HLA class I and class II frequencies in patients with sarcoidosis from Croatia: role of HLA‐B8, −DRB1*0301, and −DQB1*0201 haplotype in clinical variations of the disease

Abstract

Sarcoidosis is an immune-mediated, multiorgan, granulomatous disease triggered by a combination of environmental and genetic factors. Numerous studies have reported about an association of human leukocyte antigen (HLA) alleles with sarcoidosis, with variation of alleles in different ethnic groups. Therefore, we investigated 142 Croatian sarcoidosis patients treated at the University Hospital for Lung Diseases Jordanovac, Zagreb, Croatia. Diagnosis was based on the presence of typical clinical features, chest X-ray findings and biopsy evidence of granuloma. Patients and control subjects (n = 190) were typed for HLA class I antigens by serology, while for HLA class II, they were tested by the polymerase chain reaction-sequence specific primers (PCR-SSP) method. Results indicated that HLA-B8, -DRB1*0301, and -DQB1*0201 positive patients have a significantly higher risk of acute onset of the disease (AOD), radiological stage I erythema nodosum (EN), Löfgren's syndrome, no-medicament therapy, and pulmonary sarcoidosis. On the other hand, the group of non-treated patients (corticosteroids and/or immunosuppressive) showed a significantly lower presence of HLA-B15 antigen in comparison to controls and treated patients (P = 0.0490 and P = 0.0379, respectively) and for DRB1*04 specificity (P = 0.0078 and P = 0.0065, respectively). In the group of patients with AOD, those who were positive for DRB1*16 specificity have a statistically significant chance to develop EN, as opposed to those who are positive for DRB1*15 specificity.

HLA-DRB1 allele frequencies and C4 copy number variation in Finnish sarcoidosis patients and associations with disease prognosis

“…Previously, in various Caucasian populations, DRB1*15 and the haplotype HLA-DRB1*15:01-DQB1*06:02 have been demonstrated to be associated with the persistent form of sarcoidosis [11,15,[17][18][19]36,37]. In this study the persistent subgroup exhibited only nominal association with the DRB1*15:01 allele.…”

HLA‐alleles associated with increased risk for extra‐pulmonary involvement in sarcoidosis

“…In sarcoidosis, there are reports about associations to both HLA class I and II genes as well as to non‐HLA genes . The role of linkage disequilibrium (LD), defined as the tendency for genetic variants located close to each to be associated within a population more often than if they were unlinked, has been discussed in sarcoidosis as well as in other diseases.…”

Pathogenesis of sarcoidosis

“…Some results have been demonstrated across studies and different racial and ethnic groups. For example, HLA-DRB1*03 has been consistently associated with spontaneous resolution and mild disease as demonstrated in Swedish [56], Polish [73], Croatian [74], Czech [75], and Finish populations [76]. A striking influence of DRB1*03 on the disease course has been shown in a distinct subgroup of sarcoidosis patients, with Löfgren's syndrome [18].…”