Interleukin-6 blood levels in sensitive and multiresistant tuberculosis.

BACKGROUND: Interleukin-6 (IL-6) is a proinflammatory cytokine implicated in the immunopathogenesis of tuberculosis (TB). Multidrug resistance in tuberculosis is recognized worldwide as an important public health issue. The mechanism underlying TB pathogenesis in general and drug resistance in particular is not well understood, but it may be that IL-6 is one factor that enhances pathology in drug-resistant TB. The purpose of this study was to identify patterns of IL-6 production in active pulmonary TB with different sensitivity to standard drug therapy. PATIENTS AND METHODS: IL-6 blood levels were studied in 38 patients with active pulmonary TB: 23 patients were very sensitive to specific chemotherapy (STB), and 15 were multiresistant (MDRTB). An ELISA assay (Biossource) was used to quantify IL-6 in the sera of 38 TB patients and 63 healthy blood donors. RESULTS: The STB group was composed of 16 males (73.9%) and 7 females, MDRTB by 9 males (60%) and 6 females, and control group by 51 males (81%) and 12 females. The results showed a significant increase in IL-6 concentration in TB (median = 4.3 pg/ml, range 0.5-24) compared to that of healthy individuals (median = 0.5 pg/ml, range 0-2.8, p < 0.001). Additionally, IL-6 concentrations were increased in both STB (median = 4.1 pg/ml, range 0.5-24) and MDRTB (median = 5.1 pg/ml, range 0.5-12) groups in relation to controls (p < 0.001). In contrast, significant differences were not observed between STB and MDRTB groups (p > 0.05). CONCLUSION: IL-6 levels were increased in pulmonary tuberculosis, independent of drug resistance.

Semen quality is affected by HLA class I alleles together with sexually transmitted diseases.

BACKGROUND: The human leukocyte antigen (HLA) locus includes several genes with key roles in antigen presentation and immune response, some of them inclusively found to be associated with non-obstructive azoospermia. Still, HLA connections to other infertility phenotypes such as semen hyperviscosity (SHV), asthenozoospermia (AST), and oligozoospermia (OLI) have been often neglected. OBJECTIVES: In this work, we aimed to evaluate the association of HLA class I and II genes with SHV, AST, and OLI phenotypes while exploring a possible role in an adaptive immune response to sexually transmitted diseases (STD). MATERIALS AND METHODS: Whole-exome sequencing was performed in a Portuguese cohort of 71 infertility cases and 68 controls, followed by HLA typing using a specific software-HLA*PRG:LA tool. Molecular screenings of seven STD were carried out in a subset of 72 samples (30 cases and 42 controls). RESULTS: Statistical tests uncovered three protective alleles: HLA-A*11:01, associated with all forms of male infertility (p = 0.0006); HLA-DQB1*03:02 with SHV and OLI (PSHV  = 0.0303, POLI  = 0.0153); and HLA-A*29:02 with OLI (p = 0.0355), which was found to interfere in sperm number together with HPV (p = 0.0313). Five risk alleles were also identified: two linked with SHV (HLA-B*50:01, p = 0.0278; and HLA-C*06:02, p = 0.0461), another one with both SHV and OLI (HLA-DQA1*05:01, PSHV  = 0.0444 and POLI =0.0265), and two with OLI (HLA-C*03:03, p = 0.0480; and HLA-DQB1*03:01, p = 0.0499). Here, HLA-C*03:03 carriers tend to be HPV infected. CONCLUSIONS: The application of HLA*PRG:LA tool to the study of male infertility provided novel insights for an HLA correlation with semen quality, namely among SHV and OLI phenotypes. The discovery of an HLA-A*29:02/HPV crosstalk, together with former reports of HLA alleles conferring resistance-susceptibility to diverse human pathogens, raises the hypothesis of a mechanistic link between male infertility, HLA polymorphism, and host response to STD.

GLUT1, MCT1/4 and CD147 overexpression supports the metabolic reprogramming in papillary renal cell carcinoma.

Papillary Renal Cell carcinoma (pRCC) is the second most common type of RCC, accounting for about 15% of all RCCs. Surgical excision is the main treatment option. Still, 10 - 15 % of clinically localized tumours will recur and/or develop metastasis early after surgery, and no reliable prognostic biomarkers are available to identify them. It is known that pRCC cells rely on high rates of aerobic glycolysis, characterized by the up-regulation of many proteins and enzymes related with the glycolytic pathway. However, a metabolic signature enabling the identification of advanced pRCC tumours remains to be discovered. The aim of this study was to characterize the metabolic phenotype of pRCCs (subtypes 1-pRCC1 and 2-pRCC2) by evaluating the expression pattern of the glucose transporters (GLUTs) 1 and 4 and the monocarboxylate transporters (MCTs) 1 and 4, as well as their chaperon CD147. We analysed the clinico-pathological data and the protein and mRNA expression of GLUT1, GLUT4 and MCT1, MCT4 and CD147 in tumours from Porto and TCGA series (http://cancergenome.nih.gov/), respectively. With the exception of GLUT4, plasma membrane expression of all proteins was frequently observed in pRCCs. GLUT1 and MCT1 membrane overexpression was significantly higher in pRCC2 and significantly associated with higher pN-stage and higher Fuhrman grade. Overexpression of GLUT1, MCT1/4 and CD147, supports the metabolic reprograming in pRCCs. MCT1 expression was associated with pRCC aggressiveness, regardless of the tumour histotype.