TY - JOUR A1 - Dirks, Johannes A1 - Fischer, Jonas A1 - Haase, Gabriele A1 - Holl-Wieden, Annette A1 - Hofmann, Christine A1 - Girschick, Hermann A1 - Morbach, Henner T1 - CD21\(^{lo/−}\)CD27\(^−\)IgM\(^−\) Double-Negative B Cells Accumulate in the Joints of Patients With Antinuclear Antibody-Positive Juvenile Idiopathic Arthritis JF - Frontiers in Pediatrics N2 - Juvenile idiopathic arthritis (JIA) encompasses a heterogeneous group of diseases. The appearance of antinuclear antibodies (ANAs) in almost half of the patients suggests B cell dysregulation as a distinct pathomechanism in these patients. Additionally, ANAs were considered potential biomarkers encompassing a clinically homogenous subgroup of JIA patients. However, in ANA+ JIA patients, the site of dysregulated B cell activation as well as the B cell subsets involved in this process is still unknown. Hence, in this cross-sectional study, we aimed in an explorative approach at characterizing potential divergences in B cell differentiation in ANA+ JIA patients by assessing the distribution of peripheral blood (PB) and synovial fluid (SF) B cell subpopulations using flow cytometry. The frequency of transitional as well as switched-memory B cells was higher in PB of JIA patients than in healthy controls. There were no differences in the distribution of B cell subsets between ANA- and ANA+ patients in PB. However, the composition of SF B cells was different between ANA- and ANA+ patients with increased frequencies of CD21\(^{lo/−}\)CD27\(^−\)IgM\(^−\) “double negative” (DN) B cells in the latter. DN B cells might be a characteristic subset expanding in the joints of ANA+ JIA patients and are potentially involved in the antinuclear immune response in these patients. The results of our explorative study might foster further research dissecting the pathogenesis of ANA+ JIA patients. KW - juvenile idiopathic arthritis KW - B cells KW - antinuclear antibodies KW - synovial fluid KW - double negative B cells Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236286 SN - 2296-2360 VL - 9 ER - TY - JOUR A1 - Klenke, Daniela A1 - Quast, Anja A1 - Prelog, Martina A1 - Holl-Wieden, Annette A1 - Riekert, Maximilian A1 - Stellzig-Eisenhauer, Angelika A1 - Meyer-Marcotty, Philipp T1 - TMJ pathomorphology in patients with JIA-radiographic parameters for early diagnosis- JF - Head & Face Medicine N2 - Background Juvenile idiopathic arthritis (JIA) is often accompanied by pathomorphological changes to the temporomandibular joint (TMJ). By analyzing orthodontical orthopantomograms of JIA patients the aims of the study were a) classification of condyle changes, b) quantification of bony asymmetries of condylar destruction and c) detection of relationships between disease duration and TMJ-involvement. Patients/Methods 46 caucasian JIA-patients (28 female; 18 male; < 16.0 years) were enrolled, each joint (n = 92) was morphologically assessed by means of orthopantomogram, quantitatively analysed and compared with duration of general disease. Condyle morphology was assessed using the Billiau scale for severity of destruction [1]. The quantitative analysis was based on ratios of condyle, ramus and mandible height. Results Patients were divided into groups (Group I – slightly affected, n = 36; Billiau severity 0–2; condyle findings: X-ray normal, condyle erosions, condylar flattening; Group II – severely affected, N = 10; Billiau severity 3–4; condyle findings: condylar flattenings and erosions, unilateral/bilateral complete loss of condyles), based on morphological analysis of condylar destruction. Duration of disease was significantly longer in Group II (8.9 ± 5.2 years) than in Group I (4.6 ± 4.7 years). Asymmetries of condyle, ramus and mandible height, quantitatively analysed by contralateral comparison, were significantly more marked in patients of Group II than of Group I. Conclusions Orthopantomogram imaging can be used in orthodontics clinical routine to detect TMJ-pathologies and is an important reference for monitoring progression of JIA. Classification into severe and slightly affected TMJ is possible by analysis of condylar pathomorphology. An association between degree of destruction, extent of lower jaw asymmetry and disease duration is suggested by the results. KW - juvenile idiopathic arthritis KW - TMJ KW - OPT KW - asymmetry KW - condyle pathomorphology Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325882 VL - 14 ER - TY - JOUR A1 - Sauer, Alexander A1 - Li, Mengxia A1 - Holl-Wieden, Annette A1 - Pabst, Thomas A1 - Neubauer, Henning T1 - Readout-segmented multi-shot diffusion-weighted MRI of the knee joint in patients with juvenile idiopathic arthritis JF - Pediatric Rheumatology N2 - Background: Diffusion-weighted MRI has been proposed as a new technique for imaging synovitis without intravenous contrast application. We investigated diagnostic utility of multi-shot readout-segmented diffusion-weighted MRI (multi-shot DWI) for synovial imaging of the knee joint in patients with juvenile idiopathic arthritis (JIA). Methods: Thirty-two consecutive patients with confirmed or suspected JIA (21 girls, median age 13 years) underwent routine 1.5 T MRI with contrast-enhanced T1w imaging (contrast-enhanced MRI) and with multi-shot DWI (RESOLVE, b-values 0–50 and 800 s/mm\(^2\)). Contrast-enhanced MRI, representing the diagnostic standard, and diffusion-weighted images at b = 800 s/mm\(^2\) were separately rated by three independent blinded readers at different levels of expertise for the presence and the degree of synovitis on a modified 5-item Likert scale along with the level of subjective diagnostic confidence. Results: Fourteen (44%) patients had active synovitis and joint effusion, nine (28%) patients showed mild synovial enhancement not qualifying for arthritis and another nine (28%) patients had no synovial signal alterations on contrast-enhanced imaging. Ratings by the 1st reader on contrast-enhanced MRI and on DWI showed substantial agreement (κ = 0.74). Inter-observer-agreement was high for diagnosing, or ruling out, active arthritis of the knee joint on contrast-enhanced MRI and on DWI, showing full agreement between 1st and 2nd reader and disagreement in one case (3%) between 1st and 3rd reader. In contrast, ratings in cases of absent vs. little synovial inflammation were markedly inconsistent on DWI. Diagnostic confidence was lower on DWI, compared to contrast-enhanced imaging. Conclusion: Multi-shot DWI of the knee joint is feasible in routine imaging and reliably diagnoses, or rules out, active arthritis of the knee joint in paediatric patients without the need of gadolinium-based i.v. contrast injection. Possibly due to “T2w shine-through” artifacts, DWI does not reliably differentiate non-inflamed joints from knee joints with mild synovial irritation. KW - diffusion-weighted MRI KW - juvenile idiopathic arthritis KW - synovitis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158095 VL - 15 IS - 73 ER - TY - JOUR A1 - Eberhardt, Christiane S. A1 - Haas, Johannes-Peter A1 - Girschick, Hermann A1 - Schwarz, Tobias A1 - Morbach, Henner A1 - Rösen-Wolff, Angela A1 - Foell, Dirk A1 - Dannecker, Guenther A1 - Schepp, Carsten A1 - Ganser, Gerd A1 - Honke, Nora A1 - Eggermann, Thomas A1 - Müller-Berghaus, Jan A1 - Wagner, Norbert A1 - Ohl, Kim A1 - Tenbrock, Klaus T1 - No association of IL-12p40 pro1.1 polymorphism with juvenile idiopathic arthritis JF - Pediatric Rheumatology N2 - Background: IL-12p40 plays an important role in the activation of the T-cell lines like Th17 and Th1-cells. Theses cells are crucial in the pathogenesis of juvenile idiopathic arthritis. A polymorphism in its promoter region and the genotype IL12p40 pro1.1 leads to a higher production of IL-12p40. We studied whether there is a difference in the distribution of the genotype in patients with JIA and the healthy population. Methods: In 883 patients and 321 healthy controls the IL-12p40 promoter genotype was identified by ARMS-PCR. Results: There is no association of IL-12p40 pro polymorphism neither in patients with JIA compared to controls nor in subtypes of JIA compared to oligoarthritis. We found a non-significant tendency of a higher prevalence of the genotype pro1.1 in systemic arthritis (32.4 %) and in rheumatoid factor negative polyarthritis (30.5 %) and a lower pro1.1 genotype in persistent oligoarthritis (20.7 %) and in enthesitis-related arthritis (17 %). Likelihood of the occurrence of genotype IL12-p40 pro1.1 in patients with systemic arthritis (OR 1.722, CI 95 % 1.344-2.615, p 0.0129) and RF-negative polyarthritis (OR 1.576, CI 95 % 1.046-2.376, p 0.0367) compared to persistent oligoarthritis was significantly higher. This was also true for comparison of their homozygous genotypes IL-12p40 pro 1.1 and 2.2 in systemic arthritis (OR 1.779, CI 95 % 1.045-3.029, p 0.0338). However, in Bonferroni correction for multiple hypothesis this was not significant. Conclusion: A tendency of a higher prevalence of the genotype IL-12p40 pro1.1 in systemic arthritis and in rheumatoid factor negative polyarthritis was observed but not significant. Further investigations should be done to clarify the role IL-12p40 in the different subtypes of JIA. KW - polymorphism KW - cytokine KW - children KW - serum KW - IL12B KW - gene KW - cells KW - juvenile idiopathic arthritis KW - IL-12p40 KW - IL-12B KW - promoter Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136281 VL - 13 IS - 61 ER -