ABSTRACT
Hereditary angioedema (HAE) is a rare autosomic-dominant disorder characterized by a deficiency of C1 esterase inhibitor which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways that are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis during attack and remission state and n = 19 healthy subjects. The samples were tested for a panel of IL (Interleukin)-17-type cytokines (IL-1ß, IL-6, IL-10, granulocyte-macrophage colony stimulating factor (GM-CSF), IL-17, IL-21, IL-22, IL-23) and transforming growth factor-beta (TGF-ß) subtypes. Data indicate that there are variations of cytokine levels in HAE subjects comparing the condition during the crisis respect to the value in the remission phase, in particular type 17 signature cytokines are increased, whereas IL-23 is unmodified and TGF-ß3 is significantly reduced. When comparing healthy and HAE subjects in the remission state, we found a significant difference for IL-17, GM-CSF, IL-21, TGF-ß1 and TGF-ß2 cytokines. These results confirm and extend our previous findings indicating that in HAE there is operating an inflammatory activation process, which involves also T helper 17 (Th17) cytokines and TGF-ß isoforms, associated with localized angioedema attacks and characterized by elevated bradykinin levels.
Subject(s)
Angioedemas, Hereditary/diagnosis , Angioedemas, Hereditary/immunology , Gene Expression Regulation/immunology , Interleukin-17/immunology , Th17 Cells/immunology , Transforming Growth Factor beta/immunology , Adolescent , Adult , Aged , Angioedemas, Hereditary/genetics , Angioedemas, Hereditary/pathology , Bradykinin/genetics , Bradykinin/immunology , Bronchi/immunology , Bronchi/pathology , Case-Control Studies , Child , Complement C1 Inhibitor Protein/genetics , Complement C1 Inhibitor Protein/immunology , Female , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Humans , Interleukin-17/genetics , Interleukin-23/genetics , Interleukin-23/immunology , Interleukins/genetics , Interleukins/immunology , Intestines/immunology , Intestines/pathology , Male , Middle Aged , Subcutaneous Tissue/immunology , Subcutaneous Tissue/pathology , Th17 Cells/pathology , Transforming Growth Factor beta/genetics , Interleukin-22Subject(s)
Angioedemas, Hereditary/metabolism , Cytokines/metabolism , Interleukin-17/metabolism , Adolescent , Adult , Aged , Angioedemas, Hereditary/pathology , Child , Complement C1 Inhibitor Protein/analysis , Complement C1 Inhibitor Protein/genetics , Female , Humans , Male , Middle Aged , Mutation , Up-Regulation , Young AdultABSTRACT
BACKGROUND: Common polymorphisms of genes controlling inflammation-modulating cytokines and acute-phase proteins which play important roles in the pathogenesis of Alzheimer's disease (AD) have been shown to be associated with AD. AIMS: The immunological and immunogenetic markers potentially useful for the AD risk evaluation and diagnosis are briefly reviewed. CONCLUSION: The state-of-the-art of immunological and immunogenetic markers of AD indicates that new tools and strategies are necessary to identify gene products useful as diagnostic tools.
Subject(s)
Alzheimer Disease/genetics , Alzheimer Disease/immunology , Biomarkers/analysis , Acute-Phase Proteins/genetics , Acute-Phase Proteins/immunology , Alzheimer Disease/diagnosis , Apolipoproteins E/genetics , Apolipoproteins E/immunology , Cytokines/genetics , Cytokines/immunology , DNA/analysis , Gene Expression Regulation/genetics , Gene Expression Regulation/immunology , Humans , Inflammation/blood , Inflammation/genetics , Inflammation/immunology , Microglia/pathology , Oligonucleotide Array Sequence Analysis , Polymorphism, Genetic , Positron-Emission TomographyABSTRACT
The potential involvement of apoptosis in the pathogenesis of visceral leishmaniasis (VL) was examined by studying spontaneous and Leishmania antigen (LAg)-induced apoptosis using cryopreserved peripheral blood mononuclear cells (PBMC) of Sicilian patients with VL. Results indicate that monocytes and T lymphocytes from acute VL patients show a significantly higher level of apoptosis compared with that observed in healed subjects. The percentage of apoptotic cells was higher in monocytes than in T lymphocytes. T cells involved in programmed cell death (PCD) were mainly of the CD4(+) phenotype. In particular, the T helper 1-type (Th1) subset, as evaluated by chemokine receptor-5 (CCR5) expression, is involved in this process. Cell death in Th1-type uses a CD95-mediated mechanism. Furthermore, Th1-type CCR5(+) cells are prone to cell suicide in an autocrine or paracrine way, as attested by enhanced expression of CD95L in acute VL patients. The reduction in Th1-type cells by apoptosis was confirmed by the decrease in interferon-gamma secretion. In conclusion, apoptosis of monocytes, CD4(+) and CD4(+) CCR5(+) T cells could be involved in the failure of cell mediated immunity that is responsible for severe immune-depression in VL.
