Pathogenic Natural Antibodies Recognizing Annexin IV Are Required to Develop Intestinal Ischemia-Reperfusion Injury
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PROVIDER: PRJNA112027 | ENA |
REPOSITORIES: ENA
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Project description:Intestinal ischemia-reperfusion (IR) injury is initiated when natural IgM antibodies recognize neo-epitopes that are revealed on ischemic cells. The target molecules and mechanisms whereby these neo-epitopes become accessible to recognition are not well understood. Proposing that isolated intestinal epithelial cells (IEC) may carry IR-related neo-epitopes, we used in vitro IEC binding assays to screen hybridomas created from B cells of unmanipulated wild type C57BL/6 mice. We identified a novel IgM monoclonal antibody (mAb B4) that reacted with the surface of IEC by flow cytometric analysis and was alone capable of causing complement activation, neutrophil recruitment and intestinal injury in otherwise IR-resistant Rag1-/- mice. Monoclonal Ab B4 was found to specifically recognize mouse annexin IV. Pre-injection of recombinant annexin IV blocked IR injury in wild type C57BL/6 mice, demonstrating the requirement for recognition of this protein in order to develop IR injury in the context of a complex natural antibody repertoire. Humans were also found to exhibit IgM natural antibodies that recognize annexin IV. These data in toto identify annexin IV as a key ischemia-related target antigen that is recognized by natural Abs in a pathologic process required in vivo to develop intestinal IR injury. Keywords: Natural antibodies, Annexin, Ischemia Reperfusion, Inflammation, Complement
2009-02-19 | GSE14862 | GEO
Project description:Intestinal ischemia-reperfusion (IR) injury is initiated when natural IgM antibodies recognize neo-epitopes that are revealed on ischemic cells. The target molecules and mechanisms whereby these neo-epitopes become accessible to recognition are not well understood. Proposing that isolated intestinal epithelial cells (IEC) may carry IR-related neo-epitopes, we used in vitro IEC binding assays to screen hybridomas created from B cells of unmanipulated wild type C57BL/6 mice. We identified a novel IgM monoclonal antibody (mAb B4) that reacted with the surface of IEC by flow cytometric analysis and was alone capable of causing complement activation, neutrophil recruitment and intestinal injury in otherwise IR-resistant Rag1-/- mice. Monoclonal Ab B4 was found to specifically recognize mouse annexin IV. Pre-injection of recombinant annexin IV blocked IR injury in wild type C57BL/6 mice, demonstrating the requirement for recognition of this protein in order to develop IR injury in the context of a complex natural antibody repertoire. Humans were also found to exhibit IgM natural antibodies that recognize annexin IV. These data in toto identify annexin IV as a key ischemia-related target antigen that is recognized by natural Abs in a pathologic process required in vivo to develop intestinal IR injury. Keywords: Natural antibodies, Annexin, Ischemia Reperfusion, Inflammation, Complement In the study presented here, a total of 4 custom spotted antigen slides were hybridized with known antibodies.
2010-05-05 | E-GEOD-14862 | biostudies-arrayexpress
Project description:Purpose: This study uses a high-throughput glycan microarray to evaluate the immunological evolution of antibodies to the glyco-antigen GD2. The goal is to determine germline and affinity mature antibody specificity and affinities/ Results: Affinity mature anti-GD2 antibodies 3F8 and ch14.18 had high affinity and were highly specific for the target GD2. Germline antibodies were also hihgly specific and had surprisingly high affinity. Conclusion: Antibodies to GD2 evolved from highly specific germlines. Highly specific germlines may be critical in evading autoimmunity issues.
2017-08-25 | GSE100307 | GEO
Project description:Annexin family is the largest category of eukaryotic calcium and phospholipid-binding proteins and plays important roles in various physiological processes, including cell differentiation and proliferation. More than 160 Annexin proteins are classified into 65 different speciesAs a new member of Annexin family, the role of ANXA10 in cancer progression is rarely investigated, and its expression and function in CCA need more experiments to reveal.
2022-05-17 | GSE132279 | GEO
Project description:Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies IV
| PRJNA391736 | ENA
Project description:Repair of injured muscle involves repair of injured myofibers through the involvement of dysferlin and its interacting partners, including annexin. Studies with mice and patients have established that dysferlin deficit leads to chronic inflammation and adipogenic replacement of the diseased muscle. However, longitudinal analysis of annexin deficit on muscle pathology and function is lacking. Here we show that unlike annexin A1, but similar to dysferlin, lack of annexin A2 (AnxA2) causes poor myofiber repair and progressive weakening with age. However, unlike dysferlin-deficient muscle, AnxA2-deficient muscles do not exhibit chronic inflammation or adipogenic replacement. Deletion of AnxA2 in dysferlin deficient mice reduces inflammation, adipogenic replacement, and loss in muscle function caused by dysferlin deficit. These results show that: a) AnxA2 facilitates myofiber repair, b) chronic inflammation and adipogenic replacement of dysferlinopathic muscle requires AnxA2, and c) inhibiting AnxA2-mediated inflammation is a novel therapeutic avenue for dysferlinopathy.
2016-10-04 | GSE87557 | GEO
Project description:The glucocorticoid-inducible protein annexin A1 has been shown to function as key-regulator of the resolution phase of inflammation but its role in immune-mediated crescentic glomerulonephritis has not been studied so far. Acute crescentic glomerulonephritis was induced in annexin A1 deficient and wildtype mice using a sheep serum against rat glomerular basement membrane constituents. Alterations in gene expression were determined by RNA-Seq and gene ontology analysis. Intrinsic annexin A1 has a protective effect in reducing pro-inflammatory signals and infiltration of neutrophil granulocytes during crescentic GN. The annexin A1 signaling cascade may therefore provide novel targets for the treatment of inflammatory kidney disease.
2022-10-04 | GSE204873 | GEO
Project description:Infection and vaccination repeatedly expose individuals to antigens that are conserved between influenza virus subtypes. Nevertheless, antibodies recognizing conserved influenza epitopes greatly outnumber antibodies reactive against variable epitopes. Elucidating factors contributing to the paucity of broadly reactive influenza antibodies remains a major obstacle for developing a universal influenza vaccine. Here, we report that inducing broadly reactive influenza antibodies increases autoreactive antibodies in humans and mice and exacerbates disease in four distinct models of autoimmune disease. Importantly, transferring broadly reactive influenza antibodies augments disease in the presence of inflammation or autoimmune susceptibility. Further, broadly reactive influenza antibodies spontaneously arise in mice with defects in B cell tolerance. Together, these data suggest that self-tolerance mechanisms limit the prevalence of broadly reactive influenza antibodies, which can exacerbate disease in the context of additional risk factors.
2022-02-09 | GSE196366 | GEO
Project description: Not available
| S-EPMC5578160 | biostudies-literature
Project description: Not available
| S-EPMC10880127 | biostudies-literature