Subject(s)
Base Sequence , Cathepsin C/genetics , Chromosomes, Human, Pair 11/genetics , Papillon-Lefevre Disease/genetics , Sequence Deletion , Adult , DNA Mutational Analysis , Female , Homozygote , Humans , Iran , Male , Pedigree , Young AdultABSTRACT
OBJECTIVES: To determine the potential of eotaxin-3 as a diagnostic marker for active disease and genetic susceptibility factor for Churg-Strauss syndrome (CSS). METHODS: A total of 37 patients with active, relapsed or inactive CSS, 123 healthy controls and 138 disease controls were studied. Clinical data were collected and serum levels of eotaxin-3 were determined. Ex vivo stability of eotaxin-3 in serum samples was tested. Furthermore, the association of single nucleotide polymorphisms (SNPs) in the eotaxin-3 gene with CSS was determined in 161 CSS patients and 124 healthy controls. RESULTS: Serum eotaxin-3 was highly elevated in active CSS patients. Neither eosinophilic diseases nor other small-vessel vasculitides were associated with high serum eotaxin-3 levels. Receiver operating characteristic curve analysis determined a sensitivity and specificity of 87.5 and 98.6% at a cut-off level of 80 pg/ml. None of the tested SNPs within the eotaxin-3 gene influenced the susceptibility to develop CSS. CONCLUSIONS: Serum eotaxin-3 is a sensitive and specific marker for the diagnosis of active CSS suitable for routine clinical practice. Previously described SNPs in the eotaxin-3 gene do not predict the risk of developing CSS.
Subject(s)
Chemokines, CC/genetics , Churg-Strauss Syndrome/diagnosis , Churg-Strauss Syndrome/genetics , Polymorphism, Single Nucleotide , Antibodies, Antineutrophil Cytoplasmic/blood , Biomarkers/blood , Chemokine CCL26 , Chemokines, CC/blood , Churg-Strauss Syndrome/blood , Colitis, Ulcerative/blood , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/genetics , Connective Tissue Diseases/blood , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/genetics , Diagnosis, Differential , Humans , Hypereosinophilic Syndrome/blood , Hypereosinophilic Syndrome/diagnosis , Hypereosinophilic Syndrome/genetics , Immunogenetic Phenomena , Parasitic Diseases/blood , Parasitic Diseases/diagnosis , Parasitic Diseases/genetics , Predictive Value of Tests , ROC CurveABSTRACT
Churg-Strauss syndrome (CSS) is a rare systemic necrotizing vasculitis associated with granuloma formation and severe blood and tissue eosinophilia. CSS occurs almost exclusively in patients with asthma. Its pathogenesis remains largely unknown, as triggering factors for CSS development have not been identified so far. AAb, such as anti-neutrophil cytoplasmic autoantibodies, are found in less than half of patients and possibly constitute a subtype of CSS with different clinical behaviour. On a cellular level, CSS is characterized by a strong Th2-type immune response. Th2-associated cytokines such as IL-4, IL-13 and IL-5 may precipitate the severe eosinophilia in CSS, while migration of Eos to inflammatory sites is possibly mediated by eotaxin-3. This review summarizes recent advances in the knowledge on epidemiology, clinical features, and pathogenesis of CSS.
