Immunosenescence in rheumatoid arthritis: Use of CD28 negative T cells to predict treatment response

Not many years ago achieving remission in rheumatoid arthritis (RA) was difficult due to lack of effective treatment. With the advent of biologics, remission is very much within reach. But biologics are expensive. And not all patients respond adequately to biologics. Hence it will be useful if we have a marker which predicts response to any disease modifying anti-rheumatic drug (DMARD), whether conventional or biologic. Expansion of CD28-ve T cells is characteristically seen in RA. Both CD28-ve T Cells and RA are believed to be linked to immunosenescence. The available evidence is suggestive of an intimate relationship between RA and clonal expansion of CD28-ve T cells. Newer biomarkers are constantly being looked at and CD28-ve T cells is one of them. In this review the relationship between immune disorders like RA and immunosenescence and significance of CD28-ve T cells in RA is discussed.     

MicroRNA-Mediated Restriction of HIV-1 in Resting CD4+ T Cells and Monocytes

In contrast to activated CD4⁺ T cells and differentiated macrophages, resting CD4⁺ T cells and monocytes are non-permissive for HIV-1 replication. The mediators which regulate the resting or quiescent phenotype are often actively involved in the restriction of viral replication and the establishment and maintenance of viral latency. Recently, certain microRNAs which are highly expressed in resting cells have been implicated in this capacity, inhibiting the expression of cellular proteins that are also viral co-factors; following activation these microRNAs exhibit decreased expression, while their targets are correspondingly up-regulated, contributing to a favorable milieu for virus replication. Other microRNAs exhibiting a similar expression pattern in resting and activated cells have been shown to directly target the HIV-1 genome. In this review we will discuss the resting state and the causes behind viral restriction in resting cells, with emphasis on the role of microRNAs.     

Activity of CD101, a long-acting echinocandin,against clinical isolates of Candida auris

CD101 is a new echinocandin with a prolonged half-life. CD101 was tested by broth microdilution against 100 isolates of the emerging yeast Candida auris. It showed activity against most isolates, including some that were resistant to other echinocandins.     

A Clinical Update of the Hb Siirt [β27(B9)Ala→Gly; HBB: c.83C>G] Hemoglobin Variant

We report a clinical update of the hemoglobin (Hb) variant [β27(B9)Ala→Gly; HBB: c.83C>G], named Hb Siirt, that was previously described as a silent variant in a 23-year-old Kurdish female. The patient was also a carrier of the codon 5 (–CT) (HBB: c.17_18delCT) frameshift mutation and of the ααα ^{anti 3.7} triplication. Her initial moderate β-thalassemia intermedia (β-TI) phenotype worsened with time, causing the patient to become a transfusion-dependent subject at the age of ～40 years. Subsequent molecular characterization of both parents revealed that the Hb Siirt variant was inherited by the mother, while the other two globin alterations (HBB: c.17_18delCT and ααα^{anti 3.7} triplication) were genetically transmitted by the father. The latter remained a carrier of a mild β-TI phenotype throughout his life, at least until the age of 65 years. We hypothesize that the worsened clinical conditions in the daughter were due to the additional, maternally inherited Hb Siirt variant. However, protein 3D conformational analysis did not seem to reveal substantial overall structural changes. Among the other three described variants [Hb Volga (HBB: c.83C>A), Hb Knossos (HBB: c.82?G>T), Hb Grange-Blanche (HBB: c.83C>T] that are due to nucleotide substitutions at codon 27 of the β-globin gene; only Hb Knossos causes a β⁺-thalassemia (β⁺-thal) phenotype.     

Loss of CD7, independent of galectin-3 expression, implies a worse prognosis in adult T-cell leukaemia/lymphoma

Aims:  Loss of CD7 is characteristic of adult T-cell lymphoma/leukaemia (ATLL). Galectin-3 (Gal-3) is strongly induced in cultured human T lymphotropic virus-1-infected T lymphocytes, and may cause apoptosis through interaction with CD7. The aim was to investigate the clinical relevance of the Gal-3–CD7 pathway in ATLL.
Methods and results:  Immunohistochemistry for Gal-3 and CD7 was performed on 22 cases of ATLL in the leukaemic phase. We found that the lymphoma cells were not necessarily Gal-3+, but Gal-3+ stromal cells could always be found. Independent of the status of Gal-3, there was an association of loss of CD7 with a worse prognosis.
Conclusions:  These data suggest that, by down-regulating CD7, ATLL cells could have escaped Gal-3-induced apoptosis to run a more aggressive clinical course.     

老年卵巢癌组织中转移抑制基因MRP-1/CD9与integrinsα5的表达特性

目的探讨MRP-1/CD9和integrinsα5在老年卵巢癌浸润、转移发生中的作用及二者的相关性。方法应用RT-PCR方法检测正常卵巢组织(Ⅰ组)、卵巢良性肿瘤组织(Ⅱ组)、卵巢交界性瘤组织(Ⅲ组)和卵巢癌组织(Ⅳ组)中MRP-1/CD9及整合素的mRNA水平表达,统计学多因素分析MRP-1/CD9和integrinsα5基因的表达及与患者年龄、组织分化、淋巴转移、TNM分期及病理分型等的相关性。结果MRP-1/CD9和integrinsα5在卵巢癌组织中存在和生物学的作用确切。卵巢癌组各基因表达在肿瘤晚期年龄比较有显著差异;在组织分化程度上,高、中分化程度肿瘤的表达与低分化比较有显著性差异,而高、中分化间无明显差异;在卵巢癌组(Ⅲ、Ⅳ期)中存在明显的表达减弱,与良性肿瘤组、交界性肿瘤组及卵巢癌组早期比较有显著的差异;其表达在无淋巴转移和有淋巴转移方面有显著性差异,无淋巴转移者出现高表达。结论MRP-1/CD9与integrinsα5基因在晚期卵巢癌中,年龄比较存在差异,老年性卵巢癌基因缺失表达下降,提示老年肿瘤发生浸润、转移能力降低,对判断肿瘤的预后、制定肿瘤的治疗方案具有重要意义。     

The changing demographics of new HIV diagnoses at a London centre from 1994 to 2000

Objective

To document the demographic changes in new HIV diagnoses at the Royal Free Hospital, London, UK, between 1994 and 2000.

Design

Retrospective case note review.

Methods

Data were extracted from the Royal Free HIV database identifying new diagnoses for 1994, 1997 and 2000. All case notes were reviewed and patients were included if they had their first positive HIV test at the Royal Free Hospital, or if they first tested positive elsewhere and attended the Royal Free HIV unit for their initial HIV care. Data extracted included sex, ethnicity, age, risk factor(s) for HIV, reason for test, clinical stage of disease, CD4 count and HIV RNA viral load at diagnosis.

Results

One hundred and forty‐four patients were identified for 1994, 136 for 1997 and 110 for 2000. Over this time period the proportion of white patients dropped from 72% (n = 104) to 48% (n = 53), P= 0.0001, whilst the proportion of black Africans rose from 24% (n = 34) to 45% (n = 49), P= 0.0004. The median CD4 count at diagnosis of the white cohort was 475 cells/µL in 1994 and 286/µL in 2000, P= 0.005, whilst in the black African patients it was 240/µL and 230/µL for the same years.

Conclusions

There has been a reduction in new HIV diagnoses among the white population and a rise in the black Africans at this centre between 1994 and 2000. The clinical and immunological parameters of HIV disease have worsened over this time period for the white group, but have remained stable in the black Africans.

     

Development of packaging cell lines for generation of adeno-associated virus vectors by lentiviral gene transfer of trans-complementary components

Adeno-associated virus (AAV) vector system has several useful advantages with regard to in vitro and in vivo gene transfer. However, their usages have been limited by cumbersome and labor-intensive vector production in the traditional method. To overcome limitations in AAV production, in this report, we explored the possibility of generating AAV packaging cell line, 293T R/C.VA.E2A.E4. cells, by using lentivirus-mediated transduction of Rep/Cap gene of AAV-2, VA RNA, E2A, and E4 genes of Ad5 into 293T cells. In packaging cell lines, it is important that supply of the AAV vector can be stably performed for long time. We showed that the 293T R/C.VA.E2A.E4. cells have stably maintained the transduced components after more than 10 passages and yielded high-titer AAV vectors, and the titer of AAV vectors did not decline even if culture of the packaging cells was continued for long time. The Rep/Cap and E4 gene products caused no remarkable cytotoxicity. The 293T R/C.VA.E2A.E4. cells might be able to tolerate the Rep/Cap and E4 gene products, or have less copy numbers of the Rep/Cap and E4 genes than the traditional method. Moreover, we showed that the AAV vectors derived from 293T R/C.VA.E2A.E4. cells infected the primary human CD34+ haematopoietic progenitor cells with high efficiency (50-70%). In the 293T R/C.VA.E2A.E4. cells, the AAV vectors can be generated by the transfection of one AAV vector plasmid, and large-scale AAV production can be easily achieved. It is important that cumbersome, variable, and costly transfection is avoided.