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FIG 3


AUTOANTIBODIES AGAINST DESMOGLEIN 1 DETECTED BY CELL-BASED IIFT


in incidence over the last 20 years. Autoantibodies against exocrine pancreas have long been known to be specific markers for Crohn’s disease. But it is only recently that two autoantigenic targets have been identified, namely CUZD1 and GP2. This has paved the way for the development of cell-based IIFT systems to detect the corresponding autoantibodies. In a comparative study the cell-based


FIG 4


AUTOANTIBODIES AGAINST NMDA RECEPTORS DETECTED BY CELL-BASED IIFT


anti-CUZD1 and anti-GP2 assays proved to be more efficient for detecting anti-exocrine pancreas antibodies than traditionally used sections of human pancreas. More sera were identified with the cell-based substrates than with the tissue, and discrimination between positive and negative results was generally easier. In total, anti-CUZD1 and anti-GP2 autoantibodies were detected in 34 of 96 patients (35.4%) with Crohn’s disease and in three of 39 patients with ulcerative colitis (7.7%), demonstrating the usefulness of these tests in the diagnosis of chronic inflammatory bowel diseases.


AUTOIMMUNE ENCEPHALOPATHIES Several new autoantibody parameters for the diagnosis of autoimmune encephalopathies can now be determined routinely thanks to cell-based IIFT systems. These include autoantibodies against glutamate receptors of type N-methyl-D- aspartate (NMDA), glutamate receptors of type AMPA, GABA receptors B1, contactin- associated protein 2 (CASPR2) and leucine- rich glioma-inactivated protein 1 (LGI1). The anti-NMDAR test system, in


particular, has proven extremely valuable in diagnosing cases of autoimmune anti- NMDA receptor encephalitis (figure 4). This considerably under-diagnosed disease manifests with severe psychotic symptoms. It frequently affects women with ovarian teratoma, but is also now increasingly identified in other patient groups. Early diagnosis is crucial since patients often improve with immunotherapy and tumour removal. In a clinical study the test demonstrated a very high efficiency for detection of anti- NMDAR autoantibodies, thus confirming its diagnostic value for neurologists.


CROHN’S DISEASE Crohn’s disease is a chronic inflammatory bowel disease, which has increased


28 www.lifesciencesmagazines.com


IDIOPATHIC MEMBRANOUS NEPHROPATHY Autoantibodies against phospholipase A2 receptors (PLA2R) have recently been identified as triggers of the autoimmune reaction involved in idiopathic membranous nephropathy (IMN), a chronic inflammatory disease of the glomeruli which is accompanied by an increasing reduction in kidney function. They are highly specific


for IMN and occur in the serum of 70% of patients. The method of choice (gold standard) for their detection is a new IIFT based on cells transfected with constructs expressing PLA2R, which provide highly sensitive and specific antibody detection. Serological screening for anti-PLA2R


autoantibodies supplements invasive diagnostic methods such as kidney puncture, histological examination or electron microscopy of kidney tissue and is also suitable for assessing the response to therapy.


CONCLUSION Indirect immunofluorescence assays based on transfected cells represent a new technology for antibody diagnostics. A host of cell-based immunoassays based on freshly identified target antigens has already enriched the serological diagnosis of numerous autoimmune diseases. The assay technology is also employed in infectious disease diagnostics, for example, in the detection of antibodies against Crimean- Congo fever virus. Significantly, the new technology can be applied to virtually any antigen. Since new target antigens are being identified and characterised at a prodigious rate, cell-based immunoassays are certain to play an important role in serological diagnostics of the future. ■


ML


 REFERENCES References available on request (magazine@informa.com)


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