Functional predictions and protein network analyses suggest a prominent role of the drug-targetable IL23/Th17 signaling pathway in the genetic etiology of sarcoidosis. Our findings reveal a substantial genetic overlap of sarcoidosis with diverse immune-mediated inflammatory disorders, which could be of relevance for the clinical application of modern therapeutics.

Sarcoidosis is a granulomatous disorder showing a clear association with MHC (HLA) class I and class II genes. In order to investigate whether polymorphisms of nearby pro-inflammatory genes located within the MHC class III region may also contribute to susceptibility to sarcoidosis or to its clinical manifestation, tumour necrosis factor-alpha (TNF-alpha) and lymphotoxin-alpha (LT-alpha) genes were chosen for analysis in a case-control association study. In order to evaluate the findings on the TNF-alpha and LT-alpha genes in connection with the closely linked MHC class II region, 'classical' HLA-DRB1 locus was also investigated. Polymerase chain reaction-based methodologies were used in order to characterize two single-nucleotide polymorphisms (TNF-308*G/A and LTAlpha+252*A/G) and HLA-DRB1 allele groups in 114 Czech patients with pulmonary sarcoidosis and 425 healthy controls. LTA+252*G and HLA-DRB1*13 allele carriers were more frequent in patients, compared to those in controls. By contrast, HLA-DRB1*07 carriers were less frequent among sarcoidosis patients. The overrepresentation of TNF-308*A, LTAlpha+252*G and HLA-DRB1*03 allele carriers was found in a subgroup of sarcoidosis patients presenting with Lofgren's syndrome (LS) by comparison with the subgroup of patients without LS (NLS; phenotype frequency LS vs NLS: 68.8 vs 37.1% for TNF-308*A, 93.8 vs 66.3% for LTA+252*G and 68.8 vs 21.3% for DRB1*03). The data suggest that the LTAlpha and HLA-DRB1 genes themselves or a gene located nearby contributes to the susceptibility to sarcoidosis and that TNF-308*A, LTA+252*G and HLA-DRB1*03 alleles are associated (directly or via linkage with unknown causative locus) with LS as a specific manifestation of the disease.

Background: For accuracy of quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), normalisation with suitable reference genes is required. To date, no reference genes have been validated for expression studies of bronchoalveolar (BAL) cells. The aims of this study were to identify gene(s) with stable mRNA expression in BAL cells irrespective of gender, smoking, BAL cellular composition, lung pathology, treatment; and to assess the influence of reference genes on target gene expression data.

No abstract

Surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy enables determination of protein patterns in sarcoid BALF and allows detection of protein patterns linked to a particular disease course.

Background: The differences in total hip arthroplasty (THA) survivorship may be influenced by individual susceptibility to periprosthetic osteolysis. This may be driven by functional polymorphisms in the genes for cytokines and cytokine receptors involved in the development of osteolysis in THA, thereby having an effect on the individual's phenotype.

Various polymorphisms of non-HLA genes have recently been investigated as candidate risk factors in allogeneic haematopoietic SCT (aHSCT). Our study aimed at exploring possible associations of IL6 and CCL2 single nucleotide polymorphisms (SNP) with aHSCT outcome. A total of 166 HLA-identical aHSCT pairs recruited in were genotyped for IL6 À174 G/C, IL6 À597 G/A, CCL2 À2518 A/G and CCL2 À2076 A/T SNPs by PCR with sequence-specific primers (PCR-SSP). The association between IL6 À174 GG genotype and increased risk of acute GVHD was found in whole study group (P ¼ 0.03) and in the subgroup of related aHSCT (P ¼ 0.01), association between IL6 À597 GG genotype and the occurrence of acute GVHD was detected only in the related aHSCT pairs (P ¼ 0.02). Furthermore, reduction in OS was revealed among recipients possessing IL6 À174*G allele in the group of related aHSCT pairs (P ¼ 0.04). Presence of CCL2 À2076 TT genotype was associated with decrease of OS (P ¼ 0.04) and increase of TRM (P ¼ 0.02) in patients transplanted by related donor. These results, in the context of previous findings, suggest that IL6 gene polymorphisms may be associated with aHSCT outcome, particularly in patients transplanted from a related donor.

For the first time, we confirmed the association of HLA-DRB1*15 with RBC antibody multiresponder status and found HLA-Class II associations for three frequent RBC antibody combinations. Our data support the concept that HLA restriction plays an important role in the response to RBC alloantigens.