engleski

HLA-DRB1 Alleles In Croatian Sarcoidosis Patients

Sarcoidosis is a heterogeneous multisystem granulomatous disease that primarily affects the lungs. Numerous studies have reported an association of HLA alleles with sarcoidosis, with variation of alleles in different ethnic groups. Therefore, to identify the significance of HLA alleles in the development of sarcoidosis in the Croatian population, we investigated the HLA-DRB1 alleles in patients and healthy control subjects. Ninety patients with sarcoidosis were diagnosed at the Clinical Hospital for Lung diseases Jordanovac, Zagreb. Diagnosis was based on the presence of typical clinical features, chest X-ray findings and biopsy evidence of granuloma. As a control group we used 141 untreated healthy individuals. All subjects were typed for HLA-DRB1 polymorphism by PCR-SSP method. 1) Analysis of DRB1 alleles between all patients and controls showed significant differences and higher frequencies only for DRB1*0301 allele (p=0.0023), while lower frequencies of DRB1*07 and DRB1*13 alleles were marginally significant. (Fig.1.) 2) Patients were divided into two groups according to the onset of sarcoidosis: a) acute onset of disease (N=34) ; b) chronic onset of disease (N=56). Allele DRB1*0301 was significantly more frequent among patients with acute onset of disease in comparison with controls (18.6 % vs. 6.4% ; p=0.0021), while DRB1*11 was significantly more frequent in patients with chronic onset of disease in comparison with controls (28.1% vs. 15.6% ; p=0.0051). Differences in distribution of DRB1*11 alleles among two patient's groups did not reach significant p value (Fig. 2.) 3) The distribution of HLA-DRB1 alleles into two groups of patients classified on the basis of the chest X-ray stage is presented in the Figure 3. Patients with chest X-ray stage I (N=34) showed significant higher presence of DRB1*0301 alleles in comparison to controls (20.6% vs. 6.4% ; p=0.00064), but not in comparison with patients with chest X-ray stage II or III ( 20.6% vs. 12.5%, p>0, 05). On the other hand, patients with chest X- ray stage II or III showed significantly higher presence of DRB1*11 allele when compared to controls ( 26.8% vs. 15.6% ; p=0.015), but not in comparison with the patients with chest X-ray stage I (26.8% vs. 17.7%, p>0.05). 4) Among 36 patients with acute or chronic skin sarcoidosis DRB1*0301 allele was also present with statistically significant higher frequency compared with controls (23.6% vs. 6.4% ; p=0.00004)(Fig. 4). Patients with no skin sarcoidosis showed significantly higher frequency of DRB1*11 allele ( 26.9% vs. 15.6% ; p=0.0164) and lower frequency of DRB1*13 allele (4.6 vs. 12.8% ; p=0.0253). Out of 19 patients (21.1%) with EN, 9 patients (47.4%) were DRB1*0301 positive. DISCUSSION Our data on the association of DRB1*0301 allele and acute form of disease are in good agreement with Scandinavian and German studies in which association with HLA-DR3 was also observed. Those studies as well as the studies from UK, Poland and Czech Republic have also reported that DRB1*14 and DRB1*15 as more frequent among these patients, but that is not the case among ours pts. Increased frequency of DRB1*11 allele observed among Croatian patients with chronic onset of sarcoidosis and chest X-ray stage II or III is in concordance with data from USA and India. This study demonstrates that DRB1*0301 positive patients have higher risk for acute onset of the disease, radiological stage I and skin sarcoidosis, especially EN, and that DRB1*11 positive patients have higher risk for developing chronic onset of the disease and radiological stage II and III. Interpolating these findings with known data on the predictors of outcome, we suggest that HLA-DRB1 associated alleles could be used as possible predictors of outcome in sarcoidosis patients.

Sarcoidosis; HLA genes

Sarcoidosis Vasculitis and Diffuse Lung Diseases