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Background: In sarcoidosis, the direction and intensity of immunological reactions involved in disease pathophysiology is affected by variation in the genes coding for effector and regulatory molecules with immune functions. This study, therefore, investigates polymorphic variants in genes involved in inflammation, immune reactions, and granuloma formation in context of their plausible association with sarcoidosis, with specific focus on Greek population. Methods: A total of 18 single-nucleotide polymorphisms (SNPs) were genotyped in Greek patients with pulmonary sarcoidosis (n = 103) and in healthy Greek control subjects (n = 100) using multiplexed MassARRAY (MassARRAY ®) iPLEX assay based on MALDI-TOF mass spectrometry. TGF-β3: rs3917200*G variant was associated with sarcoidosis (OR: 3.04 [95% CI: 1.98–4.69], p = 2.76*10−7). Further, ANXA11 rs1049550*A variant was associated with sarcoidosis (OR: 0.59 [0.39–0.89], p = 0.01). Conclusions: This first study of genetic variation of immune-related genes in Greek patients with sarcoidosis brings to attention a novel disease ‘susceptibility’ factor: TGF-β3 rs3917200*G allele. It also confirms previously reported ‘protective’ association between sarcoidosis and functional variant ANXA11 rs1049550*A. Further work is required to validate these findings and to expand investigation of their plausible relationship with clinical course of the disease. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Idiopathic pulmonary fibrosis (IPF) affects lung parenchyma with progressing fibrosis. In this study, we aimed to replicate MUC5B rs35705950 variants and determine new plausible candidate variants for IPF among four different European populations. We genotyped 26 IPF candidate loci in 165 IPF patients from four European countries, such as Czech Republic (n = 41), Germany (n = 33), Greece (n = 40), France (n = 51), and performed association study comparing observed variant distribution with that obtained in a genetically similar Czech healthy control population (n = 96) described in our earlier data report. A highly significant association for a promoter variant (rs35705950) of mucin encoding MUC5B gene was observed in all IPF populations, individually and combined [odds ratio (95% confidence interval); p-value as 5.23 (8.94-3.06); 1.80 × 10-11]. Another non-coding variant, rs7934606 in MUC2 was significant among German patients [2.85 (5.05-1.60); 4.03 × 10-4] and combined European IPF cases [2.18 (3.16-1.50); 3.73 × 10-5]. The network analysis for these variants indicated gene-gene and gene-phenotype interactions in IPF and lung biology. With replication of MUC5B rs35705950 previously reported in U.S. populations of European descent and indicating other plausible polymorphic variants relevant for IPF, we provide additional reference information for future extended functional and population studies aimed, ideally with inclusion of clinical parameters, at identification of IPF genetic markers. © 2016 Kishore, Žižková, Kocourková, Petrkova, Bouros, Nunes, Loštáková, Müller-Quernheim, Zissel, Kolek, Bouros,Valeyre and Petrek.

Colchicine is an antimitotic drug which binds to tubulin and at high doses results in cytoskeleton disruption. Colchicine is believed to be an anti-inflammatory agent, though its modulatory effects on the level and transcriptional activity of genes is still a matter of debate. There is growing evidence that alterations in the cytoskeleton exert specific effects on the expression of various genes. This study was undertaken to analyze whether disrupting the microtubule cytoskeleton by colchicine modulates transcriptional levels of MEFV, NF-κB p65, NLRP3, HMGB1, and caspase-3 in neutrophils from patients with familial Mediterranean fever (FMF) and healthy subjects. In the present study, colchicine caused increased expression of NLRP3 (p=0.007) and MEFV (p=0.03), but had no effect on caspase-3, NF-κB p65 and HMGB1 genes in healthy neutrophils. FMF neutrophils were less responsive to the drug treatment. This study supports the hypothesis that, being an anti-inflammatory agent, colchicine at relatively high concentrations might lead to the activation of pro-inflammatory signalling pathways in neutrophils.

Immunobiological activity of the polybacterial lysate Olimunostim (P. acnes, K. pneumoniae, S. aureus) was examined by investigating its effects on murine lymphocytes. When added to in vitro lymphocyte cultures, Olimunostim induced interleukin-2 (IL-2) biological activity (in a 2-d culture) and subsequently potentiated lymphocyte proliferation (on day 3); the latter effect was dependent on the presence of adherent cells. In vivo, significant enhancement of lymphocyte reactivity to T-mitogens and increase of CD4+ helper-inducer T lymphocytes were observed 3 d after a subcutaneous application of Olimunostim to mice with cellular immune deficiency. These results confirm the modulatory properties of Olimunostim towards lymphocytes both in vitro and in vivo, which may form a basis for its clinical application.

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