CTLA‐4 (CD152) enhances the Tc17 differentiation program

Although CD8⁺ T cells that produce IL‐17 (Tc17 cells) have been linked to host defense, Tc17 cells show reduced cytotoxic activity, which is the characteristic function of CD8⁺ T cells. Here, we show that CTLA‐4 enhances the frequency of IL‐17 in CD8⁺ T cells, indicating that CTLA‐4 (CD152) specifically promotes Tc17 differentiation. Simultaneous stimulation of CTLA‐4^+/+ and CTLA‐4^?/? T cells in cocultures and agonistic CTLA‐4 stimulation unambiguously revealed a cell‐intrinsic mechanism for IL‐17 control by CTLA‐4. The quality of CTLA‐4‐induced Tc17 cells was tested in vivo, utilizing infection with the facultative intracellular bacterium Listeria monocytogenes (LM). Unlike CTLA‐4^+/+ Tc17 cells, CTLA‐4^?/? were nearly as efficient as Tc1 CTLA‐4^+/+ cells in LM clearance. Additionally, adoptively transferred CTLA‐4^?/? Tc17 cells expressed granzyme B after rechallenge, and produced Tc1 cytokines such as IFN‐γ and TNF‐α, which strongly correlate with bacterial clearance. CTLA‐4^+/+ Tc17 cells demonstrated a high‐quality Tc17 differentiation program ex vivo, which was also evident in isolated IL‐17‐secreting Tc17 cells, with CTLA‐4‐mediated enhanced upregulation of Tc17‐related molecules such as IL‐17A, RORγt, and IRF‐4. Our results show that CTLA‐4 promotes Tc17 differentiation that results in robust Tc17 responses. Its inactivation might therefore represent a central therapeutic target to enhance clearance of infection.     

Superiority of measuring apolipoprotein B to conventional lipid profile predicting risk of acute coronary syndrome in young people

The purpose of this study is to compare the importance and its superiority of apolipoprotein B (apoB) over conventional lipid profile for predicting risk of acute coronary syndrome in young people of Bangladesh. This case-control study was carried out in Department of Cardiology, of Mymensingh Medical College Hospital within the period from June 2009 to May 2010. A total 50 case of 18-45 years of age with first attack of acute coronary syndrome admitted in coronary care unit and 50 healthy controls of same age and sex distribution were studied. Twenty five (50.0%) of the studied case had hyper apoB condition, those low density lipoprotein cholesterol (LDL-C) level was normal, thus conventional lipid profile underestimated the risk. Among the controls 23(46.0%) with high LDL-C had hyper apoB condition. Hyper-ApoB in these controls may cause acute coronary syndrome in future. The present study shows significant association of apolipoprotein B as an independent determinant and estimation of apoB other than conventional lipid profile may be an alternative tool for predicting risk of development of acute coronary syndrome in young people.     

Influence of glycosylated hemoglobin on sight-threatening diabetic retinopathy: a population-based study

Aim

To evaluate the role of glycosylated hemoglobin (HbA1c) on the occurrence of sight-threatening diabetic retinopathy (STDR) in urban Chennai, Tamil Nadu, India.

Methods

A total of 5999 individuals were enumerated from the Chennai metropolis. Of these, 1414 subjects with diabetes were included for data analysis in the study. STDR or non-STDR groups were classified based on the fundus photographs. HbA1c was measured (Bio-Rad DiaSTAT™ HbA1c Reagent Kit) by the liquid chromatography technique.

Results

A statistically significant difference (p < 0.05) was noted in the duration of diabetes, gender, body mass index, HbA1c, micro- and macro-albuminuria between both non-STDR and STDR groups as compared to the no-diabetic retinopathy (DR) group. On multivariate analysis, HbA1c (non-STDR: odd's ratio OR = 1.23; 95% confidence interval CI = 1.15-1.32; p < 0.0001; STDR: OR = 1.31 95% CI = 1.14-1.52; p < 0.0001) was found to be significantly associated with non-STDR and STDR when compared with the no-DR group. The Receiver Operating Characteristic analysis showed that the cut-off value of 8.0 had 75.6% sensitivity and 58.2% specificity with 64.9% maximum area under the curve.

Conclusion

HbA1c value >8.0% was significantly related with STDR. In a screening programme, the cut-off value of HbA1c >8.0% provided a maximum yield of STDR.     

The development and evaluation of a single step multiplex PCR method for simultaneous detection of Brugia malayi and Wuchereria bancrofti

A single step novel multiplex polymerase chain reaction (PCR) has been developed for simultaneous detection of human filarial parasites, Brugia malayi and Wuchereria bancrofti, from blood samples and mosquitoes. The primers used were novel and have been tested with the parasite DNA amplifying 188bp (BM) and 129bp (WB) DNA fragments, specific to B. malayi and W. bancrofti, respectively, in a single reaction. The specificity of the PCR product was confirmed by DNA sequencing and slot blot hybridization assay. The test was found highly sensitive for both B. malayi and W. bancrofti by detecting the parasitaemia up to the level of one microfilaria per reaction. The assay was further evaluated on 98 blood samples and 144 mosquito samples collected from filarial endemic areas. The PCR was found to be more efficient in comparison to microscopy by detecting 8% and 5% more filarial parasites in field-collected blood and mosquito samples, respectively. This novel PCR that offers scope for simultaneous detection of both the parasites may be used as a diagnostic tool for the detection of filariasis in population and can be adopted for rapid surveillance and monitoring of mosquitoes for use in the effective control of filariasis.