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Charles Thirkill, Immunology; Pigment Epithelium-Derived Factor (PEDF) hypersensitivity in CAR & AMD. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2547.
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Three patients with vision loss associated with ovarian cancer were producing antibodies reactive with a 45 kd protein expressed in retina, and retinal pigment epithelium (RPE). Preliminary findings from an earlier proteomic analysis suggest the patients are reacting with RPDF, a multifunctional protein that includes control over vascular proliferations. Further research identified what appears to be the same 45 kd antibody reaction in some patients with Age-Related Macular Degenerations (AMD, a retinopathy typified by uncontrolled vascular proliferations). In light of these more recent findings, and in order to clarify any association of PEDF hypersensitivity with vision loss, a commercially obtained preparation of recombinant PEDF was incorporated into continuing immunologic inquiries
Western blot reactions confirmed the CAR and AMD patient’s antibody activity with the 45 kd protein expressed in both the retina and RPE. The patient’s antibodies were eluted from the 45 kd retina-RPE reaction site of nitrocellulose blots, and applied to a blot of recombinant RPDF; (Sigma cat # SRP 4988). Serum from normal healthy volunteers, and mouse monoclonal anti-RPDF (Millipore cat # MAB1059) was included as comparison controls.
Preliminary proteomic evidence incriminating RPDF as the 45 kd antigen is supported by findings of a corresponding reaction with the recombinant counterpart that interacts with the 45 kd reactive patient’s affinity purified antibodies. Mouse monoclonal anti-RPDF identifies the corresponding antigen in both retina and RPE within the same regions of the blots as that seen with the patient’s antibodies. No comparable anti-45 kd immunologic activity was found in normal healthy comparison controls.
Any possible immunologic inhibition of the anti-angiogenic nature of RPDF naturally raises questions concerning the clinical significance of this abnormality. In the experience of this lab the 45 kd antigen/antibody reaction is demonstrable only in some CAR and some AMD patients, but not in normal comparison controls. Findings indicate the need to inquire further into what time might prove to be an autoimmune reaction that simultaneously encourages cancers to proliferate through the provision of a nurturing blood supply in some CAR patients, and retinas to degenerate due to a loss of control over excessive pathologic vascular proliferations in some AMD patients.
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