2012
DOI: 10.4049/jimmunol.1102132
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Abstract: Self-reactive natural antibodies initiate injury following ischemia and reperfusion of certain tissues, but their role in ischemic stroke is unknown. We investigated neoepitope expression in the post-ischemic brain, and the role of natural antibodies in recognizing these epitopes and mediating complement-dependent injury. A novel IgM mAb recognizing a subset of phospholipids (C2) and a previously characterized anti-annexin IV mAb (B4) were used to reconstitute and characterize injury in antibody deficient Rag1… Show more

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Cited by 61 publications
(111 citation statements)
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References 48 publications
(100 reference statements)
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“…So-called natural IgM Abs are produced mainly by the B-1 subset of B lymphocytes, and the screening of hybridomas generated from an enriched B-1 cell fraction led to the identification of an IgM mAb that recognized non-muscle myosin expressed in reperfused tissues 2, 3 . Our recent studies have identified additional targets for self-reactive natural Abs on post-ischemic tissue, namely annexin IV and a subset of phospholipids that are expressed in the post-ischemic intestine and brain 4, 5 . Thus, the above studies suggest that ischemia-induced neoepitopes or corresponding self-reactive natural Abs represent targets for therapeutic intervention of ischemia reperfusion injury (IRI).…”
Section: Introductionmentioning
confidence: 99%
“…So-called natural IgM Abs are produced mainly by the B-1 subset of B lymphocytes, and the screening of hybridomas generated from an enriched B-1 cell fraction led to the identification of an IgM mAb that recognized non-muscle myosin expressed in reperfused tissues 2, 3 . Our recent studies have identified additional targets for self-reactive natural Abs on post-ischemic tissue, namely annexin IV and a subset of phospholipids that are expressed in the post-ischemic intestine and brain 4, 5 . Thus, the above studies suggest that ischemia-induced neoepitopes or corresponding self-reactive natural Abs represent targets for therapeutic intervention of ischemia reperfusion injury (IRI).…”
Section: Introductionmentioning
confidence: 99%
“…The Infarct size coefficient of variation (in the total 500 control groups9101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107108109110…”
Section: Resultsmentioning
confidence: 99%
“…Using high doses of purified single IgM mAb in RAG−/− mice, the anti-ANX4 mAb B4 led to IR injury in the otherwise protected RAG−/− mice [50, 56]. Finally, this same pathogenic NatAb system also appears to be present in humans, based on the: 1) Presence of human serum NatAbs that recognize recombinant ANX4 [50]; 2) Cross-reactivity of mAb B4 with neoepitopes elaborated on oxidatively stressed human endothelial cells [57] and human retinal pigmented epithelial cells [51] (Rohrer, unpublished observations); and 3) Expression of the neoepitope recognized by the B4 NatAb in injured human tissues (unpublished observations).…”
Section: Natural Antibody-mediated Tissue Injurymentioning
confidence: 99%