%0 Journal Article %A B. Karakaya %A C.H.M. van Moorsel %A G.T. Rijkers %A A.H.M. van der Helm %A T.W.J. Huizinga %A J.M.M. van den Bosch %A J.C. Grutters %T Polymorphisms in CCR5 confer susceptibility to Löfgren's syndrome and may regulate the immune response %D 2011 %J European Respiratory Journal %P 4517 %V 38 %N Suppl 55 %X Rationale: Löfgren's syndrome is an acute and usually self-remitting phenotype of sarcoidosis. Several studies have found associations between specific gene polymorphisms and susceptibility to sarcoidosis.Chemokines are small peptides that mediate monocyte, lymphocyte and neutrophil chemotactic activity by binding to specific G-protein coupled receptors, such as CCR5. A study showed that the HHC haplotype of CCR5, with single nucleotide polymorphism (SNP) rs1799987, was associated with Löfgren's syndrome.Objective: We investigated if SNPs of the CCR5 gene were associated with Löfgren's syndrome and had an effect on the B-lymphocyte response of patients.Methods: Hunderd and twenty patients with Löfgren's syndrome were characterized and genotyped for 4 SNPs in CCR5. Our control cohort consisted of 313 self-reported healthy individuals.Calcium mobilization response to MIP-1a, a ligand of CCR5, was measured in peripheral blood B-lymphocytes of 18 Löfgren's syndrome patients (3 male and 15 female) and 3 controls.Results: Carriage of the G-allele was significantly higher in patients with Löfgren's syndrome than in healthy controls (p=0.00557, CI 1.13-2.01, OR 1.505).Twelve out of 18 patients with Löfgren's syndrome showed no calcium response, of which 11 were carriers of the G-allele: 7 GG, 4 GA, 1 AA. Nine of these 12 patients where women. All controls showed a calcium mobilization response upon stimulation with MIP-1a.Conclusions: The SNP rs1799987 in the CCR5 genes is associated with Löfgren's syndrome. Functionality assays showed that polymorphisms of the CCR5 have an impact on cellular processes that may regulate the response of B-lymphocytes. %U