| 1. |
- Foell, Dirk, et al.
(författare)
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A novel serum calprotectin (MRP8/14) particle-enhanced immuno-turbidimetric assay (sCAL turbo) helps to differentiate systemic juvenile idiopathic arthritis from other diseases in routine clinical laboratory settings
- 2023
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Ingår i: Molecular and Cellular Pediatrics. - : Springer. - 2194-7791. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Differential diagnosis in children with signs of unprovoked inflammation can be challenging. In particular, differentiating systemic juvenile idiopathic arthritis (SJIA) from other diagnoses is difficult. We have recently validated the complex of myeloid-related proteins 8/14 (MRP8/14, also known as S100A8/A9 complex or serum calprotectin) as a helpful biomarker supporting the diagnosis of SJIA. The results were subsequently confirmed with a commercial ELISA. However, further optimization of the analytical technology is important to ensure its feasibility for large-scale use in routine laboratory settings.Methods: To evaluate the accuracy in identifying children with SJIA, the performance of a particle-enhanced immuno-turbidimetric assay for serum calprotectin (sCAL turbo) on an automated laboratory instrument was analyzed. Samples from 615 children were available with the diagnoses SJIA (n = 99), non-systemic JIA (n = 169), infections (n = 51), other inflammatory diseases (n = 126), and acute lymphoblastic leukemia (ALL, n = 147). In addition, samples from 23 healthy controls were included.Results: The sCAL turbo assay correlated well with the MRP8/14 ELISA used in previous validation studies (r = 0.99, p < 0.001). It could reliably differentiate SJIA from all other diagnoses with significant accuracy (cutoff at 10,500 ng/ml, sensitivity 84%, specificity 94%, ROC area under curve 0.960, p < 0.001).Conclusions: Serum calprotectin analyses are a helpful tool supporting the diagnosis of SJIA in children with prolonged fever or inflammatory disease. Here, we show that an immuno-turbidimetric assay for detection of serum calprotectin on an automated laboratory instrument can be implemented in clinical laboratory settings to facilitate its use as a diagnostic routine test in clinical practice.
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| 2. |
- Bohm, Marek, et al.
(författare)
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Clinical features of childhood granulomatosis with polyangiitis (wegener's granulomatosis)
- 2014
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Ingår i: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 12:18
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis (WG), belongs to the group of ANCA-associated necrotizing vasculitides. This study describes the clinical picture of the disease in a large cohort of GPA paediatric patients.Children with age at diagnosis ≤ 18 years, fulfilling the EULAR/PRINTO/PRES GPA/WG classification criteria were extracted from the PRINTO vasculitis database. The clinical signs/symptoms and laboratory features were analysed before or at the time of diagnosis and at least 3 months thereafter and compared with other paediatric and adult case series (>50 patients) derived from the literature. Findings The 56 children with GPA/WG were predominantly females (68%) and Caucasians (82%) with a median age at disease onset of 11.7 years, and a median delay in diagnosis of 4.2 months. The most frequent organ systems involved before/at the time of diagnosis were ears, nose, throat (91%), constitutional (malaise, fever, weight loss) (89%), respiratory (79%), mucosa and skin (64%), musculoskeletal (59%), and eye (35%), 67% were ANCA-PR3 positive, while haematuria/proteinuria was present in > 50% of the children. In adult series, the frequency of female involvement ranged from 29% to 50% with lower frequencies of constitutional (fever, weight loss), ears, nose, throat (oral/nasal ulceration, otitis/aural discharge), respiratory (tracheal/endobronchial stenosis/obstruction), laboratory involvement and higher frequency of conductive hearing loss than in this paediatric series. Conclusions Paediatric patients compared to adults with GPA/WG have similar pattern of clinical manifestations but different frequencies of organ involvement.
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| 3. |
- Brix, Ninna, et al.
(författare)
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Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests
- 2023
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Ingår i: The Journal of Pediatrics. - : Elsevier. - 0022-3476 .- 1097-6833. ; 258
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the predictive value of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of inflammatory cytokines in order to differentiate the child with acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA).Study design: In this cross-sectional study, we measured S100A9, S100A12, and 14 cytokines in serum from children with ALL (n = 150, including 27 with arthropathy) and JIA (n = 236). We constructed predictive models computing areas under the curve (AUC) as well as predicted probabilities in order to differentiate ALL from JIA. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated 10-fold cross-validation and recalibration, adjusted for age.Results: In ALL, the levels of S100A9, S100A12, interleukin (IL)-1 beta, IL-4, IL-13, IL-17, matrix metalloproteinase-3, and myeloperoxidase were low compared with JIA (P < .001). IL-13 had an AUC of 100% (95% CI 100%-100%) due to no overlap between the serum levels in the 2 groups. Further, IL-4 and S100A9 had high predictive performance with AUCs of 99% (95% CI 97%-100%) and 98% (95% CI 94%-99%), respectively, exceeding both hemoglobin, platelets, C-reactive protein, and erythrocyte sedimentation rate.Conclusions: The biomarkers S100A9, IL-4, and IL-13 might be valuable markers to differentiate ALL from JIA.
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| 4. |
- Brix, Ninna, et al.
(författare)
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Inflammatory Biomarkers Can Differentiate ALL with Arthropathy from JIA Better Than Standard Blood Tests.
- 2023
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Ingår i: The Journal of pediatrics. - 1097-6833. ; 258
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the predictive value of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of inflammatory cytokines in order to differentiate the child with acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA).In this cross-sectional study, we measured S100A9, S100A12, and 14 cytokines in serum from children with ALL (n=150, including 27 with arthropathy) and JIA (n=236). We constructed predictive models computing areas under the curve (AUC) as well as predicted probabilities in order to differentiate ALL from JIA. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated 10-fold cross-validation and recalibration, adjusted for age.In ALL, the levels of S100A9, S100A12, IL-1 beta, IL-4, IL-13, IL-17, MMP-3, and MPO were low compared with JIA (p <0.001). IL-13 had an AUC of 100% (95% CI 100-100%) due to no overlap between the serum levels in the two groups. Further, IL-4 and S100A9 had high predictive performance with AUCs of 99% (95% CI 97-100%) and 98% (95% CI 94-99%), respectively, exceeding both hemoglobin, platelets, C-reactive protein, and erythrocyte sedimentation rate.The biomarkers S100A9, IL-4, and IL-13 might be valuable markers to differentiate ALL from JIA.
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| 5. |
- Sundqvist, Martina, et al.
(författare)
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Increased intracellular oxygen radical production in neutrophils during febrile episodes of PFAPA syndrome.
- 2013
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Ingår i: Arthritis and rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 65:11, s. 2971-2983
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome is an autoinflammatory disease of unknown etiology that primarily affects preschool children. PFAPA is characterized by recurrent attacks of fever and inflammatory symptoms consistent with the disease acronym. Since autoinflammatory diseases by definition are mediated by cells of the innate immune system, we aimed at evaluating functional features of neutrophils, the most abundant innate immune cell in circulation, in PFAPA syndrome. Methods: Blood neutrophils, obtained from PFAPA patients during both febrile and asymptomatic afebrile phases of disease, as well as from healthy children (afebrile controls) and children with fever and abdominal pain (febrile controls) were analysed for three key neutrophil characteristics: (i) apoptosis (measured by Annexin V/7AAD staining), (ii) production of reactive oxygen species (ROS; by luminol/isoluminol-amplified chemiluminescence), and (iii) priming status (as responsiveness to galectin-3 and upregulation of CD11b). Results: Compared to neutrophils from both PFAPA patients in an afebrile interval and from febrile controls, neutrophils obtained during a PFAPA flare produced elevated levels of intracellular NADPH-oxidase-derived ROS, had significantly diminished rates of spontaneous apoptosis, and displayed signatures of priming. In contrast, neutrophils from afebrile PFAPA patients had a significantly elevated rate of spontaneous apoptosis compared to neutrophils from afebrile controls. Conclusions: We demonstrate that three key aspects of neutrophil innate immune function, namely apoptosis, priming, and generation of an intracellular oxidative burst are altered, most prominently during febrile attacks in PFAPA syndrome. © 2013 American College of Rheumatology.
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