myelin-basic-protein and Dermatitis--Atopic

Topics: Alkaline Phosphatase; B-Lymphocytes; Carcinoembryonic Antigen; Cytoskeleton; Dermatitis, Atopic; Humans; Immunoenzyme Techniques; Immunoglobulins; Langerhans Cells; Lectins; Microscopy, Electron; Myelin Basic Protein; Neoplasms, Nerve Tissue; Nerve Tissue Proteins; Papillomaviridae; Peanut Agglutinin; Plant Lectins; Skin Diseases; Skin Neoplasms; T-Lymphocytes; Tumor Virus Infections

In this study, we investigated the changes in global methylation status and its functional relevance in childhood atopic dermatitis (AD). Differences in epigenome-scale methylation events in peripheral blood associated with childhood AD were screened using DNA methylation arrays of 24 patients with AD compared with 24 control subjects. Of the 16,840 differentially methylated CpG regions between AD and control subjects, >97% CpG loci revealed hypomethylation in patients with childhood AD. Among the globally hypomethylated loci, we identified two CpG clusters within the golli-mbp locus of the MBP gene, which was functionally enriched by subnetwork enrichment analysis as an orchestrator among associated genes. The differential hypomethylation of the top-ranked cg24700313 cluster in the golli-mbp locus was validated by pyrosequencing in an independent cohort of 224 children with AD and 44 control subjects. DNA methylation was found to be negatively correlated with disease severity but showed no significant correlation with IgE levels after age adjustment. The multivariate correlation analysis represents a higher score in AD intensity with significantly increased IgE levels and decreased methylation levels in cg27400313. We concluded that methylation loss in the golli-mbp locus is an epigenetic factor associated with disease severity of childhood AD.

Topics: Biomarkers; Child, Preschool; Cohort Studies; CpG Islands; Dermatitis, Atopic; DNA Methylation; Epigenesis, Genetic; Female; High-Throughput Nucleotide Sequencing; Humans; Immunoglobulin E; Male; Myelin Basic Protein; Severity of Illness Index; Tissue Array Analysis

Lines of rat T lymphocytes responsive to the basic protein of myelin (BP) or to the purified protein derivative of Mycobacterium tuberculosis (PPD) were inoculated i.v. into recipient rats. As reported previously, the anti-BP line cells, but not the anti-PPD line cells spontaneously accumulated in the central nervous system and caused encephalomyelitis. However, the anti-PPD line cells could be induced to enter the brain and cause bystander encephalitis by intracerebral inoculation of PPD. Anti-PPD or anti-BP line cells could mediate delayed-type hypersensitivity skin reactions or bystander arthritis elicited by specific antigen. The lines did not cause specific cytolysis in vitro. Susceptibility to delayed-type hypersensitivity or bystander disease was long lasting in rats inoculated with anti-PPD line cells, while rats inoculated with anti-BP line cells were susceptible for only a few days. Thus, lines of T lymphocytes can mediate a variety of pathological reactions directed by the presence of specific antigen, self or foreign.

Topics: Animals; Arthritis; Cell Line; Cytotoxicity, Immunologic; Dermatitis, Atopic; Encephalitis; Encephalomyelitis, Autoimmune, Experimental; Female; Hypersensitivity, Delayed; Injections, Intradermal; Macrophages; Male; Myelin Basic Protein; Rats; Rats, Inbred Lew; Skin Tests; T-Lymphocytes; Tuberculin