficult to conclude that HLA-B51 has a negative effect on inflammation because there is an association between Behçet disease (BD) and HLA-B51. It plays a role in the pathogenesis of this auto-inflammatory disease, which includes oral and genital ulcerations, uveitis, and skin involvement as the main inflammatory alterations, and it has been strongly associated with the disease among different ethnic groups [14]. The prevalence of the HLA-B51 antigen in ethnic groups varies from 0% to more than 25%. Populations with a high HLA-B51 prevalence (> 10%) are predominantly located in the Middle East, Greece, Turkey, Iran, and Japan [15]. While B51 is identified in an average of 15–20% of the healthy population in Turkey, in BD this ratio increased to 50–60%. It has been shown that the frequency of BD increases in populations with increased HLA-B51 [14, 16]. However, according to our findings, it is difficult to reach such a conclusion because B51 occurs more frequently in the mild group.
In our study, HLA-B55 and DR4 were increased in the severe group, but the increases were not statistically significant. Ayako et al. [17] showed that the frequencies of HLA-DRB1*0406 were significantly higher in patients with silicosis (16.67%) than in healthy individuals (3.03%). In another study, HLA-B55 and DR4 were significantly increased in patients with Vogt-Koyanagi-Harada syndrome (which is a systemic disorder characterized by depigmentary inflammation of melanocyte-containing tissues in Koreans) compared with a control group [18]. For this reason, they may impact the severity of the disease.
One of the reasons for the predominance of different HLAs among the studies previously described may result from HLA polymorphisms. HLA is very polymorphic and might also exist across populations of different ethnicities [16]. The fact that HLA polymorphisms exist in different groups suggests that it is important to evaluate as many different populations as possible to determine specific protective or predisposing factors for silicosis or a range of diseases associated with inflammation [19]. This is compatible with the hypothesis that environmental factors affect the regional distribution of certain HLA alleles [20]. Therefore, we can assume that the association between class I and class II HLAs and developing silicosis may differ among ethnic groups.
The main limitations of our study were the limited number of cases and the presentation of all cases from the same local region. Studies with larger sample sizes and cases from different regions will be required to show a stronger relationship. However, we had no opportunity to conduct such study because the majority of cases with silicosis caused by denim sandblasting were from the same few regions. Exposure to silica is highly associated with the working environment and there is a tendency for work in the same places among the workers from different regions. Thus, studying workers from different ethnic groups and diverse regions would be another confounding factor because of heterogeneity of exposure, that is highly associated with the disease severity and latency.