IMMUNOPRINTING EXCLUDES MANY POTENTIAL SUSCEPTIBILITY GENES AS PREDISPOSING TO EARLY-ONSET PAUCIARTICULAR JUVENILE CHRONIC ARTHRITIS EXCEPT HLA CLASS-II AND TNF
EUROPEAN JOURNAL OF IMMUNOGENETICS
Authors: EPPLEN, C; RUMPF, H; ALBERT, E; HAAS, P; TRUCKENBRODT, H; EPPLEN, JT
Abstract
DNA profiles (immunoprints) were generated for 120 patients suffering from early onset pauciarticular chronic arthritis (EOPA-JCA) and >500 healthy controls utilizing highly polymorphic microsatellites in the vicinity of immunorelevant genes. Six T cell receptor (TCR) markers for the CD3D, TCRDVAJ, TEA, TCRBV6S1, BV6S3, BV6S7 and BV13S2 genes were analysed. Furthermore markers for the cell surface molecule CD40L, for cytokine genes (IL-1A, IL-2, IFN-alpha, FGF-alpha, TNF-alpha), the chromosomal region of the IRF2 and the cytokine receptor gene IL5RA were studied as well as two polymorphisms within the promotor region of the TNF-alpha gene. Coding region polymorphisms were evidenced indirectly by repeat length variation or they were predicted from the microsatellite distribution profiles and then confirmed by direct sequence analysis. Statistical evaluations were performed with respect to known predispositions, predominance of females (>80%) and HLA-DR and -DQ haplotypes. Cell surface molecules (TCR, CD40L, IL5RA) as well as almost all cytokines (IL-1A, IFN alpha, FGFA, IRF2 region) were excluded as predisposing in our JCA panel. The TNF-alpha microsatellite alleles (GT)(10-12) contribute considerably to manifestation of the disease, in HLA-DRB1*11(12) individuals (RR = 12.8). The TNF-alpha allele is not found in linkage disequilibrium with HLA-DRB1*11(12) and may be present on either chromosome 6. Thus, a novel susceptibility factor probably within the TNFA/TNFB gene region has been identified via linkage with the TNF-alpha microsatellite allele. Apparently complex compositions of the genetic background rather than single genes provide the precondition for manifestation of the autoimmune disease EOPA-JCA. Immunoprinting unravels the variability of the immunological genome via the semi-directed microsatellite approach efficiently.
LCK as a Potential Therapeutic Target for Acute Rejection after Kidney Transplantation: A Bioinformatics Clue
JOURNAL OF IMMUNOLOGY RESEARCH
Authors: Jia, Linpei; Jia, Rufu; Li, Yinping; Li, Xiaoxia; Jia, Qiang; Zhang, Hongliang
Abstract
Objectives. We aim to identify the key biomarker of acute rejection (AR) after kidney transplantation via bioinformatics methods. Methods. The gene expression data GSE75693 of 30 samples with stable kidney transplantation recipients and 15 AR samples were downloaded and analyzed by the limma package to identify differentially expressed genes (DEGs). Then, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were done to explore the biological functions and potential important pathways of DEGs. Finally, protein-protein interactions (PPIs) and literature mining were applied to construct the cocitation network and to select the hub protein. Results. A total of 437 upregulated genes and 353 downregulated genes were selected according to P < 0 01 and log(2) fold change > 1 0. DEGs of AR are mainly located on membranes and impact the activation of receptors in immune responses. In the PPI network, Src kinase, lymphocyte kinase (LCK), CD3G, B2M, interferon-gamma, CD3D, tumor necrosis factor, VAV1, and CD3E in the T cell receptor signaling pathway were selected as important factors, and LCK was identified as the hub protein. Conclusion. LCK, via acting on T-cell receptor, might be a potential therapeutic target for AR after kidney transplantation.