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1.
J Dtsch Dermatol Ges ; 21(5): 464-470, 2023 05.
Article in English | MEDLINE | ID: mdl-36920284

ABSTRACT

BACKGROUND AND OBJECTIVES: Antinuclear antibodies (ANA) detected by HEp2 cell immunofluorescence staining are a characteristic finding in patients with connective tissue disease (CTD). However, even detection of highly elevated ANA is not conclusive for CTD and can result in misdiagnosis. Anti-DFS70 antibodies are ANA, which may also be highly elevated in people without CTD. Thus, we wanted to evaluate whether they could cause misdiagnosis of CTD. Since anti-DSF70 antibodies have been associated with atopic dermatitis (AD) in Japan, we wanted to investigate this association and its potential diagnostic relevance in Germany. PATIENTS AND METHODS: We retrospectively analyzed data of 40 patients referred for first consultation on CTD and prospectively analyzed the prevalence of anti-DFS70 antibodies in 110 AD patients and 89 controls. RESULTS: We could not confirm CTD in 75% of our referred patients, 26% of whom had already received systemic treatments. DFS70-typical fluorescence staining was detected in 35% and definitive anti-DFS70 antibodies in 12.5% of these patients. DFS70-typical fluorescence staining was detected in 22% of AD patients and anti-DFS70 antibodies in 10% (versus 5.6% and 0% in control patients, P < 0.001). CONCLUSIONS: Anti-DFS70 antibodies are significantly associated with AD and could be responsible for misdiagnosis of CTD.


Subject(s)
Connective Tissue Diseases , Dermatitis, Atopic , Humans , Dermatitis, Atopic/diagnosis , Retrospective Studies , Adaptor Proteins, Signal Transducing , Transcription Factors , Connective Tissue Diseases/diagnosis , Antibodies, Antinuclear , Diagnostic Errors
2.
Rheumatology (Oxford) ; 61(7): 3082-3092, 2022 07 06.
Article in English | MEDLINE | ID: mdl-34559193

ABSTRACT

OBJECTIVES: Differential diagnosis in children with prolonged fever is challenging. In particular, differentiating systemic-onset JIA (SJIA) from infectious diseases is difficult. Biomarkers are needed that support the diagnostic work-up. The aim of this study was to validate the usefulness of Myeloid-related protein 8/14 (MRP8/14) measurements in the diagnostic work-up of febrile children and to transfer it to clinical practice. METHODS: Data for 1110 paediatric patients were included and divided into two cohorts: (cohort A) for validation of MRP8/14 test performance with three different testing systems: the experimental ELISA, commercial ELISA and an innovative (point-of-care test) lateral flow immunoassay (LFIA); (cohort B) to validate the diagnostic accuracy with the two latter assays. RESULTS: In cohort A (n = 940), MRP8/14 was elevated in SJIA (12 110 ± 2650 ng/ml mean ± 95% CI) compared with other diagnoses (including infections and autoinflammatory diseases; 2980 ± 510 ng/ml) irrespective of fever and anti-inflammatory treatment (P < 0.001). In untreated patients with fever (n = 195) MRP8/14 levels in SJIA (19 740 ± 5080 ng/ml) were even higher compared with other diagnoses (4590 ± 1160 ng/ml) (P < 0.001, sensitivity 73%, specificity 90%). In group B1, the performance of the tests was confirmed in untreated patients with fever (n = 170): commercial ELISA (sensitivity 79%, specificity 89%) and LFIA (sensitivity 84%, specificity 81%). Compared with ferritin, IL-18, ESR, soluble IL-2 receptor and procalcitonin, MRP8/14 showed the best accuracy. CONCLUSION: MRP8/14 serum analyses have been validated as a helpful tool supporting the diagnosis of SJIA in febrile children. The results could be confirmed with commercial ELISA and LFIA enabling a rapid diagnostic point-of-care screening test.


Subject(s)
Arthritis, Juvenile , Anti-Inflammatory Agents/therapeutic use , Arthritis, Juvenile/drug therapy , Biomarkers , Calgranulin A/metabolism , Child , Cohort Studies , Fever/drug therapy , Fever/etiology , Humans
3.
FEBS Lett ; 566(1-3): 241-6, 2004 May 21.
Article in English | MEDLINE | ID: mdl-15147902

ABSTRACT

Here, we identify ADP-ribosylation factor (ARF)-like 7 (ARL7) as the only ARF- and ARL-family member whose mRNA-expression is induced by liver X-receptor/retinoid X-receptor agonists or cholesterol loading in human macrophages. Moreover, subcellular distribution of mutant and wild type ARL7-enhanced green fluorescent protein (EGFP) supports that ARL7 may be involved in a vesicular transport step between a perinuclear compartment and the plasma membrane. Therefore, we investigated the effect of ARL7 over-expression on the cholesterol secretory pathway. We found that expression of wild type and dominant active ARL7-EGFP stimulated the rate of apolipoprotein AI-specific cholesterol efflux 1.7- and 2.8-fold. In contrast, expression of the dominant negative form of ARL7-EGFP led to approximately 50% inhibition of cholesterol efflux. This data is consistent with a model in which ARL7 is involved in transport between a perinuclear compartment and the plasma membrane apparently linked to the ABCA1-mediated cholesterol secretion pathway.


Subject(s)
ADP-Ribosylation Factors/biosynthesis , Apolipoprotein A-I/metabolism , Cholesterol/metabolism , ADP-Ribosylation Factors/genetics , ADP-Ribosylation Factors/metabolism , Biological Transport , Cholesterol/pharmacology , Gene Expression , Green Fluorescent Proteins , HeLa Cells , Humans , Luminescent Proteins/genetics , Macrophages/cytology , Macrophages/metabolism , Monocytes/cytology , RNA, Messenger/biosynthesis , Receptors, Cytoplasmic and Nuclear/agonists , Receptors, Retinoic Acid/agonists , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Subcellular Fractions/metabolism , Transfection
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