TY - JOUR A1 - Mazon, Melody A1 - Larouche, Valérie A1 - St-Louis, Maryse A1 - Schindler, Detlev A1 - Carreau, Madeleine T1 - Elevated blood levels of Dickkopf-1 are associated with acute infections JF - Immunity, Inflammation and Disease N2 - Introduction Dickkopf-1 (DKK1) is a soluble protein and antagonist of the Wnt/β-catenin signaling pathway. DKK1 is found elevated in serum from patients affected with various types of cancers and in some instances, it is considered a diagnostic and prognostic biomarker. Elevated serum levels of DKK1 have also been detected in animal models of chronic inflammatory diseases. Previous work from our laboratory has demonstrated upregulation of DKK1 in cells and mouse models of the bone marrow failure (BMF) and cancer-prone disease Fanconi anemia (FA). The present study aimed to investigate whether DKK1 blood levels in patients are associated with FA or inflammatory responses to acute infections. Methods Plasma samples were collected from 58 children admitted to the Centre Mère-Enfant Soleil du Centre Hospitalier de Québec-Université Laval with signs of acute infections. Blood plasma specimens were also collected from healthy blood donors at the Héma-Québec blood donor clinic. Plasmas from patients diagnosed with FA were also included in the study. DKK1 levels in blood plasmas were assessed by standard ELISA. Results Patients with acute infections showed dramatically high levels of DKK1 (6072 ± 518 pg/ml) in their blood compared to healthy blood donors (1726 ± 95 pg/ml). No correlations were found between DKK1 levels and C reactive protein (CRP) concentration, platelet numbers, or white blood cell counts. Patients with FA showed higher DKK1 plasma levels (3419 ± 147.5 pg/ml) than healthy blood donors (1726 ± 95 pg/ml) but significantly lower than patients with acute infections. Conclusion These findings suggest that blood DKK1 is elevated in response to infections and perhaps to inflammatory responses. KW - blood plasma KW - Dickkopf-1 KW - ELISA KW - Fanconi anemia KW - infections Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222171 VL - 6 ER - TY - JOUR A1 - Karastaneva, Anna A1 - Lanz, Sofia A1 - Wawer, Angela A1 - Behrends, Uta A1 - Schindler, Detlev A1 - Dietrich, Ralf A1 - Burdach, Stefan A1 - Urban, Christian A1 - Benesch, Martin A1 - Seidel, Markus G. T1 - Immune thrombocytopenia in two unrelated Fanconi anemia patients - a mere coincidence? JF - Frontiers in Pediatrics N2 - Thrombocytopenia and pancytopenia, occurring in patients with Fanconi anemia (FA), are interpreted either as progression to bone marrow failure or as developing myelodysplasia. On the other hand, immune thrombocytopenia (ITP) represents an acquired and often self-limiting benign hematologic disorder, associated with peripheral, immune-mediated, platelet destruction requiring different management modalities than those used in congenital bone marrow failure syndromes, including FA. Here, we describe the clinical course of two independent FA patients with atypical – namely immune – thrombocytopenia. While in one patient belonging to complementation group FA-A, the ITP started at 17 months of age and showed a chronically persisting course with severe purpura, responding well to intravenous immunoglobulins (IVIG) and later also danazol, a synthetic androgen, the other patient (of complementation group FA-D2) had a self-limiting course that resolved after one administration of IVIG. No cytogenetic aberrations or bone marrow abnormalities other than FA-typical mild dysplasia were detected. Our data show that acute and chronic ITP may occur in FA patients and impose individual diagnostic and therapeutic challenges in this rare congenital bone marrow failure/tumor predisposition syndrome. The management and a potential context of immune pathogenesis with the underlying marrow disorder are discussed. KW - immune thrombocytopenia KW - bone marrow failure syndrome KW - Evans syndrome KW - danazol KW - FANCA KW - FANCD2 KW - Fanconi anemia KW - DNA repair defect Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149837 VL - 3 IS - 50 ER -