Severe skin reactions associated with cladribine in people with multiple sclerosis
MULTIPLE SCLEROSIS AND RELATED DISORDERS
Authors: Mateo-Casas, M.; Reyes, S.; O'Toole, E. A.; De Trane, S.; Yildiz, O.; Allen-Philbey, K.; Mathews, J.; Baker, D.; Giovannoni, G.; Schmierer, K.
Abstract
Objective: To report three cases of severe skin reactions in patients treated with cladribine for multiple sclerosis. Methods: Case study. Results: Patients developed severe rash 3-192 days after receiving cladribine. All were effectively treated with steroids and antihistamines. Additional doses of cladribine were administered after pretreatment with steroids and anti-histamines. One patient developed mild recurrence following re-exposure, which resolved within three days, whilst another patient tolerated re-exposure without further adverse reaction. Conclusion: Severe skin reactions, well described in patients receiving cladribine for treatment of haematological conditions, may occur in patients treated with this compound for multiple sclerosis. Neurologists need to be aware of this rare, but significant adverse reaction. Re-exposure may be safe with standard pre-treatment against allergic reactions.
Integrated analysis of sialotranscriptome and sialoproteome of the brown dog tick Rhipicephalus sanguineus (s.l.) : Insights into gene expression during blood feeding
JOURNAL OF PROTEOMICS
Authors: Tirloni, Lucas; Lu, Stephen; Calvo, Eric; Sabadin, Gabriela; Di Maggio, Lucia Sanchez; Suzuki, Motoshi; Nardone, Glenn; Vaz Jr, Itabajara da Silva; Ribeiro, Jose M. C.
Abstract
Tick salivary glands secrete a complex saliva into their hosts which modulates vertebrate hemostasis, immunity and tissue repair mechanisms. Transcriptomic studies revealed a large number of transcripts coding for structural and secreted protein products in a single tick species. These transcripts are organized in several large families according to their products. Not all transcripts are expressed at the same time, transcription profile switches at intervals, characterizing the phenomenon of "sialome switching". In this work, using transcriptomic and proteomic analysis we explored the sialome of Rhipicephalus sanguineus (s.l.) adult female ticks feeding on a rabbit. The correlations between transcriptional and translational results in the different groups were evaluated, confirming the "sialome switching" and validating the idea that the expression switch may serve as a mechanism of escape from the host immunity. Recombination breakpoints were identified in lipocalin and metalloprotease families, indicating this mechanism could be a possible source of diversity in the tick sialome. Another remarkable observation was the identification of host-derived proteins as a component of tick salivary gland content. These results and disclosed sequences contribute to our understanding of tick feeding biology, to the development of novel anti-tick methods, and to the discovery of novel pharmacologically active products. Significance: Ticks are a burden by themselves to humans and animals, and vectors of viral, bacterial, protozoal and helminthic diseases. Their saliva has anti-clotting, anti-platelet, vasodilatory and immunomodulatory activities that allows successful feeding and pathogen transmission. Previous transcriptomic studies indicate ticks to have over one thousand transcripts coding for secreted salivary proteins. These transcripts code for proteins of diverse families, but not all are transcribed simultaneously, but rather transiently, in a succession. Here we explored the salivary transcriptome and proteome of the brown dog tick, Rhipicephalus sanguineus. A protein database of over 20 thousand sequences was "de novo" assembled from over 600 million nucleotide reads, from where over two thousand polypeptides were identified by mass spectrometry. The proteomic data was shown to vary in time with the transcription profiles, validating the idea that the expression switch may serve as a mechanism of escape from the host immunity. Analysis of the transcripts coding for lipocalin and metalloproteases indicate their genes to contain signals of breakpoint recombination suggesting a new mechanism responsible for the large diversity in tick salivary proteins. These results and the disclosed sequences contribute to our understanding of the success ticks enjoy as ectoparasites, to the development of novel anti-tick methods, and to the discovery of novel pharma-cologically active products.