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Discover how PEPperPRINT Peptide Microarray products have been used in different fields of research.

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Anti-COX-2 Autoantibody is a Novel Marker of Immune Aplastic Anemia

Kelkka, Tiina; Tyster, Mikko; Lundgren, Sofie; Feng, Xingmin; Kerr, Cassandra; Hosokawa, Kohei; Huuhtanen, Jani; Keränen, Mikko; Kawakami, Toru; Patel, Bhavisha; Maeda, Yuka; Nieminen, Otso; Kasanen, Tiina; Aronen, Pasi; Yadav, Bhagwan; Rajala, Hanna; Nakazawa, Hideyuki; Jaatinen, Taina; Hellstrom-Lindberg, Eva; Ogawa, Seishi; Ishida, Fumihiro; Nishikawa, Hiroyoshi; Nakao, Shinji; Maciejewski, Jaroslaw; Young, Neal S.; Mustjoki, Satu
May 2022
10.21203/rs.3.rs-1653776/v1
In immune aplastic anemia (IAA), severe pancytopenia results from the immune-mediated destruction of hematopoietic stem cells. Several autoantibodies have been reported, but no clinically applicable autoantibody tests are available for IAA. We screened autoantibodies using a microarray containing > 9 000 proteins and validated the findings in a large international cohort of IAA patients (n = 405) and controls (n = 815). We identified a novel autoantibody that binds to the C-terminal end of cyclo-oxygenase 2 (COX-2, aCOX-2 Ab). 37% of all adult IAA patients tested positive for aCOX-2 Ab, while only 1.7% of the controls were aCOX-2 Ab positive. Sporadic non-IAA aCOX-2 Ab positive cases were observed among patients with related bone marrow failure diseases, multiple sclerosis, and type I diabetes, whereas no aCOX-2 Ab seropositivity was detected in the healthy controls, in patients with non-autoinflammatory diseases or rheumatoid arthritis. In IAA, anti-COX-2 Ab positivity correlated with age and the HLA-DRB1*15:01 genotype. 83% of the > 40 years old IAA patients with HLA-DRB1*15:01 were anti-COX-2 Ab positive, indicating an excellent sensitivity in this group. aCOX-2 Ab positive IAA patients also presented lower platelet counts. Our results suggest that aCOX-2 Ab defines a distinct subgroup of IAA and may serve as a valuable diagnostic tool.

Heterotypic Assembly Mechanism Regulates CHIP E3 Ligase Activity

Das, Aniruddha; Thapa, Pankaj; Santiago, Ulises; Shanmugam, Nilesh; Banasiak, Katarzyna; Dabrowska, Katarzyna; Nolte, Hendrik; Szulc, Natalia A.; Gathungu, Rose M.; Cysewski, Dominik; Krüger, Marcus; Dadlez, Michal; Nowotny, Marcin; Camacho, Carlos J.; Hoppe, Thorsten; Pokrzywa, Wojciech
Aug 2021
10.1101/2021.08.20.457118
The E3 ubiquitin ligases CHIP/CHN-1 and UFD-2 team up to accelerate ubiquitin chain formation. However, it remained largely unclear how the high processivity of this E3 set is achieved. Here we studied the molecular mechanism and function of the CHN-1/UFD-2 complex in Caenorhabditis elegans. Our data show that UFD-2 binding promotes the cooperation between CHN-1 and ubiquitin-conjugating E2 enzymes by stabilizing the CHN-1 U-box dimer. The HSP-1 chaperone outcompetes UFD-2 for CHN-1 binding and promotes the auto-inhibited CHN-1 state by acting on the conserved position of the U-box domain. The interaction with UFD-2 enables CHN-1 to efficiently ubiquitinate S-Adenosylhomocysteinase (AHCY-1), an enzyme crucial for lipid metabolism. Our results define the molecular mechanism underlying the synergistic cooperation of CHN-1 and UFD-2 in substrate ubiquitylation.

FUSION PROTEIN CONSTRUCTSCOMPRISING ANTI-C3d ANTIBODY AND FACTOR H

Curtis, Michael Steven; Storek, Michael; Violette, Shelia Marie; Kalled, Susan L.; Fahnoe, Kelly C.; Huang, Cheng Ran; Stark, Ellen Garber; Taylor, Frederick Robbins; Caravella, Justin Andrew; Holers, Vernon Michael; Gambel, Phillip
Jan 2021
Provided herein are fusion protein constructs that can bind a complement-associated antigen, comprising a targeting moiety and a complement modulator protein, or a fragment thereof or a variant thereof. The targeting moiety is an antibody or an antigen binding fragment thereof, in some examples. Further provided are methods of using the fusion protein constructs, for example, in treating complement mediation conditions.

Marker Sequences for Diagnosing and Stratifying Systemic Sclerosis Patients

Budde, Petra
Jan 2021
The present invention relates to methods for identifying markers for systemic sclerosis (also scleroderma; SSc) and to the markers identified with the aid of this method, which can differentiate between SSc and other autoimmune diseases on the one hand and between different SSc subgroups on the other hand. The invention also relates to panels, diagnostic devices and test kits which comprise these markers, and to the use and application thereof, for example for the diagnosis, prognosis and therapy control of SSc. The invention also relates to methods for screening and for validating active substances for use in SSc.

Compounds and Methods Targeting Interleukin-19

Higgs Jr., Richard Earl; Konrad, Robert John; Nickoloff, Brian Jeffrey; Siegel II, Robert William; Mertz, Prema Maria
Nov 2020
The present invention provides compounds and methods targeting human interleukin-19, including therapeutic antibodies, pharmaceutical compositions and diagnostic applications useful in the field of immune-mediated diseases including psoriasis, atopic dermatitis, psoriatic arthritis, bronchial asthma and diabetic nephropathy.

Monoclonal Antibodies to Growth and Differentiation Factor 15 (gdf-15), and Uses Thereof for Treating Cancer Cachexia and Cancer

Wischhusen, Jörg; Junker, Markus; Schäfer, Tina; Pühringer, Dirk; Lucas, Zachariah
Oct 2020
The present invention relates to monoclonal anti-human-GDF-15 antibodies. The antibodies include chimeric anti-bodies and humanized antibodies. The invention also relates to monoclonal anti-human-GDF-15 antibodies including murine anti-bodies, chimeric antibodies and humanized antibodies for use in methods for the treatment of cancer cachexia and also for the treatment of cancer. The invention also provides pharmaceutical compositions, kits, methods and uses and cell lines capable of producing the monoclonal antibodies of the invention.

Novel Anti-Cd40 Antibodies and Use Thereof

Park, Chung Gyu; Kim, Jung Sik; Lucas, Zachariah
Sep 2020
The present invention relates to novel anti-CD40 antibodies and a use thereof and, more specifically, provided are a pharmaceutical composition for treating or preventing autoimmune diseases and a composition for inhibiting immune rejection during organ transplantation, both compositions containing, as an active ingredient, novel anti-CD40 antibodies that specifically bind to a novel epitope of CD40. Novel anti-CD40 antibodies of the present invention directly target CD40, but not CD40 ligands, and block the signaling of CD40-CD154 without stimulating platelets so as to exhibit excellent antagonistic effects, thereby being expected to be usable as a preparation effective in the treatment of autoimmune diseases and the inhibition of organ transplantation rejection.

IgM Fc AND J-CHAIN MUTATIONS THAT AFFECT IgM SERUM HALF-LIFE

Baliga, Ramesh; Keyt, Bruce; NG, Dean; Huynh, Phuong N.
Jul 2020
This disclosure provides an IgM antibody or IgM-like antibody comprising a variant J-chain and/or variant IgM heavy chain constant regions that can confer increased serum half-life upon the antibody.

Plasmodium Falciparum and Plasmodium Vivax Vaccine

Werner, Ekkehard
Apr 2020
The present invention relates to a vaccine V comprising (A) at least one isolated polypeptide strand P comprising or consisting of at least nine consecutive amino acid moieties of the repetitive organellar protein, putative of Plasmodium falciparum or the hypothetical protein PVNG_04523 of Plasmodium vivax or a polynucleotide strand encoding for such polypeptide; and (B) at least one pharmaceutically acceptable carrier or excipient. Furthermore, the present invention refers to an antibody binding to the repetitive organellar protein,putative of Plasmodium falciparumor the hypothetical protein PVNG_04523 of Plasmodium vivax or a polynucleotide strand encoding therefor, to a method of generating such antibody and uses thereof.

Anti-Cd95l Antibody

Gieffers, Christian; Hill, Oliver; Thiemann, Meinolf; Sykora, Jaromir; Merz, Christian; Schnyder, Tim; Fricke, Harald; Landsman, Robert S.
Apr 2020
The present invention relates to a specific CD95L antibody and to the use thereof in the treatment or diagnosis of diseases involving CD95L-induced signalling, e.g. cancer diseases.

Plasmodium Sporozoite Npdp Peptides as Vaccine and Target Novel Malaria Vaccines and Antibodies Binding To

Lanzavecchia, Antonio; Tan, Joshua Hoong Yu; Daubenberger, Claudia; Sack, Brandon
Mar 2020
The present invention provides a fragment of piasmodium circumsporozoite protein according to SEQ ID NO: 1, for example for use in a malaria vaccine. The present invention also provides nucleic acids encoding a fragment of piasmodium circumsporozoite protein according to SEQ ID NO: 1, compositions comprising a fragment of piasmodium circumsporozoite protein according to SEQ ID NO: 1 and antibodies binding to a fragment of piasmodium circumsporozoite protein according to SEQ ID NO: 1. The antibodies according to the present invention bind specifically to P. falciparum sporozoites and may be used in the treatment and/or prevention of malaria.

A canstatin-derived peptide provides insight into the role of Capillary Morphogenesis Gene 2 in angiogenic regulation and matrix uptake

Finnell, Jordan G.; Tsang, Tsz-Ming; Cryan, Lorna; Garrard, Samuel; Lee, Sai-Lun; Ackroyd, P. Christine; Rogers, Michael S.; Christensen, Kenneth A.
Jul 2019
10.1101/705459
Abstract Capillary Morphogenesis Gene 2 protein (CMG2) is a transmembrane, integrin-like receptor and the primary receptor for the anthrax toxin. In addition to its role as an anthrax toxin receptor, CMG2 has been repeatedly shown to play a role in angiogenic processes. However, the molecular mechanism mediating observed CMG2-related angiogenic effects has not been fully elucidated. Previous studies have found that CMG2 binds type IV collagen (Col-IV), a key component of the vascular basement membrane, as well as other ECM proteins. Currently, no link has been made between these CMG2-ECM interactions and angiogenesis; however, ECM fragments are known to play a role in regulating angiogenesis. Here, we further characterize the CMG2-Col-IV interaction and explore the effect of this interaction on angiogenesis. Using a peptide array, we observed that CMG2 preferentially binds peptide fragments of the NC1 (non-collagenous domain 1) domains of Col-IV. These domains are also known as the fragments arresten (from the α1 chain) and canstatin (from the α2 chain) and have documented antiangiogenic properties. A second peptide array was probed to map a putative binding epitope. A top hit from the initial array, a canstatin-derived peptide, binds to the CMG2 ligand-binding von Willebrand factor A (vWA) domain with sub-micromolar affinity (peptide S16, K d = 400 ± 200 nM). This peptide competes with anthrax protective antigen (PA) for CMG2 binding, and does not bind CMG2 in the presence of EDTA. Together these data suggest that, like PA, S16 interacts with CMG2 at the metal-ion dependent adhesion site (MIDAS) of its vWA domain. We demonstrate that CMG2 specifically mediates endocytic uptake of S16, since CMG2-/- endothelial cells show markedly reduced S16 uptake, without reducing total endocytosis. Furthermore, we show that S16 reduces endothelial migration but not cell proliferation. Taken together, our data demonstrate that a Col IV-derived anti-angiogenic peptide acts via CMG2, suggesting a possible link between CMG2-Col IV interactions and angiogenesis.

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