PubMed · 6951353
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
D O White. 1981. Recent developments in virology.. https://pubmed.ncbi.nlm.nih.gov/6951353/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Head and neck cancer in advanced stages are difficult to treat. Therefore, development of new treatment modalities and preventive measures are required. We now report the identification of human head and neck cancer antigens recognized by the humoral immune system. We used the serological analysis of recombinant cDNA expression libraries (SEREX) approach. cDNA libraries from cell lines of squamous cell carcinoma of head and neck (SCCHN) and a normal testicle tissue were screened using sera from six allogeneic SCCHN patients. Total 28 positive clones belonging to 19 different genes were identified, including 12 known genes and 7 unknown ones. Expression analysis on 13 normal tissues and 13 cancer tissues using reverse transcription-PCR (RT-PCR) revealed eight ubiquitously expressed genes, nine of which were expressed preferentially in cancer tissues and two cancer/testis antigens. These antigens we defined may be pertinent candidate antigens for future cancer-diagnosis and related immunotherapy.
We have studied the relationship between diabetes-associated autoantibodies and various HLA genotypes and alleles in patients with newly diagnosed type 1 diabetes, in non-diabetic siblings and in children representing the general population to test the hypothesis that specific HLA genes regulate the humoral immune response to various autoantigens. Among the newly diagnosed patients we observed that those carrying the DR4-DQB1*0302 haplotype had increased levels of insulin autoantibodies (IAA) and IA-2 antibodies (IA-2A), but low levels of GAD antibodies (GADA). In contrast, those with the DR3-DQB1*02 haplotype had increased GADA titers but low IAA and IA-2 levels. DQB1*02-homozygous patients had a conspicuously low frequency and low levels of IA-2A. Among the siblings there was an apparent association between genetic risk and the prevalence of islet cell antibodies (ICA), IAA, GADA, IA-2A and multiple autoantibodies, the latter being detectable at a frequency of 24.1% in high risk siblings and at a frequency of only 0.9% in those with genotypes conferring disease protection. Among 7-16-year-old Finnish schoolchildren there was an association between GADA and the DQB1*02/*0302 genotype and the DQB1*0302 allele. Among young children identified from the general population based on high (DQB1*02/0302 heterozygosity) or moderate (DQB1*0302/x; x not equal *02, *0301, *0602, *0603) genetic risk for type 1 diabetes the high risk children seroconverted more often to positivity for ICA, GADA and IA-2A over their first 2 years of life. Among older sibs of these children we observed an obvious relationship between the degree of genetic risk and the frequency of ICA, IAA, GADA, IA-2A, and multiple antibodies. Taken together these observations suggest that HLA genes have a strong impact on the appearance of diabetes-associated autoantibodies both in first-degree relatives of affected children and in the general population. In patients with newly diagnosed disease IA-2A may be a more specific marker of beta-cell damage, whereas GADA might reflect a propensity to autoimmunity in general.
Autoantibodies directed against nucleic acid and protein complexes present in cell nuclei characterize autoimmune diseases and are employed in diagnosis. The mechanisms by which these autoantigens escape immunological tolerance are largely unknown, but a number of recent observations suggest that modified self-protein generated during apoptosis my play an important part in the development of autoimmunity. To investigate the possibility that autoantibodies in patients with Sjögren's syndrome are induced by apoptosis and presented on the surface of the cell, the internal distribution of autoantigens in apoptotic human salivary gland cells was studied in vitro. Salivary gland cells were treated with tumour necrosis factor-alpha, an apoptosis inducer. At increasing times after induction, cells were homogenized and cytoplasmic, cell surface membrane and nuclear compartments were fractionated using a sucrose density-gradient system. Autoantigens alpha-fodrin, SS-A (Ro), SS-B (La), and the enzyme poly(ADP-ribose) polymerase, were detected by conventional immunofluorescence and confirmed by Western immunoblotting. At increasing times after apoptosis, nuclear proteins SS-A (Ro) and SS-B (La), but not poly(ADP-ribose) polymerase were relocated from the cell nucleus to the cell surface membrane. Fodrin, a cytoplasmic protein, was also translocated to the cell membrane after cleavage of alpha-fodrin. These results show that autoantigens fodrin, SS-A (Ro) and SS-B (La) in human salivary gland cells undergo a striking redistribution during apoptosis and relocate to the cell membrane of apoptotic cells. The appearance of autoantigens on the surface of induced cells could form the basis of a mechanism for autoantigen presentation, processing and autoantibody induction.