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  - 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  -