OS is invariably fatal within the first months of life unless immune restoration is performed by haematopoietic stem cell transplantation (HSCT). Abnormal autoreactive T cells may infiltrate and expand BI 6727 order into different organs (e.g. skin, gut, liver and spleen) and cause significant tissue damage [3]. Poor clinical status before the HSCT results in high transplantation-related mortality [4]. In the past, interferon (IFN) gamma was used to counteract the predominance of T cell activation and proliferation,

to down-regulate interleukin (IL)-4 and IL-5 production, to modulate the inflammatory reaction by enhancing phagocytic functions and to improve clinical status [5]. Today, topical/systemic steroids or cyclosporin A (CsA) are the widely used medications to control the skin manifestations [6]. CsA, a known calcineurin inhibitor, seems to act on the IL-2 by inhibiting its production and

repressing the activity of various transcription factors, thus leading to a decrease in the proliferation of the activated lymphocyte [7,8]. Moreover, it may interfere with specific signal transduction pathways which are important to the hypertrophic response [9]. Little is known about the immune modifications induced by CsA in OS patients. Such information will further improve our understanding the pathophysiology underlying OS and mechanisms of potential treatment modalities. Here we describe two OS patients selleck kinase inhibitor and their clinical and immune response to CsA. Two patients with recombinase activating gene (RAG)2 deficiency SCID and clinical and immunological features suggestive of the diagnosis of OS phenotype were reported. Significant transplacentally acquired maternal T lymphocyte was excluded in both patients by fluorescence in-situ hybridization (FISH). The study was approved by the Institutional Review Board and informed consent was obtained from all participants’ Calpain parents. Cell surface markers of peripheral blood mononuclear cells (PBMCs) and lymphocyte proliferative

responses to mitogens were performed as described previously. The amount of signal joint (sj) T cell receptor excision circles (Trecs) were determined by quantitative real-time reverse transcriptase – polymerase chain reaction (qRT–PCR). Reactions were performed using 0·25–0·5 µg genomic DNA extracted from the patients’ PBMCs. The standard curve was constructed by using serial dilutions of a known Trec plasmid (generously provided by Dr Daniel Douek, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA). The number of Trecs in a given sample was calculated automatically by comparing the obtained Ct value of a patient’s sample to the standard curve using an absolute quantification algorithm.