Pattern recognition receptor expression is not impaired in patients with chronic mucocutanous candidiasis with or without autoimmune polyendocrinopathy candidiasis ectodermal dystrophy.
ABSTRACT Patients with chronic mucocutaneous candidiasis (CMC) have an unknown primary immune defect and are unable to clear infections with the yeast Candida. CMC includes patients with AIRE gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations. CMC patients have dysregulated cytokine production, suggesting that defective expression of pattern recognition receptors (PRRs) may underlie disease pathogenesis. In 29 patients with CMC (13 with APECED) and controls, we assessed dendritic cell (DC) subsets and monocyte Toll-like receptor (TLR) expression in blood. We generated and stimulated monocyte-derived (mo)DCs with Candida albicans, TLR-2/6 ligand and lipopolysaccharide and assessed PRR mRNA expression by polymerase chain reaction [TLR-1-10, Dectin-1 and -2, spleen tyrosine kinase (Syk) and caspase recruitment domain (CARD) 9] in immature and mature moDCs. We demonstrate for the first time that CMC patients, with or without APECED, have normal blood levels of plasmocytoid and myeloid DCs and monocyte TLR-2/TLR-6 expression. We showed that in immature moDCs, expression levels of all PRRs involved in anti-Candida responses (TLR-1, -2, -4, -6, Dectin-1, Syk, CARD9) were comparable to controls, implying that defects in PRR expression are not responsible for the increased susceptibility to Candida infections seen in CMC patients. However, as opposed to healthy controls, both groups of CMC patients failed to down-regulate PRR mRNA expression in response to Candida, consistent with defective DC maturation, as we reported recently. Thus, impaired DC maturation and consequent altered regulation of PRR signalling pathways rather than defects in PRR expression may be responsible for inadequate Candida handling in CMC patients.
Article: [Advantages and limitations of whole-body bone marrow MRI using Turbo-STIR sequences in comparison to planar bone scans] .[show abstract] [hide abstract]
ABSTRACT: At modern MRI tomographs the whole body can be screened for bone marrow metastases within 45 min. AIM of this study was to evaluate the diagnostic advantages and disadvantages of a whole-body bone marrow MRI protocol using Turbo Short Tau Inversion Recovery [STIR] sequences in comparison to planar bone scintigraphy (SZ). In order to screen for bone metastases within two weeks SZ and whole-body MRI with Turbo-STIR-sequences were performed in 20 patients with known breast cancer. For further evaluation five regions were defined: skull, spine including the pelvis, femora, humeri and ribs including scapulae and sternum. In 9/20 patients neither with SZ nor with MRI bone metastases were detected (staging M0). Among the remaining 11 patients SZ detected 109 and MRI 150 lesions which were typical for bone metastases. All of these 11 patients were staged M1 correspondingly with both methods. Within the thorax (ribs, sternum, scapulae) MRI discovered only 6/17 and within the skull 0/6 lesions which were suspicious for metastases in SZ. Inversely MRI identified much more metastatic lesions than SZ within the femora (20/16), the humeri (14/12) and the spine including the pelvis (110/58). Susceptibility-, truncation-, chemical-shift-, third arm- and particularly pulsation artifacts along with the impossibility to chose slice orientation equally advantageous for all regions of the body cause impaired image quality of MRI whole body scanning. Therefore, concerning the detection rate of bone metastases within the thorax (ribs, sternum and scapulae) and the skull, conventional Turbo-STIR-MRI whole-body scans are even less accurate than conventional planar bone scintigraphy in those regions.Nuklearmedizin 10/2000; 39(6):174-9. · 1.28 Impact Factor