NOD2, CD14 and TLR4 mutations do not influence response to adalimumab in patients with Crohn’s disease: a preliminary report

Introduction: adalimumab is a recombinant fully-human monoclonal immunoglobulin (IgG1) antibody utilized in the treatment of Crohn´s disease. Unfortunately no clinical or genetic markers exist to predict response to anti-tumor necrosis factor-alpha (TNF) therapy. The aim of this study was to evaluate the association between selected genes involved in cytokine regulation and response to adalimumab treatment in Crohn’s disease. Methods: twenty-four patients with Crohn’s disease either naïve (n = 8) or had lost response or were unable to tolerate the chimeric anti-TNF antibody infliximab (n=16) were enrolled in the study. Patients were genotyped for main polymorphisms in NOD2, CD14 and TLR4 genes. Response to adalimumab treatment was defined as a decrease of Crohn’s disease activity index of at least 100 points or a closure of at least 50% of fistulas in case of fistulizing Crohn’s disease. Results: overall, 75% of patients did respond to treatment. However, no statistically significant association was found between any of the genotypes and the response to adalimumab. Conclusions: in our small study group no association between the studied polymorphisms and response to adalimumab was apparent. Systematic studies to search for genetic markers of response to anti-TNF therapy are necessary(AU)

Pattern recognition at the maternal-fetal interface.

Intrauterine infections represent a significant threat to fetal well-being and pregnancy outcome. Recent studies suggest that non-immune cells of the maternal-fetal interface can actively recognize and respond to microbes through pattern recognition receptors, in order to control pathogens that may compromise the pregnancy. However, these same innate immune responses may inadvertently lead to excessive inflammation or apoptosis at the maternal-fetal interface. Thus, pattern recognition receptors may play a key role in infection-related pregnancy complications. This review discusses what is currently known about the role of Toll-like receptors and NOD-like receptors in controlling infections at the maternal-fetal interface, and what impact their function may have on pregnancy.