Riassunto analitico
Membranous Nephropathy (MN) represents a large amount of Nephrotic Syndromes in the adult population and its definitive diagnosis is currently carried out through biopsy. An autoimmune condition has been demonstrated in idiopathic MN (iMN) in which some kidney structures are targeted by patient autoantibodies. We know that not all of target proteins involved and responsible for the disease are known yet. One of the most important discoveries in the last decade was the understanding of the possible mechanisms of disease development by the identification of the M-type phospholipase A2 receptor (PLA2R) as the target antigen of autoantibodies in idiopathic MN (iMN). Anti-PLA2R autoantibodies are highly specific for iMN and are found in the serum of approx. 75% of iMN patients at time of diagnosis. In patients with secondary MN or in healthy individuals, anti-PLA2R antibodies only occur rarely. In this work our aim is to identify new proteins by screening a lambda-phage library with patients’ sera. A commercial cDNA phagemide library was screened using the above described sera, in order to detect positive signals due to antigen-antibody bond. We detected one phagemide clone expressing a new autoantigen: Synaptonemal Complex protein 65 (SC65). By testing a large amount of patients sera, in order to assay the ratio of serum antibodies against PLA2R and the newly discovered SC65, we had the possibility to say what is the test prediction to diagnose MN from just serum, avoiding the more invasive procedure of renal biopsy.
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Abstract
Membranous Nephropathy (MN) represents a large amount of Nephrotic Syndromes in the adult population and its definitive diagnosis is currently carried out through biopsy. An autoimmune condition has been demonstrated in idiopathic MN (iMN) in which some kidney structures are targeted by patient autoantibodies. We know that not all of target proteins involved and responsible for the disease are known yet. One of the most important discoveries in the last decade was the understanding of the possible mechanisms of disease development by the identification of the M-type phospholipase A2 receptor (PLA2R) as the target antigen of autoantibodies in idiopathic MN (iMN). Anti-PLA2R autoantibodies are highly specific for iMN and are found in the serum of approx. 75% of iMN patients at time of diagnosis. In patients with secondary MN or in healthy individuals, anti-PLA2R antibodies only occur rarely.
In this work our aim is to identify new proteins by screening a lambda-phage library with patients’ sera. A commercial cDNA phagemide library was screened using the above described sera, in order to detect positive signals due to antigen-antibody bond. We detected one phagemide clone expressing a new autoantigen: Synaptonemal Complex protein 65 (SC65).
By testing a large amount of patients sera, in order to assay the ratio of serum antibodies against PLA2R and the newly discovered SC65, we had the possibility to say what is the test prediction to diagnose MN from just serum, avoiding the more invasive procedure of renal biopsy.
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