Equine Anti-Thymocyte Globulin (ATGAM) administration in patient with previous rabbit Anti-Thymocyte Globulin (Thymoglobulin) induced serum sickness: A case report

Thymoglobulin is a rabbit-derived anti-thymocyte antibody directed at T-cells and commonly used for induction immunosuppression therapy in solid organ transplantation, especially in immunologically high risk kidney transplant recipients. Despite its frequent use and efficacy, the heterologous makeup of thymoglobulin can induce the immune system resulting in serum sickness which typically presents with rash, fever, fatigue, and poly-arthralgia in the weeks following drug exposure. ATGAM is another anti-thymocyte antibody, targeting the same epitopes, but differs from thymoglobulin by the animal in which the preparations are generated (equine vs. rabbit). Herein, we present a case of a patient with a known history of thymoglobulin-induced serum sickness, who presented with evidence of acute cellular and vascular rejection at their 12-month post-operative visit. Given their immunologically high risk status, they were successfully treated with ATGAM with improvement in their rejection and kidney function. To the author’s knowledge, this is the first case report of successful administration of ATGAM in a patient with a documented history of thymoglobulin induced serum sickness, demonstrating a possible treatment option for acute rejection in patients with reactions to thymoglobulin.&nbsp

Bioinformatic profiling of the transcriptional response of adult rat cardiomyocytes to distinct fatty acids*s⃞

Diabetes mellitus, obesity, and dyslipidemia increase risk for cardiovascular disease, and expose the heart to high plasma fatty acid (FA) levels. Recent studies suggestthat distinct FA species are cardiotoxic (e.g., palmitate), while others are cardioprotective (e.g., oleate), although the molecular mechanisms mediating these observations are unclear. The purpose of the present study was to investigate the differential effects of distinct FA species (varying carbon length and degree of saturation) on adult rat cardiomyocyte (ARC) gene expression.ARCs were initialy challenged with 0.4 mM octanoate (8:0), palmitate (16:0), stearate (18:0), oleate (18:1), or linoleate (18:2) for 24 h. Microarray analysis revealed differential regulation of gene expression by the distinct FAs; the order regarding the number of genes whose expression was influenced by a specific FA was octanoate (1,188) > stearate (740) > palmitate (590) > oleate (83) > linoleate (65). In general, cardioprotective FAs (e.g., oleate) increased expression of genes promoting FA oxidation to a greater extent than cardiotoxic FAs (e.g., palmitate), whereas the latter induced markers of endoplasmic reticulum and oxidative stress. Subsequent RT-PCR analysis revealed distinct time- and concentration-dependent effects of these FA species, in a gene-specific manner. For example, stearate- and palmitate-mediated ucp3 induction tended to be transient (i.e., initial high induction, followed by subsequent repression), whereas oleate-mediated induction was sustained. These findings may provide insight into why diets high in unsaturated FAs (e.g., oleate) are cardioprotective, whereas diets rich in saturated FAs (e.g., palmitate) are not

Humanized mice for immune system investigation: progress, promise and challenges.

Significant advances in our understanding of the in vivo functions of human cells and tissues and the human immune system have resulted from the development of \u27humanized\u27 mouse strains that are based on severely immunodeficient mice with mutations in the interleukin-2 receptor common γ-chain locus. These mouse strains support the engraftment of a functional human immune system and permit detailed analyses of human immune biology, development and functions. In this Review, we discuss recent advances in the development and utilization of humanized mice, the lessons learnt, the remaining challenges and the promise of using humanized mice for the in vivo study of human immunology