An effective cytotoxic immune response to neoplastic cells requires efficient presentation of antigenic peptides to T lymphocytes by HLA class I (HLA-I) molecules. The HLA-I-bound peptide repertoire depends on antigen-processing machinery molecules. Aminopeptidase residing in endoplasmic reticulum 1 (ERAP1) trims peptides to the optimal length for HLA-I binding. Single nucleotide polymorphisms (SNPs) in the ERAP1 gene result in changes in aminopeptidase activity and specificity. This may affect susceptibility to cancer. However, non-small cell lung carcinoma (NSCLC) has not been studied in this respect. We compared genotype and haplotype frequencies of four coding, nonsynonymous ERAP1 SNPs, rs26653G > C, rs26618T > C, rs30187C > T, and rs27044C > G, in NSCLC occurring in two genetically distant populations, Chinese and Poles. We found associations of all four SNPs with NSCLC in Chinese but not in Poles. The differences in ERAP1-NSCLC associations might be explained by highly significant differences in SNP genotype frequencies between Chinese and Poles (except for rs26618). In accordance with this, the most frequent ERAP1 haplotypes were distributed differently in cases versus controls in Chinese, but not in Poles. Our findings add to the differences between Orientals and Caucasians in genetics of disease susceptibility.Electronic supplementary materialThe online version of this article (doi:10.1007/s00005-016-0436-4) contains supplementary material, which is available to authorized users.

Lung cancer is strongly associated with cigarette smoking; nevertheless some never-smokers develop cancer. Immune eradication of cancer cells is dependent on polymorphisms of HLA class I molecules and antigen-processing machinery (APM) components. We have already published highly significant associations of single nucleotide polymorphisms (SNPs) of the ERAP1 gene with non-small cell lung cancer (NSCLC) in Chinese, but not in Polish populations. However, the smoking status of participants was not known in the previous study. Here, we compared the distribution of APM polymorphic variants in larger cohorts of Polish patients with NSCLC and controls, stratified according to their smoking status. We found significant but opposite associations in never-smokers and in smokers of all tested SNPs (rs26653, rs2287987, rs30187, and rs27044) but one (rs26618) in ERAP1. No significant associations were seen in other genes. Haplotype analysis indicated that the distribution of many ERAP1/2 haplotypes is opposite, depending on smoking status. Additionally, haplotypic combination of low activity ERAP1 and the lack of an active form of ERAP2 seems to favor the disease in never-smokers. We also revealed interesting associations of some APM polymorphisms with: age at diagnosis (ERAP1 rs26653), disease stage (ERAP1 rs27044, PSMB9 rs17587), overall survival (ERAP1 rs30187), and response to chemotherapy (ERAP1 rs27044). The results presented here may suggest the important role for ERAP1 in the anti-cancer response, which is different in smokers versus never-smokers, depending to some extent on the presence of ERAP2, and affecting NSCLC clinical course.

Surgical and endovascular revascularization of ischemic legs in patients with peripheral arterial disease (PAD) can damage the arterial wall (endothelial and smooth muscle cells). Hemostatic factors released during endothelial dysfunction can lead to restenosis. 1. Determination of selected endothelial hemostatic factors in PAD patients and a reference group. 2. Prospective observation of new restenosis appearance in PAD patients after endovascular revascularization. 3. Comparison of selected endothelial hemostatic factors between non-restenotic and restenotic PAD patients. 150 PAD patients after endovascular revascularization - 90 men and 60 women, aged 44-88 (mean 65.5) years - were examined. During one-year observation after the revascularization procedures in 38 PAD patients restenosis occurred, when blood samples were also collected. The reference group consisted of 53 healthy persons - 44 men and 9 women, aged 20-56 years. Blood was drawn in the morning into 3.2% sodium citrate at a ratio of 9:1. Tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA) were measured in plasma with commercial tests using the enzyme immunoassay. In the plasma of PAD patients after revascularization, the concentrations of TF and vWF were significantly higher, TM lower, TFPI and t-PA similar compared to the reference group. Six months after revascularization the level of TF had increased and vWF had significantly decreased. The endothelial hemostatic factors before and after restenosis did not significantly differ except TF, which after restenosis was higher. Increased TF and vWF levels in PAD patients indicate arterial endothelial cell damage, by atherosclerotic and revascularization processes. In PAD patients with restenosis compared to these patients before restenosis the determined endothelial hemostatic factors, except TF level, did not significantly differ. Perhaps TF participates in restenosis formation.

Background. Alopecia areata (AA) is the second most common cause of non-scarring alopecia. Little is known on the etiopathogenesis of AA. It is considered an autoimmune disease, with T lymphocytes and antibodies directed against hair follicle structures. Topical and systemic therapies are used for the treatment of AA, but none of the therapies used to date have a permanent therapeutic effect.Objectives. To evaluate the efficacy and safety of AA treatment through a single intradermal injection of a suspension of allogeneic MSCs extracted from Wharton's jelly (WJ-MSCs) into the alopecia foci. Materials and methods.The study involved 4 AA patients who underwent experimental therapy with a suspension of WJ-MSCs. The AA intensity was measured using the SALT score. This measure was performed 3 times during treatment: 1 st measure (SALT 0 ) prior to treatment; 2 nd measure (SALT 12 ) 12 weeks after the treatment; and 3 rd measure (SALT 24 ) 24 weeks after the treatment. Furthermore, during each follow-up visit (6, 12, 18, and 24 weeks after the administration of WJ-MSCs) the patient's general condition (physical examination) and local condition were assessed, their mood was evaluated, and a photo of the scalp was taken.Results. Hair regrowth was observed in all patients by an average of 67% at the sites where the cell suspension was administered. In all cases, we observed greater dynamics of hair regrowth in the first 3 months after the treatment, with an average increase of 52.2%, compared to the following 3 months, with an average of 32%.Conclusions. The results of the applied intradermal injections of an allogeneic WJ-MSC suspension were positive with hair growth observed in all participants and the therapy was found to be safe, with no side effects.

Patients with abdominal aortic aneurysm (AAA) experience impaired balance between fibrinolysis and coagulation, manifested by increased prothrombotic tendency and intensified inflammatory processes. The aim of this study was to evaluate the TAFI activity level (thrombin activatable fibrinolysis inhibitor) in the plasma of AAA patients. Plasma levels of PAI-1 (plasminogen activator inhibitor type 1), urokinase-type plasminogen activator and uPAR (urokinase-type plasminogen activator receptor) were measured as markers of fibrinolytic activity. The study showed that the activity of the thrombin-activatable fibrinolysis inhibitor in the plasma of AAA patients was significantly lower than in the plasma of the control individuals (64.6 ± 10.1 vs. 54.2 ± 10.9%, P < 0.0001). TAFI activity positively correlated with the white blood cell count (r = 0.486, P < 0.005). The uPAR concentration in the AAA patients was statistically significantly higher than in the control group and positively correlated with TAFI activity (r = 0.409, P = 0.02). The levels of PAI-1 and D-dimers (fibrin fragments) were significantly higher in patients with AAA than in the control group (44.3 ± 17.5 vs. 21.7 ± 8.7 ng/ml and 1869.6 ± 1490.1 vs. 181.5 ± 188.6 ng/ml, respectively). Lowered activity of the fibrinolysis inhibitor TAFI may heighten the blood fibrinolytic potential in AAA patients and contribute to the development of comorbidities. Therefore, TAFI participation in AAA pathogenesis cannot be excluded.