CD4+ T cells and natural killer cells: Biomarkers for hepatic fibrosis in human immunodeficiency virus/hepatitis C virus-coinfected patients

AIM To characterize peripheral blood natural killer(NK) cells phenotypes by flow cytometry as potential biomarker of liver fibrosis in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients.METHODS Peripheral mononuclear cells from 24 HIV/HCV(HBVnegative) coinfected and 5 HIV/HCV/HBV seronegative individuals were evaluated. HIV/HCV coinfected patients were divided in to groups: G1, patients with METAVIR F0-F2 and G2, patients with METAVIR F3-F4. NK surface cell staining was performed with: AntiCD3(APC/Cy7), anti-CD56(PE/Cy5), anti-CD57(APC), anti-CD25(PE), anti-CD69(FITC), anti-NKp30(PE), antiNKp46(PE/Cy7), anti-NKG2D(APC), anti-DNAM(FITC); anti-CD62L(PE/Cy7), anti-CCR7(PE), anti-TRAIL(PE), anti-Fas L(PE), anti CD94(FITC). Flow cytometry data acquisition was performed on BD FACSCanto, analyzed using Flow Jo software. Frequency of fluorescence was analyzed for all single markers. Clinical records were reviewed, and epidemiological and clinical data were obtained.RESULTS Samples from 11 patients were included in G1 and from 13 in G2. All patients were on ARV, with undetectable HIV viral load. Liver fibrosis was evaluated by transient elastography in 90% of the patients and with biopsy in 10% of the patients. Mean HCV viral load was(6.18 ± 0.7 log10). Even though, no major significant differences were observed between G1 and G2 regarding NK surface markers, it was found that patients with higher liver fibrosis presented statistically lower percentage of NK cells than individual with low to mild fibrosis and healthy controls(G2: 5.4% ± 2.3%, G1: 12.6% ± 8.2%, P = 0.002 and healthy controls 12.2% ± 2.7%, P = 0.008). It was also found that individuals with higher liver fibrosis presented lower CD4 LT count than those from G1(G2: 521 ± 312 cells/μL, G1: 770 ± 205 cells/μL; P = 0.035).CONCLUSION Higher levels of liver fibrosis were associated with lower percentage of NK cells and LTCD4+ count; and they may serve as noninvasive biomarkers of liver damage.

X-linked Toll-like receptor 7 polymorphism associated with susceptibility to Chikungunya Fever

Objective: To investigate the association between TLR3 and TLR7 polymorphisms with susceptibility and clinical manifestations of Chikungunya Fever.Methods: A total of 177 individuals were studied: 73 patients with a confirmed diagnosis for Chikungunya virus and 104 non-infected individuals. Polymorphisms were determined by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP).Results: Our analysis showed an increased CC genotype frequency of the TLR7 rs3853839 polymorphism in male patients compared to control(29% versus 2%,respectively; OR=20.69; 95% CI=2.55-167.36; P<0.001). Furthermore,arthritis(acute and chronic) was frequently found in CC male patients. On the contrary,65% of CG carriers were no-infected males(29% versus 65%,respectively; OR=0.23,95% CI=0.48-3.04; P=0.002). Finally,we observed a higher frequency of lymphopenia in CG male patients(CG=666.86±233.77,GG=1,314.27±752.29 cells/mm3,P=0.047). Conclusions: Our results suggest the TLR7 rs3853839 polymorphism is associated with lymphopenia and increased susceptibility to Chikungunya Fever in males.

Daily expression of sodium-dependent glucose cotransporter-1protein in jejunum during rat ontogeny

It is widely known that intestinal capacities such as the enzymatic hydrolysis of carbohydrates,lipids and proteins,and the subsequent absorption of the hydrolyzed products.are evolutionary matched to dietary loads and feeding behaviors.In this study,we demonstrate that the protein expression of apically located sodium-dependent glucose cotransporter-1(SGLT-1)throughout rat ontogeny is daily adjusted to afford glucose uptake when the load of this metabolically essential monosaccharide in the intestinal lumen is maximum.The jejunal expression of SGLT-1 protein in 14 one-day-old suckling pups was found to increase at dark and early light phase(P<0.05).when they have a better access to mother milk.In weaning21-d-old and juvenile 28-d-old rats,the cotransporter expression was high throughout the entire day(P<0.05).Finally,adult 90-d-old rats showed a well-developed circadian rhythm for SGLT-1 protein(P<0.05).whose expression increased at late light and dark phase when the highest intestinal glucose load was achieved.To our knowledge,these results are the first reporting the daily profile of SGLT-1 expression during rat early developmental stage and may contribute to understand the biological significance of a well-established molecular capacity to deal with the crucial increase of glucose load in the diet during the weaning process.