Pneumologie 2012; 66 - P4_007
DOI: 10.1055/s-0032-1329833

Associations of HLA-DRB1 genotype with clinical expression of sarcoidosis portuguese patients

S Neves 1, D Lopes 2, A Morais 3, C Carvalho 2, A Bettencourt 2, B Leal 2, P Mota 3, M Brito 1, S Torres 1, S Maia 2, P Pinho e Costa 4, B Martins da Silva 2
  • 1Pulmonary Medicine Division, Centro Hospitalar Gaia e Espinho, Portugal
  • 2Instituto Ciências Biomédicas Abel Salazar, Portugal
  • 3Hospital São João, Portugal
  • 4Instituto Nacional Ricardo Jorge

Introduction: Sarcoidosis is a granulomatous multisystem disorder of unclear etiology that commonly affects the lungs (90%), heart, skin and central nervous system. There is evidence for a strong genetic predisposition. Several studies conducted in different population have reported association between sarcoidosis and HLA (Human Leukocyte Antigen) class I and class II alleles. In Swedish patients Grunewald et al (Respiratory Research, 2010) reported that HLA-DRB1*15 is associated with a chronic course of sarcoidosis while the presence of HLA-DRB1*01 and HLA-DRB1*04 protect against disease. It has been also described that the HLA-DRB1*03 allele is associated with Lofgren's Syndrome (LS), a distinct form of sarcoidosis. This syndrome is characterized by an acute onset with bilateral hilar lymphadenopathy, erythema nodosum (EN), ankle arthritis and has in general a favorable prognosis.

Objective: To investigate the putative association of HLA-DRB1 with the clinical expression of sarcoidosis in portuguese patients.

Material and methods: A total of 106 patients [64 female and 42 male; mean age of, 50.8 years] and 282 healthy individuals (control group), were genotyped for HLA-DRB1, by PCR-SSP. Twenty patients were classified as Lofgren's Syndrome and 86 as Non Lofgren Syndrome (non-LS). Statistical analyses were performed using the Chi-square or Fisher's exact test.

Results: The frequency of HLA-DRB1*01 allele was significantly decreased in sarcoidosis patients compared with control group (10% vs. 23%, OR=0.379, CI=0.192–0.750, p=0.004). Considering LS and non-LS patients, this allele in non-LS patients was significantly decreased when compared with LS patients (7% vs. 25%, OR=0.225, CI=0.061–0.833, p=0.017). When LS was compared with the control group, the frequency of HLA-DRB1*03 allele was significantly increased in these patients (35% vs. 16%, OR=2.913, CI=1.100–7.710, p=0.025) and the HLA-DRB1*04 allele (5% vs. 24%, OR=0,162, CI=0,021–1,236, p=0,046) was decrease in the same group.

Conclusion: This study reports for the first time an association of HLA-DRB1*01 with LS in sarcoidosis patients. The previously reported association of LS with the HLA-DRB1*03 allele was confirmed. HLA-DRB1*04 could only be confirmed for the LS group, possible due to the small sample size.