scholarly journals Monoclonal anti‐dsDNA antibody 2C10 escorts DNA to intracellular DNA sensors in normal mononuclear cells and stimulates secretion of multiple cytokines implicated in lupus pathogenesis

2019 ◽  
Vol 199 (2) ◽  
pp. 150-162 ◽  
Author(s):  
K. Inoue ◽  
M. Ishizawa ◽  
T. Kubota

2021 ◽  
Vol 12 ◽  
Author(s):  
Annika Wiedemann ◽  
Marie Lettau ◽  
Sarah Y. Weißenberg ◽  
Ana-Luisa Stefanski ◽  
Eva-Vanessa Schrezenmeier ◽  
...  

B- and T-lymphocyte attenuator (BTLA/CD272) is an inhibitory checkpoint molecule expressed on T and B cells. Prior studies reported defective function of BTLA by T cells in patients with systemic lupus erythematosus (SLE), whereas nothing is known about its role on B cells in SLE, a disease with various B cell abnormalities. Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors (HD) and 34 SLE patients were stained for BTLA and its expression on B cells was assessed. PBMCs or CD27-IgD+ naive B cells were stimulated together with an activating anti-BTLA antibody or an inhibitor of spleen tyrosine kinase (SYK) and differentiation as well as the expression of activation markers CD71, PD-1 and CD86 were analyzed. Our phenotypic and functional studies revealed reduced BTLA expression on CD27-IgD+ naïve B cells from SLE patients (p=0.0017) related to anti-dsDNA antibody titers (p=0.0394) and SIGLEC-1/CD169 expression on monocytes (p=0.0196), a type I interferon marker related to disease activity. BTLA engagement was found to control CpG/TLR9 activation limiting plasmablast (p=0.0156) and B cell memory induction (p=0.0078) in normal B cells in contrast to other B cell activation pathways (CD40, BCR). These BTLA functions were impaired in SLE B cells. Inhibition of SYK was found to mimic the effects of BTLA activity in vitro. Thus, is it possible that reduced BTLA expression and function of CD27-IgD+ antigen- and T cell-inexperienced SLE B cells could be overcome by SYK inhibition which should be tested in future studies as potential therapeutic principle.



Author(s):  
S. Siew ◽  
W. deMendonca-Calaca

A 36 year old man presented with a mass in the chest and multiple “hot” focal lesions were identified on bone scan. Fine needle aspiration was performed of the chest mass. Routine histology showed the presence of some bundles of dense fibrous tissue and a diffuse infiltration of mononuclear cells, which varied in size and nucleo-cytoplasmic ratio. The smaller cells had eccentric hyperchromatic nuclei. Nucleoli were noted in the larger cells. There was well marked cytoplasmic vacuolation of some of the cells. Mitosis was present. A small fragment of tissue was received for electron microscopy. Examination of 1 μm sections showed trabeculae of medium-large polygonal cells with eccentric nuclei and occasional nucleoli. Some irregularly shaped cells had well marked cytoplasmic vacuolation. Mitotic figures were present.





VASA ◽  
2014 ◽  
Vol 43 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Weibin Huang ◽  
Weiwei Qin ◽  
Lei Lv ◽  
Haoyv Deng ◽  
Hao Zhang ◽  
...  

Background: Duffy antigen / receptor for chemokines (DARC) possesses high affinity for several chemokine subgroups of CC and CXC. Although DARC has been shown to play a role in many inflammatory diseases, its effect on chronic venous disease (CVD) remains unidentified. We explored whether the expression of DARC in skin tissue was activated under venous hypertension as well as the relationships between DARC and inflammation. Materials and methods: The inflammation in a rat model of venous hypertension caused by a femoral arterial-venous fistula (AVF) was studied. At specified intervals the pressure in the femoral veins was recorded within 42 days. Hindlimb skin specimens were harvested at different time points. The expressions of DARC, interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) in skin tissue were examined. Mononuclear cells infiltrated in skin tissue were detected. Results: Femoral venous pressures in AVF groups increased significantly at different time points (P < 0.01). DARC was expressed in skin tissue and its expression level increased significantly in AVF groups from the 7nd day on and was enhanced in a time-dependent manner within 42 days (P < 0.05). Meanwhile, both MCP-1 and IL-8 had higher levels, accompanied by increased mononuclear cells infiltrating into skin tissue (P < 0.05). Conclusions: A rat AVF model which can maintain venous hypertension for at least 42 days is competent for researching the pathogenesis of CVD. DARC, which plays a role in the inflammation of skin tissue under venous hypertension, may become a new molecular target for diagnosis and treatment of CVD at a very early stage.



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