更新于：2024-11-01

DR4 x DR1

更新于：2024-11-01

基本信息

关联

项与 DR4 x DR1 相关的药物

DR1/DR4 program (Provid Pharma)

靶点

DR1 x DR4

作用机制

DR1 inhibitors [+1]

在研机构

Provid Pharmaceuticals, Inc.

原研机构

Provid Pharmaceuticals, Inc.

在研适应症

类风湿关节炎

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 DR4 x DR1 相关的临床结果

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100 项与 DR4 x DR1 相关的转化医学

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0 项与 DR4 x DR1 相关的专利（医药）

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384

项与 DR4 x DR1 相关的文献（医药）

2024-02-01·Veterinary Parasitology

Genetic variability of Dirofilaria repens isolates from humans and dogs in Italy

Article

作者: Veronesi, Fabrizia ; Brustenga, Leonardo ; Ciuca, Lavinia ; Sforna, Monica ; Barlozzari, Giulia ; Orlandi, Margherita ; Rigamonti, Giulia ; Morganti, Giulia ; Gabrielli, Simona

Dirofilaria repens is a paradigmatic example of an emerging vector-borne pathogen (VBP) in both human and veterinary fields. The spatial expansion and the increasing zoonotic impact of this VBP can be related to several drivers including the genetic structure of parasite populations. Italy is one of the European countries traditionally endemic with the highest incidence of canine and human cases of subcutaneous dirofilariosis. The present study aimed to assess the genetic identity and variability of D. repens isolates of human and canine origin from areas of Central Italy, compared with those isolated from different areas of Europe by sequence analysis of mtDNA genes (i.e., 12 S rDNA and cox1). A total of twenty isolates of D. repens were obtained from biopsies of subcutaneous and ocular cases of dirofilariosis occurring in 10 dogs and 10 humans. The sequence analysis of 12 S rDNA showed that all the sequences obtained clustered as a monophyletic group with a strong nodal support, indicating that all sequence types represented D. repens. The cox1 and the 12 S sequence analysis did not show host-related polymorphisms between human and dog-derived specimens. The sequence analysis of cox1 was performed including 8 additional sequences previously obtained from human and canine isolates in the same areas. Out of the 28 sequences analyzed, 20 were grouped in a haplogroup comprising 15 haplotypes (i.e., DR1, DR2, DR4, DR5, DR7, DR8, DR10-DR18), 2 sequences matched to DR9, reported for the first time in Italy, and 6 showed peculiar polymorphisms that were not previously described. The results obtained have implications for a better understanding of the epidemiology and phylogeography of this emerging vector-borne zoonotic parasite.

2023-10-01·World Journal of Pediatrics

Human bocavirus 1 and 2 genotype-specific antibodies for rapid antigen testing in pediatric patients with acute respiratory infections

Article

作者: Qin, Cheng-Feng ; Zhao, Lin-Qing ; Wang, Fang ; Jia, Li-Ping ; De, Ri ; Zhou, Yu-Tong ; Sun, Yu ; Liu, Li-Ying ; Zhao, Hui ; Zhu, Ru-Nan ; Dong, Hui-Jin ; Xu, Yan-Peng ; Shi, Pan-Deng

BACKGROUNDPrevious serological studies of human bocavirus (HBoV) 1 could not exclude cross-reactivity with the other three HBoVs, particularly HBoV2.METHODSTo search for genotype-specific antibodies against HBoV1 and HBoV2, the divergent regions (DRs) located on the major capsid protein VP3 were defined through viral amino acid alignment and structure prediction. DR-deduced peptides were used as antigens to harvest corresponding anti-DR rabbit sera. To determine their genotype specificities for HBoV1 and HBoV2, these sera samples were used as antibodies against the antigens VP3 of HBoV1 and HBoV2 (expressed in Escherichia coli) in western blotting (WB), enzyme-linked immunosorbent assay (ELISA), and bio-layer interferometry (BLI) assays. Subsequently, the antibodies were evaluated with clinical specimens from pediatric patients with acute respiratory tract infection by indirect immunofluorescence assay (IFA).RESULTSThere were four DRs (DR1-4) located on VP3 with different secondary and tertiary structures between HBoV1 and HBoV2. Regarding the reactivity with VP3 of HBoV1 or HBoV2 in WB and ELISA, high intra-genotype cross-reactivity of anti-HBoV1 or HBoV2 DR1, DR3, and DR4, but not anti-DR2, was observed. Genotype-specific binding capacity of anti-DR2 sera was confirmed by BLI and IFA, in which only anti-HBoV1 DR2 antibody reacted with HBoV1-positive respiratory specimens.CONCLUSIONAntibodies against DR2, located on VP3 of HBoV1 or HBoV2, were genotype specific for HBoV1 and HBoV2, respectively.

2023-07-01·HLA

Complete sequences of six major histocompatibility complex haplotypes, including all the major MHC class II structures.

Article

作者: Henrich, Birgit ; Le, Duyen B ; Scholz, Stephan ; Strelow, Daniel ; Palmer, William H ; Belick, Dana ; Wachtmeister, Thorsten ; Hülse, Lisanna ; Pollock, Nicholas R ; Parham, Peter ; Lautwein, Tobias ; Wollenweber, Tassilo E ; Dilthey, Alexander T ; Köhrer, Karl ; Houwaart, Torsten ; Norman, Paul J ; Kichula, Katherine M ; Guethlein, Lisbeth A

Accurate and comprehensive immunogenetic reference panels are key to the successful implementation of population-scale immunogenomics. The 5Mbp Major Histocompatibility Complex (MHC) is the most polymorphic region of the human genome and associated with multiple immune-mediated diseases, transplant matching and therapy responses. Analysis of MHC genetic variation is severely complicated by complex patterns of sequence variation, linkage disequilibrium and a lack of fully resolved MHC reference haplotypes, increasing the risk of spurious findings on analyzing this medically important region. Integrating Illumina, ultra-long Nanopore, and PacBio HiFi sequencing as well as bespoke bioinformatics, we completed five of the alternative MHC reference haplotypes of the current (GRCh38/hg38) build of the human reference genome and added one other. The six assembled MHC haplotypes encompass the DR1 and DR4 haplotype structures in addition to the previously completed DR2 and DR3, as well as six distinct classes of the structurally variable C4 region. Analysis of the assembled haplotypes showed that MHC class II sequence structures, including repeat element positions, are generally conserved within the DR haplotype supergroups, and that sequence diversity peaks in three regions around HLA-A, HLA-B+C, and the HLA class II genes. Demonstrating the potential for improved short-read analysis, the number of proper read pairs recruited to the MHC was found to be increased by 0.06%-0.49% in a 1000 Genomes Project read remapping experiment with seven diverse samples. Furthermore, the assembled haplotypes can serve as references for the community and provide the basis of a structurally accurate genotyping graph of the complete MHC region.