Disease relevance of ICA1

• 5'-RNA ligase-mediated rapid amplification of cDNA ends evaluation of ICA1 transcripts expressed in human islets, testis, heart, and cultured neuroblastoma cells reveals that three 5'-untranslated region exons are variably expressed from the ICA1 gene in a tissue-specific manner [1].
• Primary Sjögren's syndrome and deficiency of ICA69 [2].
• Islet cell autoantigen 69 kDa (ICA69) has been reported as a polypeptide antigen expressed in pancreatic beta cells, and autoimmunity against this antigen has been associated with insulin-dependent diabetes mellitus [3].
• None of the patients with autoimmune thyroid disease (n = 20), inflammatory bowel disease (n = 9) or multiple sclerosis (n = 7) had elevated ICA69 antibodies [4].
• Type 1, or insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease associated with loss of tolerance to several pancreatic islet cell molecules, including insulin, glutamic acid decarboxylase (GAD), ICA69 and the tyrosine phosphatase IA-2 (refs 1-3) [5].

High impact information on ICA1

• We show that during fetal development and childhood, mRNAs for insulin and other islet cell autoantigens (GAD, ICA69, IA-2) are expressed at low levels in the human thymus [5].
• In healthy NOD mice, ICA69-specific T cells accumulated in lymph nodes that drain salivary tissue [2].
• We aimed to assess the role of ICA69 in autoimmunity against Sjögren's syndrome [2].
• INTERPRETATION: ICA69 is a new autoantigen in primary Sjögren's syndrome that has an important role in progression of disease and could be of diagnostic value [2].
• ICA69 autoimmunity was investigated in controls and in patients with primary Sjögren's syndrome or systemic lupus erythematosus, and in various NOD mice, some of which were given an ICA69-directed prototype peptide vaccine [2].

Chemical compound and disease context of ICA1

• The mRNAs for the intermediate isoforms (p69) of human 2',5'-oligoadenylate synthetase are rapidly induced 10- to 20-fold in HT1080 glioma cells by IFN-beta and induced 3-fold at 24 h by IFN-gamma [6].

Biological context of ICA1

• On the basis of the nucleotide sequences, three different scFvs were obtained (ICA1, ICB7, and ICA5) [7].
• Pancreatic ICA69 expression increased with age, adult levels being five times higher than the levels present at 13 weeks of gestation [3].
• We have studied the cell type specificity and ontogeny of ICA69 gene expression in man [3].
• ICA69 antibodies were determined by Western blot using an affinity purified recombinant fusion protein of ICA69 and maltose binding protein [4].
• Here we describe a human genomic p69 fragment which allowed us to map the gene (ICA1) to chromosome 7p22 [8].

Anatomical context of ICA1

• Islet cell autoantigen 69-kDa (ICA69), protein product of the human ICA1 gene, is one target of the immune processes defining the pathogenesis of Type 1 diabetes [1].
• Mutation of a CREB site within the ICA1 exon B promoter significantly enhances transcriptional activity in both cell lines [1].
• FINDINGS: Disruption of the ICA69 locus prevented lacrimal gland disease and greatly reduced salivary gland disease in NOD mice [2].
• T-cell and B-cell autoreactivity against ICA69 was much the same in patients with primary Sjögren's syndrome, but not in those with systemic lupus erythematosus or in healthy controls [2].
• Within the human pancreas, ICA69 is not enriched in the islets or in the beta cells [3].

Associations of ICA1 with chemical compounds

• The lower results on the NOVA 8 were adjusted upwards to match those of the ICA1 to give identical results [9].
• Total RNA from four separate preparations of isolated human islets revealed levels of ICA69 mRNA similar to those found in the pancreas as a whole, although another islet antigen, glutamic acid decarboxylase 65, was highly enriched in the islets [3].
• Using specific monoclonal and polyclonal antibodies, the induction, synthesis and subcellular localization of 69- and 100-kDa forms of 2',5'-oligoadenylate (2-5A) synthetase (p69 and p100) were investigated in alpha-interferon-treated human HeLa and Daudi cells [10].
• Taken together, the present results suggest that phosphorylation of p69 is causally involved in the control of commitment to growth in HUVE cells by acting as a coupling mechanism between surface stimuli and arachidonate pathways [11].
• IA-2, a newly isolated transmembrane protein tyrosine phosphatase, is a major islet cell autoantigen in IDDM and the precursor of a 40-kD tryptic fragment [12].

Other interactions of ICA1

• The ionised calcium concentration of sequential retentates prepared by ultrafiltration of a human control serum increased with increasing protein concentration when measured with both a Nova 2 and a Radiometer ICA1 analyser using their standard reference electrodes [13].
• Autoantibodies to the islet antigen ICA69 occur in IDDM and in rheumatoid arthritis [4].
• Human monoclonal ICA (MICA 1-6), previously derived from a DR1/DR7-positive newly diagnosed diabetic patient, recognized the islet cell autoantigen glutamate decarboxylase 65 (GAD65) and defined two distinct conformational (MICA 1/3 and MICA 4/6) and one linear (MICA 2) autoimmune epitopes in this molecule [14].
• We report some new procedures for the determination of ionized calcium using a semi-automatic ICA 1 analyser provided with a new flow-through tonometer unit, TNC 1, in connection with an automatic turntable [15].
• Serum iCa (ion selective electrode, Radiometer ICA 1), PTH (1-84 intact molecules, radioimmunoassay) and Mg (atomic absorption) were measured at birth (cord blood) and 24 hours of age [16].

Analytical, diagnostic and therapeutic context of ICA1

• Immunotherapy with a high-affinity mimicry peptide targeting ICA69-specific T-cells reduced established Sjögren's syndrome in wild-type NOD mice in the long term [2].
• ICA69 antibody quantities were determined as titres using a titration curve of a standard serum as reference [4].
• In situ hybridization and immunohistochemical staining of sections of the fetal and adult pancreas revealed expression of the ICA69 gene and protein throughout the acinar, ductal, and islet tissue, but not in the mesenchyme [3].
• Fast protein liquid chromatography purified BSA and highly purified recombinant human ICA69 were used to establish sensitive Western blot and ELISA assays in order to detect antibodies against these two proteins [17].
• We conclude that solid-phase assays are inappropriate for measurement of ICA69 antibodies as specific markers of IDDM and that antibodies to ICA69 are not detected by a liquid-phase immunoprecipitation assay [18].

References