ABSTRACT
Expression features of genetic landscape which predispose an individual to the type 1 diabetes are poorly understood. We addressed this question by comparing gene expression profile of freshly isolated peripheral blood mononuclear cells isolated from either patients with type 1 diabetes (T1D), or their first-degree relatives or healthy controls. Our aim was to establish whether a distinct type of 'prodiabetogenic' gene expression pattern in the group of relatives of patients with T1D could be identified. Whole-genome expression profile of nine patients with T1D, their ten first-degree relatives and ten healthy controls was analysed using the human high-density expression microarray chip. Functional aspects of candidate genes were assessed using the MetaCore software. The highest number of differentially expressed genes (547) was found between the autoantibody-negative healthy relatives and the healthy controls. Some of them represent genes critically involved in the regulation of innate immune responses such as TLR signalling and CCR3 signalling in eosinophiles, humoral immune reactions such as BCR pathway, costimulation and cytokine responses mediated by CD137, CD40 and CD28 signalling and IL-1 proinflammatory pathway. Our data demonstrate that expression profile of healthy relatives of patients with T1D is clearly distinct from the pattern found in the healthy controls. That especially concerns differential activation status of genes and signalling pathways involved in proinflammatory processes and those of innate immunity and humoral reactivity. Thus, we posit that the study of the healthy relative's gene expression pattern is instrumental for the identification of novel markers associated with the development of diabetes.
Subject(s)
Autoantibodies/genetics , Diabetes Mellitus, Type 1/genetics , Gene Expression Regulation/immunology , Leukocytes, Mononuclear/metabolism , Adolescent , Adult , Antigens, CD/genetics , Antigens, CD/immunology , Autoantibodies/biosynthesis , Autoimmunity , Case-Control Studies , Child , Child, Preschool , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/pathology , Family , Female , Gene Expression Profiling , Genome-Wide Association Study , Humans , Immunity, Humoral , Immunity, Innate , Infant , Interleukin-1/genetics , Interleukin-1/immunology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/pathology , Male , Molecular Sequence Annotation , Primary Cell Culture , Receptors, CCR3/genetics , Receptors, CCR3/immunology , Signal Transduction , Toll-Like Receptors/genetics , Toll-Like Receptors/immunologyABSTRACT
The aim of the study was to evaluate the possibility of detecting thyroid cancer recurrences without the need for withdrawal of thyroid suppressive treatment. Upper-body or whole-body scintigraphy was performed in a group of 200 patients evaluated for differentiated thyroid cancers in 1993 and 1994 using technetium-99m sestamibi. Scans were performed 20-30min following i.v. administration of 500MBq of 99mTc-methoxyisobutylisonitrile (MIBI). Bone and lung metastases were detected with very high sensitivity and specificity, with a very high predictive value of negative results and a somewhat lower predictive value of positive results. The sensitivity and specificity of findings in the neck were lower but the predictive value of negative results was high. Whole-body scans with 99mTc-MIBI are a useful tool in the follow-up of patients with differentiated thyroid cancer, for the detection of distant metastatic lesions.
