Mouse IL-15(Interleukin 15) ELISA Kit

BackgroundMutations in the Janus Kinase 3 (JAK3) gene cause an autosomal recessive form of severe combined immunodeficiency (SCID) usually characterized by the absence of both T and NK cells, but preserved numbers of B lymphocytes (T-B+NK-SCID). The detection of larger (>100bp) genomic duplications or deletions can be more difficult to be detected by PCR-based methods or standard NGS protocols, and a broad range of mutation detection techniques are necessary. MethodsWe report four unrelated Italian patients (two females and two males) with SCID phenotype. Protein expression, functional studies, molecular analysis by standard methods and NGS, and transcripts studies were performed to obtain a definitive diagnosis. ResultsHere, we describe four JAK3-deficient patients from four unrelated families. The first patient is homozygous for the known c.1951 C>T mutation causing the amino acidic change p.R651W. The other two patients, originating from the same small Italian town, resulted compound heterozygotes for the same g.15410_16542del deletion and two different novel mutations, g.13319_13321delTTC and c.933T>G (p.F292V), respectively. The fourth patient was compound heterozygous for the novel mutations p.V599G and p.W709R. Defective STAT5 phosphorylation after IL2 or IL15 stimulation corroborated the mutation pathogenicity. Concerning g.15410_16542del mutation, probably due to an unequal homologous recombination between Alu elements of JAK3 gene, microsatellites analysis revealed that both unrelated Pt2 and Pt3 and their carrier family members shared the same haplotype. These data support the hypothesis of a founder effect for the g.15410_16542del mutation that might have inherited in both unrelated families from the same ancient progenitor. ConclusionDifferent molecular techniques are still required to obtain a definitive diagnosis of AR-SCID particularly in all cases in which a monoallelic mutation is found by standard mutation scanning methods.

The interleukin-15 (IL-15) system is important for regulating both innate and adaptive immune responses, however, its role in autoimmune disease remained unclear. Here we found that Il15(-/-) and Il15ra(-1-) mice spontaneously developed late-onset autoimmune phenotypes. CD4+ T cells of the knockout mice showed elevated autoreactivity as demonstrated by the induction of lymphocyte infiltration in the lacrimal and salivary glands when transferred into nude mice. The antigen-presenting cells in the thymic medullary regions expressed IL-15 and IL-15R alpha, whose deficiency resulted in insufficient negative selection and elevated number of natural IL-17A-producing CD4+ thymocytes. These findings reveal previously unknown functions of the IL-15 system in thymocyte development, and thus a new layer of regulation in T cell-mediated autoimmunity. (C) 2014 Elsevier Ltd. All rights reserved.