Swept Source OCT dans le suivi d’une effusion uvéale posttrabéculectomie chez une patiente nanophtalme

Uveal effusion syndrome describes serous detachments of the choroid and ciliary body with exudative retinal detachment. It is a complication following glaucoma filtering surgeries such as trabeculectomy especially in nanophthalmic eyes.We report a rare case of a 42-year-old-woman, with nanophtalmos, who developed posterior serous retinal detachment and uveal effusions after trabeculectomy for chronic angle closure glaucoma.The patient was put on oral steroids with good clinical outcome. Anterior Segment OCT allowed monitoring of iridocorneal angle and anterior chamber depth, Swept Source OCT was useful for monitoring retinal reattachment and choroidal thickness.     

Chromosomal segregation in spermatozoa of five Robertsonian translocation carriers t(13;14)

Purpose  

To analyse the segregation of a Robertsonian translocation t(13;14) in five male carriers, and to verify a possible inter-chromosomal effect (ICE) of the Robertsonian translocation on chromosomes 18, X, and Y.     

Rapid detection of Candida albicans in clinical blood samples by using a TaqMan-based PCR assay

We describe a rapid and reproducible PCR assay for quantitation of the Candida albicans ribosomal DNA (rDNA) in clinical blood samples based on the TaqMan principle (Applied Biosystems), in which a signal is generated by cleavage of a template-specific probe during amplification. We used two fluorogenic probes based on universal, fungus-specific primers, one for the detection of C. albicans species DNA and one for the detection of all Candida genus DNA. C. albicans blastoconidia mixed with whole blood in a titration experiment yielded a linear PCR signal over a range of 3 orders of magnitude. The TaqMan-based PCR assay for C. albicans exhibited a low limit of detection (5 CFU/ml of blood) and an excellent reproducibility (96 to 99%). While the C. albicans species-specific probe had 100% specificity for C. albicans, all Candida genus-specific probes cross-reacted with other organisms likely to coinfect patients with C. albicans infections. On the basis of these data, we determined the C. albicans loads with a species-specific probe from 122 blood samples from 61 hematology or oncology patients with clinically proven or suspected systemic Candida infections. Eleven positive samples exhibited a wide range of C. albicans loads, extending from 5 to 100,475 CFU/ml of blood. The sensitivity and specificity of the present assay were 100 and 97%, respectively, compared with the results of blood culture. These data indicate that the TaqMan-based PCR assay for quantitation of C. albicans with a species-specific probe provides an attractive alternative for the identification and quantitation of C. albicans rDNA in pure cultures and blood samples.     

Disease etiology and diagnosis by TCR repertoire analysis goes viral

The importance of T‐cell receptor (TCR) repertoire diversity is highlighted in murine models of immunodeficiency and in many human pathologies. However, the true extent of TCR diversity and how this diversity varies in health and disease is poorly understood. In a previous issue of the European Journal of Immunology, Lossius et al. [Eur. J. Immunol. 2014. 44: 3439–3452] dissected the composition of the TCR repertoire in the context of multiple sclerosis (MS) using high‐throughput sequencing of TCR‐β chains in cerebrospinal fluid samples and blood. The authors demonstrated that the TCR repertoire of the CSF was largely distinct from the blood and enriched in EBV‐reactive CD8⁺ T cells in MS patients. Studies of this kind have long been hindered by technical limitations and remain scarce in the literature. However, TCR sequencing methodologies are progressing apace and will undoubtedly shed light on the genetic basis of T‐cell responses and the ontogeny of T‐cell‐mediated diseases, such as MS.     

Ⅰ型干扰素参与调节SLE外周T细胞活化和TLR表达谱的研究

血清高水平Ⅰ型干扰素(typeⅠinterferon)是系统性红斑狼疮(SLE)患者重要的病理特征之一,外周高水平IFN-α对T细胞的免疫调节作用值得深入探讨。本研究首先比较分析了SLE患者外周血T细胞活化和TLR分子表达格局,结果显示SLE患者外周血CD4~+或CD8~+T细胞和正常人相比呈现出更加活化的表型变化,其表面活化标志CD69和HLA-DR表达阳性率均高于正常人;分析T细胞表达TLR分子格局发现,SLE患者较正常人T细胞中TLR分子的表达有明显升高,其中CD4~+T细胞中TLR8和TLR9的升高明显,而在CD8~+T细胞中明显升高的TLR分子有TLR3和TLR8;结合SLE病理状态下外周高水平IFN-α的持续存在,我们进一步分析了IFN-α对正常T细胞活化和TLR分子表达谱的影响,结果显示IFN-α协同TCR信号可以促进T细胞的活化,并上调T细胞中部分TLR分子的表达,其中CD4~+和CD8~+T细胞中TLR8的表达均明显上升。综合分析SLE患者和经IFN-α活化的正常T细胞的活化和TLR分子表达谱的变化格局,提示SLE病理状态下高水平的Ⅰ型干扰素可以与T细胞的持续活化有关,其对T细胞表达TLR分子格局的影响,特别是与核酸类分子配体相关的TLR分子的表达增高为内源性核酸类配体参与T细胞的活化提供了分子基础。     

Microenvironmental hypoxia orchestrating the cell stroma cross talk, tumor progression and antitumor response

Hypoxia, a common feature of solid tumors and one of the hallmarks of tumor microenvironment, favors tumor survival and progression. Although hypoxia has been reported to play a major role in the acquisition of tumor resistance to cell death, the molecular mechanisms that control the survival of hypoxic cancer cells and the role of hypoxic stress in shaping the cross talk between immune cells and stroma components are not fully elucidated. Recently, several lines of investigation are pointing to yet another ominous outcome of hypoxia in the tumor microenvironment involving suppression of antitumor immune effector cells and enhancement of tumor escape from immune surveillance. Although the identification of tumor-associated antigens provided a new arsenal of approaches to enhance antigen-specific response, the immunotherapy approaches that are currently used in the clinic have only limited success. In fact, tumor stroma components including hypoxia are engaged in an active molecular cross talk that has serious implications for immunological recognition of tumor in shaping the microenvironment. In this review, we will focus on the impact of hypoxia on the regulation of the antitumor response and the subsequent tumor progression. We will also in particular discuss data that indicate that manipulation of hypoxic stress may represent an innovative strategy for a better immunotherapy of cancer.     

Functional characterization of naturally occurring genetic variants in the human TLR1-2-6 gene family

Toll-like receptors (TLRs) are considered an essential component of the innate immune system, initiating inflammatory responses following infection of the host. Humans have 10 functional TLRs, differing in their subcellular distributions and the microbial agonists they sense. The phylogenetically conserved TLR1-2-6 family is unique in that TLR1 and TLR6 form heterodimers with TLR2 to mediate signalling in response to agonists. Epidemiological genetic studies have identified several TLR variants that appear to influence susceptibility to infectious diseases, but the functional consequences of which remain largely unknown. Here, we assessed the functional impact of the TLR1-2-6 variants with altered amino acid sequences segregating naturally in the human population. We used an NF-κB reporter assay in TLR-transfected human embryonic kidney 293T cells stimulated with the corresponding TLR agonists. We found that among the 41 naturally occurring variants with amino acid alterations identified in the TLR1-2-6 family, 14 of them (five TLR1, four TLR2, and five TLR6 variants) displayed marked impairment of NF-κB activation. Most of these variants are present at very low population frequencies and are population-specific. These observations suggest that rare, nonsynonymous TLR mutations are likely to have deleterious effects on immune responses and may therefore contribute to complex susceptibility to infection at the population level.     

Effect of donor CTLA-4 alleles and haplotypes on graft-versus-host disease occurrence in Tunisian patients receiving a human leukocyte antigen-identical sibling hematopoietic stem cell transplant

The CTLA-4 genetic variation, such as single nucleotide polymorphisms (SNPs) may be critical and can affect the functional activity of cells that initiate the graft-versus-host disease (GVHD) effects. The aim of this study is to examine the effect of donor CTLA-4 alleles and haplotypes for the -318C>T and the 49A>G polymorphisms on the occurrence of GVHD in Tunisians recipients of HSCs. A total of 112 patients and their 112 respective sibling donors of HSCs were enrolled in this study. All patients had either grades 0-I or grades II-IV acute GVHD, or chronic GVHD. The SNPs genotyping assay was performed using sets of sequence specific primers (SSP-PCR). The single marker association analysis showed that the 49G allele, in a genetic recessive model, may be a potential risk factor only for the chronic GVHD (p = 0.032, odds ratio [OR] = 2.58, 95% confidence interval = 1.05-6.32). The haplotypes analyses showed that the CTLA-4 -318C49G nucleotide combination is significantly associated with the incidence of chronic GVHD (p = 0.043, χ2 = 3.27). Donor CTLA-4 -318C49G haplotype may be a significant risk factor for developing chronic GVHD after allo-stem cell transplantation. We suppose that donor T cells expressing this haplotype in a homozygous state have higher proliferation than those expressing other haplotypes, especially after recognition of the recipient's minor histocompatibility antigens.