PMID- 30585624 OWN - NLM STAT- MEDLINE DCOM- 20200218 LR - 20200501 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 196 IP - 2 DP - 2019 May TI - Bronchoalveolar lavage characteristics correlate with HLA tag SNPs in patients with Lofgren's syndrome and other sarcoidosis. PG - 249-258 LID - 10.1111/cei.13257 [doi] AB - Genetic susceptibility for sarcoidosis and Lofgren'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. CI - (c) 2018 British Society for Immunology. FAU - Karakaya, B AU - Karakaya B AD - Department of Pulmonology, ILD Center of Excellence, St Antonius Hospital, Nieuwegein, the Netherlands. FAU - Schimmelpennink, M C AU - Schimmelpennink MC AUID- ORCID: 0000-0003-3222-1644 AD - Department of Pulmonology, ILD Center of Excellence, St Antonius Hospital, Nieuwegein, the Netherlands. FAU - Kocourkova, L AU - Kocourkova L AD - Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic. FAU - van der Vis, J J AU - van der Vis JJ AD - Department of Pulmonology, ILD Center of Excellence, St Antonius Hospital, Nieuwegein, the Netherlands. AD - Department of Clinical Chemistry, ILD Center of Excellence, St Antonius Hospital, Nieuwegein, the Netherlands. FAU - Meek, B AU - Meek B AD - Medical Immunology and Microbiology Department, St Antonius Hospital, Nieuwegein, the Netherlands. FAU - Grutters, J C AU - Grutters JC AD - Department of Pulmonology, ILD Center of Excellence, St Antonius Hospital, Nieuwegein, the Netherlands. AD - Division of Heart and Lungs, University Medical Center, Utrecht, the Netherlands. FAU - Petrek, M AU - Petrek M AD - Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic. AD - University Hospital Olomouc, Olomouc, the Czech Republic. FAU - van Moorsel, C H M AU - van Moorsel CHM AD - Department of Pulmonology, ILD Center of Excellence, St Antonius Hospital, Nieuwegein, the Netherlands. AD - Division of Heart and Lungs, University Medical Center, Utrecht, the Netherlands. LA - eng PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20190124 PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (HLA-DRB1 Chains) RN - 0 (HLA-DRB1*15 antigen) SB - IM MH - Adult MH - *Alleles MH - Bronchoalveolar Lavage MH - *CD4-Positive T-Lymphocytes/immunology/pathology MH - *CD8-Positive T-Lymphocytes/immunology/pathology MH - Genotyping Techniques MH - *HLA-DRB1 Chains/genetics/immunology MH - Humans MH - Male MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - *Sarcoidosis, Pulmonary/genetics/immunology/pathology PMC - PMC6468184 OTO - NOTNLM OT - MHC OT - T cells OT - lung COIS- The authors declare no potential conflicts of interest. EDAT- 2018/12/27 06:00 MHDA- 2020/02/19 06:00 PMCR- 2020/05/01 CRDT- 2018/12/27 06:00 PHST- 2018/12/08 00:00 [accepted] PHST- 2018/12/27 06:00 [pubmed] PHST- 2020/02/19 06:00 [medline] PHST- 2018/12/27 06:00 [entrez] PHST- 2020/05/01 00:00 [pmc-release] AID - CEI13257 [pii] AID - 10.1111/cei.13257 [doi] PST - ppublish SO - Clin Exp Immunol. 2019 May;196(2):249-258. doi: 10.1111/cei.13257. Epub 2019 Jan 24.