Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial cells are suspected of being the target of autoimmune processes seen in many connective tissue diseases and in systemic vasculitis as evidenced by the detection of circulating autoantibodies against endothelial cell antigens. In order to select B cells recognizing endothelial cells antigens, Epstein-Barr virus (EBV)-infected B cells, obtained from one patient presenting a systemic vasculitis, were cocultured with human endothelial cells concurrently with a human endothelial cell line (EC-pSV1 cells). This coculture consisted of a first step of expansion of B cells specifically selected by adherence onto human umbilical vein endothelial cells (HUVEC). The adherence of selected B cells was specific to endothelial cells because no rosette formation around control cells (HeLa cells or COS cells) was observed. Adherent B cells were cloned by limiting dilution by coculture onto EC-pSV1 cells and screened for anti-HUVEC antibody production by endothelial cell ELISA. An increase in anti-HUVEC antibody production of IgM isotype was detected by endothelial cell ELISA, peaking at Day 9 and remaining constantly elevated, relative to B cell expansion. Among 21 B cell lines producing IgM, 6 presented high levels of anti-HUVEC antibodies, whereas 1 of 52 B cells cloned without EC-pSV1 cells showed such antibody production. Anti-HUVEC antibody production and B cell proliferation were dependent on the presence of endothelial cells. Two of these 6 B cell lines produced antibodies directed against an endothelial cell antigen with an apparent molecular weight of 192 kDa as determined by immunoblotting analysis. Our results demonstrate that adherence of EBV-infected B cells to endothelial cells and further cloning by adherence can efficiently select anti-HUVEC antibody-producing human B cells and might help to define antigens potentially involved in autoimmune diseases.
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PMID:Production of anti-endothelial cell antibodies by coculture of EBV-infected human B cells with endothelial cells. 768 68

We previously generated a rat model that developed systemic connective tissue diseases, including synovitis, myositis, and small-vessel vasculitis (SVV), and established a vascular endothelial cell-reactive T-cell clone, VASC-1, from the model. VASC-1 was determined to be a type II natural killer T-cell clone. In this study, we attempted to identify the antigen recognized by VASC-1. The monkey-derived cell line COS-7 was used because VASC-1 does not bind naturally to COS-7, although the amino acid sequences are well conserved between monkey CD1d and rat CD1d. We generated 98 COS-7 clones transfected with miscellaneous rat cDNA and screened them for VASC-1 binding. Consequently, we found one clone, 4D2, which could bind to VASC-1. Sequencing identified the rat cDNA introduced into 4D2 as sterol carrier protein 2 (SCP2). When VASC-1 was co-cultured with SCP2 knockdown rat vascular endothelial cells, VASC-1 binding was reduced significantly. Moreover, we designed a series of rat SCP2 peptides and introduced them into COS-7 cells. On the basis of VASC-1 binding and proliferation, we revealed that the peptide rSCP2518-532 included the epitope recognized by VASC-1. Furthermore, immunization with rSCP2518-532 accelerated the development of SVV in the rat model. The collective findings suggest that type II natural killer T cells reactive with autologous SCP2 are implicated in vascular inflammation in the rat model.
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PMID:Type II Natural Killer T Cells that Recognize Sterol Carrier Protein 2 Are Implicated in Vascular Inflammation in the Rat Model of Systemic Connective Tissue Diseases. 2786 14