Lymphoid Neogenesis in Murine Cardiac Allografts Undergoing Chronic Rejection

Lymphoid neogenesis is the process by which ectopic lymphoid accumulations that resemble lymph nodes arise in nonlymphoid tissues. Such lymphoid accumulations, known as tertiary lymphoid organs (TLO), are observed in chronic autoimmunity and they propagate immune pathology by setting up local antigen presenting sites. Whether lymphoid neogenesis occurs in transplanted organs and contributes to rejection is not well understood. To begin to address this question, we retrospectively analyzed 319 murine cardiac allografts for microscopic evidence of lymph-node-like structures. We found 78 allografts that had either classical TLO, characterized by discrete T- and B-cell zones and high endothelial venules (HEV) expressing peripheral node addressin (PNAd) (n = 34), or PNAd(+) HEV without organized lymphoid accumulations (n = 44). These changes were present in both short- and long-lived allografts and were invariably associated with rejection. Importantly, they occurred in 78% of allografts undergoing chronic rejection (n = 85) but in only 7% of allografts undergoing primarily acute rejection (n = 184). These findings indicate that, like autoimmunity, alloimmunity is associated with lymphoid neogenesis in the target organ and suggest a role for local T-cell activation in chronic allograft rejection.     

Discussing options between patients and health care professionals in genetic diagnosis: ethical and legal criteria

The specific characteristics of genetic data lead to ethical-legal conflicts in the framework of genetic diagnosis. Several international organisations, including UNESCO and the Council of Europe, have enacted rules referring to the use of genetic information. This paper discusses possible legal and ethical criteria that could be used in genetic testing.     

红细胞调控白细胞免疫功能新的自然实验研究体系

目的用血液免疫反应路线图实验体系评估红细胞在白细胞免疫活性中的作用。方法将0·3ml血浆加入0·2ml全血细胞悬液(全血细胞组)或0·2ml白细胞悬液(白细胞组)中,37℃温育1h,用免疫酶联法测定IL-8和IL-12水平,流式细胞仪测定白细胞膜CD4、CD8、CD35和CXCR4表达量。结果全血细胞组IL-8和IL-12水平(分别为5·96±4·26、9·84±2·23ρB·pg-1·ml-1)明显低于白细胞组(分别为15·09±9·86、13·59±3·69ρB·pg-1·ml-1,P<0·05),淋巴细胞CD4、CD35、CXCR4表达量(分别为37·79±12·00、154·66±70·00、34·40±20·45)明显高于白细胞组(分别为18·54±11·32、83·26±35·99、16·69±11·09,P<0.01),粒细胞CD35表达量(603·63±257·64)明显高于白细胞组(384·86±174·16,P<0.01)。成人全血细胞组淋巴细胞和粒细胞CD35和CXCR4表达量明显高于脐血全血细胞组(P<0·05或P<0·01)。结论红细胞是白细胞(包括T淋巴细胞、B淋巴细胞、NK细胞、树突状细胞、粒细胞等)免疫功能的调控者和指导者,脐血红细胞免疫调节功能明显下降;本研究为红细胞免疫调控活性测定提供了新的近似自然的方法。     

A Spanish version of the Family Assessment Device

Introduction  

This paper presents the results of a study on the psychometric properties of an authorized Spanish version of the McMaster Family Assessment Device, a self-report measure of family functioning.     

Discordance in HIV-1 viral loads and antiretroviral drug concentrations comparing semen and blood plasma

Objectives

For individuals not on antiretroviral therapy, the risk of heterosexual transmission of HIV appears negligible when blood plasma (BP) viral loads are <1500 HIV‐1 RNA copies/mL. It is not clear whether this observation can be extrapolated to individuals on highly active antiretroviral therapy (HAART). Because of differential tissue penetration, antiretroviral drug concentrations may be sufficient to maintain an undetectable viral load in the BP yet not achieve adequate levels to suppress HIV in the genital tract. Therefore, we wanted to correlate HIV viral loads and drug concentrations in semen plasma (SP) and BP.

Methods

Thirty‐three men were included. All were on combination antiretroviral therapy with an undetectable BP viral load for at least 1 year. Blood and semen samples were collected within 2 h of each other and tested for HIV RNA by the NucliSens QT (bioMerieux, St Laurent, QC, Canada) method; drug concentrations were determined by liquid chromatography tandem mass spectrometry.

Results

Two of the 33 patients (6.1%) with BP viral loads below detection had time‐matched HIV viral loads in SP ≥700 copies/mL. Both patients were on efavirenz, the SP concentrations of which were ≤10% of the levels in BP and well below the minimal therapeutic drug monitoring target concentration required to suppress HIV.

Conclusions

Because, at least in part, of poor drug penetration into the genital tract, an undetectable HIV viral load in the BP does not guarantee an undetectable viral load in semen. In view of this, caution should be taken in concluding that patients on HAART with suppressed viraemia are sexually non‐infectious.