Bronchoalveolar lavage characteristics correlate with HLA tag SNPs in patients with Löfgren’s syndrome and other sarcoidosis

• Published in: Clinical and experimental immunology 2019-05, Vol.196 (2), p.249-258
• Main Authors: Karakaya, B., Schimmelpennink, M. C., Kocourkova, L., Vis, J. J., Meek, B., Grutters, J. C., Petrek, M., Moorsel, C. H. M.
• Format: Article
• Language: English
• Subjects: Adult; Alleles; Alveoli; Bronchoalveolar Lavage; Bronchus; CD103 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Cell number; Drb1 protein; Flow cytometry; Genotypes; Genotyping; Genotyping Techniques; Histocompatibility antigen HLA; HLA-DRB1 Chains - genetics; HLA-DRB1 Chains - immunology; Humans; lung; Lymphocytosis; Male; MHC; Middle Aged; Original; Phenotypes; Polymorphism, Single Nucleotide; Prognosis; Sarcoidosis; Sarcoidosis, Pulmonary - genetics; Sarcoidosis, Pulmonary - immunology; Sarcoidosis, Pulmonary - pathology; Single-nucleotide polymorphism; T cells
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.13257

Summary Genetic susceptibility for sarcoidosis and Löfgren’s syndrome (LS) has been associated with prognosis. Human leukocyte antigen (HLA)‐DRB1*03 is over‐represented in LS, and is associated with a good prognosis, whereas HLA‐DRB1*15‐positive patients have a more chronic course of sarcoidosis. These HLA‐DRB1 types can be easily tagged by single nucleotide polymorphisms (SNPs). Our aim was to evaluate the association between these tag SNPs and bronchoalveolar lavage (BAL) characteristics. In 29 patients, both complete HLA‐DRB1* locus genotyping and SNP tagging was performed in parallel. HLA‐DRB1 type was inferred from the presence of *03 tag rs2040410 allele A and referred to as *03. HLA‐DRB1*15 was inferred from the presence of tag SNP rs3135388 allele A and referred to as *15. For BAL analysis, 122 patients with LS and 165 patients with non‐LS sarcoidosis were included. BAL lymphocyte subsets were analyzed by flow cytometry. The presence of tag SNPs completely corresponded with HLA‐DRB1*03/*15 genotypes in all 29 patients in whom both HLA‐DRB1* genotyping and SNP tagging was performed. In all patients together, *03+/*15– patients showed a higher CD4+/CD8+ ratio than *03–/*15+ (P = 0·004) and *03–/*15– (P = 0·001). LS patients with *03+/*15– had a lower BAL lymphocyte count compared to *03–/*15+ patients (P = 0·011). Non‐LS sarcoidosis patients with *03+/*15– patients showed a decreased CD103+CD4+/CD4+ ratio compared to *03–/*15+ patients (P = 0·045) and *03–/*15– patients (P = 0·018). We found that HLA‐DRB1*03 and HLA‐DRB1*15 can be approximated by genotyping of tag SNPs and corresponds with the degree of lymphocytosis and cell phenotypes in BAL in both LS and non‐LS sarcoidosis patients. In this study we evaluated the use of tag SNPs for human leukocyte antigen (HLA)‐DRB1*03 and HLA‐DRB1*15 in sarcoidosis patients. Furthermore, we investigated association between the tag SNPs of HLA‐DRB1*03 and HLA‐DRB1*15 and BAL characteristics in patients with Löfgren’s syndrome (LS) and non‐LS sarcoidosis patients. The results showed that HLA‐DRB1*03 and HLA‐DRB1*15 can be approximated by genotyping of tag SNPs and corresponds with the degree of lymphocytosis and cell phenotypes in BAL in LS and non‐LS sarcoidosis patients.