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https://www.readbyqxmd.com/read/29333938/structure-based-engineering-to-restore-high-affinity-binding-of-an-isoform-selective-anti-tgf%C3%AE-1-antibody
#1
Dana M Lord, Julie J Bird, Denise M Honey, Annie Best, Anna Park, Ronnie R Wei, Huawei Qiu
Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFβ1-specific antagonist. It was tested in clinical trials for the treatment of scleroderma but later terminated due to lack of efficacy. Subsequent characterization of CAT192 indicated that its TGFβ1 binding affinity was reduced by ∼50-fold upon conversion from the parental single-chain variable fragment (scFv) to IgG4. We hypothesized this result was due to decreased conformational flexibility of the IgG that could be altered via engineering...
January 15, 2018: MAbs
https://www.readbyqxmd.com/read/29333745/increased-sensitivity-and-high-specificity-of-indirect-immunofluorescence-in-detecting-igg-subclasses-for-diagnosis-of-bullous-pemphigoid
#2
J Jankásková, O N Horváth, R Varga, P Arenberger, E Schmidt, T Ruzicka, M Sárdy
BACKGROUND: Indirect immunofluorescence (IIF) microscopy on monkey oesophagus is an important assay for the diagnosis of bullous pemphigoid (BP). Its relatively low sensitivity (60-80%) may be partly due to insufficient detection of minor IgG subclasses. AIM: To determine the operating characteristics of an IgG subclass in IIF. METHODS: We designed a retrospective, dual-centre, controlled cohort study on sera from 64 BP sera that had been rated as false negatives by traditional IIF microscopy, and assessed circulating IgG1 , IgG3 and IgG4 autoantibodies...
January 14, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29332510/localized-autoimmune-pancreatitis-mimicking-pancreatic-cancer-case-report-and-literature-review
#3
Wen-Ling Hsu, Shu-Min Chang, Pei-Yin Wu, Chin-Chuan Chang
Autoimmune pancreatitis (AP) is a rare autoimmune pancreatic manifestation of systemic immunoglobulin G4 (IgG4)-related sclerosing disease. Distinguishing between AP and pancreatic cancer is crucial because the clinical courses, treatments, and prognoses of these two disease entities are quite different. We herein report a case involving a 52-year-old man with subacute epigastralgia who visited our hospital for evaluation of a suspicious pancreatic mass found during esophagogastroduodenoscopy. Enhanced computed tomography (CT) revealed an enlarged lesion in the pancreatic head with encasement of hepatic vessels...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29332094/low-dose-oral-immunotherapy-using-low-egg-allergen-cookies-for-severe-egg-allergic-children-reduces-allergy-severity-and-affects-allergen-specific-antibodies-in-serum
#4
Akihiro Maeta, Marin Matsushima, Nozomi Muraki, Mariko Asano, Yuri Takaoka, Makoto Kameda, Kyoko Takahashi
BACKGROUND: We evaluated the safety and efficacy of low-egg-allergen cookies (LAC) as low-dose oral immunotherapy (OIT) in children with severe egg allergy. We also examined the relationship between mild desensitization by low-dose OIT and serum biomarkers of allergy. METHODS: We enrolled 13 children with egg allergy who could not receive OIT with hard-boiled egg white (EW). For 11 participants, OIT was carried out using LAC for 3-4 months. Open food challenges with hard-boiled EW and blood samplings were performed before and after OIT...
January 13, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29329570/exophthalmos-in-a-young-woman-with-no-graves-disease-a-case-report-of-igg4-related-orbitopathy
#5
Annamaria Erdei, Zita Steiber, Csaba Molnar, Ervin Berenyi, Endre V Nagy
BACKGROUND: Immunoglobulin G4-related disease (IgG4-rd) is characterized by lymphoplasmacytic infiltration and tissue fibrosis. Orbital manifestations of IgG4-rd may include unilateral or bilateral proptosis, cicatricial extraocular muscle myopathy, orbital inflammation and pain which may mimic ophthalmic Graves' disease. CASE PRESENTATION: A 25-year-old woman has been referred to the endocrinology clinic, 4 months after delivery, with suspected Graves' orbitopathy...
January 12, 2018: BMC Ophthalmology
https://www.readbyqxmd.com/read/29324858/mapping-the-geographical-distribution-of-podoconiosis-in-cameroon-using-parasitological-serological-and-clinical-evidence-to-exclude-other-causes-of-lymphedema
#6
Kebede Deribe, Amuam Andrew Beng, Jorge Cano, Abdel Jelil Njouendo, Jerome Fru-Cho, Abong Raphael Awah, Mathias Esum Eyong, Patrick W Chounna Ndongmo, Emanuele Giorgi, David M Pigott, Nick Golding, Rachel L Pullan, Abdisalan M Noor, Fikre Enquselassie, Christopher J L Murray, Simon J Brooker, Simon I Hay, Peter Enyong, Melanie J Newport, Samuel Wanji, Gail Davey
BACKGROUND: Podoconiosis is a non-filarial elephantiasis, which causes massive swelling of the lower legs. It was identified as a neglected tropical disease by WHO in 2011. Understanding of the geographical distribution of the disease is incomplete. As part of a global mapping of podoconiosis, this study was conducted in Cameroon to map the distribution of the disease. This mapping work will help to generate data on the geographical distribution of podoconiosis in Cameroon and contribute to the global atlas of podoconiosis...
January 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29324739/mansonella-perstans-microfilaremic-individuals-are-characterized-by-enhanced-type-2-helper-t-and-regulatory-t-and-b-cell-subsets-and-dampened-systemic-innate-and-adaptive-immune-responses
#7
Manuel Ritter, Winston Patrick Chounna Ndongmo, Abdel Jelil Njouendou, Nora Nganyewo Nghochuzie, Lucy Cho Nchang, Dizzle Bita Tayong, Kathrin Arndts, Norman Nausch, Marc Jacobsen, Samuel Wanji, Laura E Layland, Achim Hoerauf
The filarial nematode Mansonella perstans is endemic throughout Africa, northern South America and the Caribbean. Interestingly, M. perstans-infected individuals present no distinct clinical picture associated with certain pathology. Due to its relatively silent nature, research on this tropical disease has been neglected, especially M. perstans-driven immune responses. A hindrance in obtaining data on M. perstans-specific responses has been the inability to obtain adult worms since their habitats in serous cavities are difficult to access...
January 11, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29323079/immunoglobulin-g4-related-tubulointerstitial-nephritis-a-not-to-be-missed-diagnosis
#8
Smita Mary Matthai, Anjali Mohapatra, Raiyani Palak, Gopal Basu
Immunoglobulin G4-related tubulointerstitial nephritis (IgG4-TIN) is a newly recognized clinicopathological entity characterized by a dense interstitial infiltrate of IgG4-positive plasma cells accompanied by fibrosis and obliterative phlebitis causing acute or chronic renal dysfunction amenable to corticosteroid therapy. IgG4-TIN is the dominant manifestation of renal involvement in IgG4-related disease (IgG4-RD) which is a novel, immune-mediated, fibroinflammatory and multiorgan disorder. We describe a case of IgG4-TIN with isolated renal involvement in an elderly male patient with poor response to corticosteroid therapy...
October 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29322510/lolium-perenne-peptide-immunotherapy-is-well-tolerated-and-elicits-a-protective-b-cell-response-in-seasonal-allergic-rhinitis-patients
#9
R Mösges, A F Koch, E Raskopf, J Singh, K Shah-Hosseini, B Hauswald, Y Yarin, F Corazza, L Haazen, S Pirotton, S Allekotte, G Zadoyan, T Legon, S R Durham, M H Shamji
BACKGROUND: Systemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short-course treatment with adjuvant-free Lolium perenne peptides (LPP) following a 6-week dose-escalation protocol. METHODS: In a prospective, dose-escalation study, 61 grass pollen-allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events...
January 10, 2018: Allergy
https://www.readbyqxmd.com/read/29319188/immunoprofile-of-%C3%AE-gal-and-b-antigen-specific-responses-differentiate-red-meat-allergic-patients-from-healthy-individuals
#10
Danijela Apostolovic, Rui Da Silva Rodrigues, Preethi Thomas, Maria Starkhammar, Carl Hamsten, Marianne van Hage
BACKGROUND: The Galactose-α-1,3-galactose (α-Gal) epitope is involved in red meat allergy. As α-Gal is structurally similar to the blood group B antigen, we explored the relationship between the immune responses to α-Gal- and the B-antigen in red meat allergic patients compared to healthy A/O or B blood donors. METHODS: Sera from 51 red meat allergic patients IgE positive to α-Gal and 102 healthy blood donors (51 blood group A/O; 51 blood group B), were included...
January 10, 2018: Allergy
https://www.readbyqxmd.com/read/29315494/isotype-dependent-on-column-non-reversible-aggregation-of-monoclonal-antibodies
#11
Monika Farys, Daniel Gibson, Alan Lewis, Will Lewis, Richard Kucia-Tran
Monoclonal antibodies of the IgG2 and IgG4 isotype were found to exhibit an increased propensity for displaying two-peak elution profiles during cation exchange chromatography. In some cases, this two-peak elution profile also resulted in the formation of non-reversible mAb aggregates. Comparison of IgG1, IgG2 and IgG4 molecules with the same variable region reveals that the two-peak behaviour is predominantly mediated by the constant region and most likely the lower CH1, hinge and upper CH2 regions of the mAb...
January 8, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29313477/evaluation-of-the-diagnostic-performance-of-onchocerca-volvulus-linear-epitopes-in-a-peptide-enzyme-linked-immunosorbent-assay
#12
Ole Lagatie, Ann Verheyen, Erik Nijs, Bieke Van Dorst, Linda Batsa Debrah, Alex Debrah, Taniawati Supali, Erliyani Sartono, Lieven J Stuyver
Diagnostic tools for the detection of infection with Onchocerca volvulus are presently limited to microfilaria detection in skin biopsies and serological assessment using the Ov16 immunoglobulin G4 (IgG4) rapid test, both of which have limited sensitivity. We have investigated the diagnostic performance of a peptide enzyme-linked immunosorbent assay (ELISA) based on immunodominant linear epitopes previously discovered. Peptides that were used in these assays were designated O. volvulus motif peptides (OvMP): OvMP-1 (VSV-EPVTTQET-VSV), OvMP-2 (VSV-KDGEDK-VSV), OvMP-3 (VSV-QTSNLD-VSV), and the combination of the latter two, OvMP-23 (VSV-KDGEDK-VSV-QTSNLD-VSV)...
January 8, 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29313446/monoclonal-antibody-higher-order-structure-analysis-by-high-throughput-protein-conformational-array
#13
Yuanli Song, Deqiang Yu, Mukesh Mayani, Nesredin Mussa, Zheng Jian Li
The elucidation of antibody higher order structure (HOS) is critical in therapeutic antibody development. Since HOS determines the protein bioactivity and chemo-physical properties, this knowledge can help to ensure that the safety and efficacy attributes are not compromised. Protein conformational array (PCA) is a novel method for determining the HOS of monoclonal antibodies. Previously, we successfully utilized an enzyme-linked immunosorbent assay (ELISA)-based PCA along with other bioanalytical tools to elucidate the structures of antibody aggregates...
January 9, 2018: MAbs
https://www.readbyqxmd.com/read/29313399/localized-intrahepatic-igg4-related-sclerosing-cholangitis-igg4-sc-as-an-additional-type-of-igg4-sc-a-systematic-analysis-of-12-cases
#14
Zhichao Mo, Kuvaneshan Ramen, Yunfeng Shan, Mengtao Zhou, Xiangwu Zheng, Xiuling Wu, Zhengping Yu, Xiaoke Ji, Qiyu Zhang, Qiqiang Zeng
OBJECTIVES: IgG4-related sclerosing cholangitis (IgG4-SC), a recently defined disease entity, has been classified into four types based on the stricture regions revealed by cholangiography. However, localized intrahepatic IgG4-SC is not included into the classification. This study aimed to analyze and characterize localized intrahepatic IgG4-SC and justify the inclusion of this type into the classification. METHODS: PubMed and Embase were searched for studies published from March 2001 to June 2017 reporting localized intrahepatic IgG4-SC...
January 9, 2018: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/29313220/pemphigus-a-comprehensive-review-on-pathogenesis-clinical-presentation-and-novel-therapeutic-approaches
#15
REVIEW
Robert Pollmann, Thomas Schmidt, Rüdiger Eming, Michael Hertl
Pemphigus is a group of rare, potentially devastating autoimmune diseases of the skin and mucous membranes with high morbidity and potentially lethal outcome. The major clinical variant, pemphigus vulgaris (PV) is caused by a loss of intercellular adhesion of epidermal keratinocytes which is induced by IgG autoantibodies against components of desmosomes. Specifically, IgG against the desmosomal adhesion proteins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1), preferentially target their ectodomains which are presumably critical for the transinteraction and signalling function of these adhesion molecules...
January 8, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29311390/hepatitis-b-virus-reactivation-during-steroid-treatment-of-igg4-related-disease
#16
Alexandra Shingina, Robert Puckrin, Aliya Gulamhusein
No abstract text is available yet for this article.
December 27, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/29310344/polymyositis-with-elevated-serum-igg4-levels-and-abundant-igg4-plasma-cell-infiltration-a-case-report-and-literature-review
#17
Ryusuke Anan, Mitsuhiro Akiyama, Yuko Kaneko, Jun Kikuchi, Kazuko Suzuki, Shiro Matsubara, Tsutomu Takeuchi
INTRODUCTION: Polymyositis (PM) is a type of autoimmune, inflammatory myopathy. IgG4-related disease (IgG4-RD) is a recently recognized disease entity characterized by elevated serum IgG4 levels and IgG4 plasma-cell infiltration of various organs. However, several reports have described cases of other diseases that present with those features, suggesting the importance of careful differential diagnosis. Herein, we report the first case of PM with elevated serum IgG4 levels and IgG4 plasma cells in the muscles, mimicking IgG4-RD...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29307589/pathogenic-igg4-autoantibodies-from-endemic-pemphigus-foliaceus-recognize-a-desmoglein-1-conformational-epitope
#18
Flor Evangelista, Aleeza J Roth, Phillip Prisayanh, Brenda R Temple, Ning Li, Ye Qian, Donna A Culton, Zhi Liu, Oliver J Harrison, Julia Brasch, Barry Honig, Lawrence Shapiro, Luis A Diaz
Fogo Selvagem (FS), the endemic form of pemphigus foliaceus, is mediated by pathogenic IgG4 autoantibodies against the amino-terminal extracellular cadherin domain of the desmosomal cadherin desmoglein 1 (Dsg1). Here we define the detailed epitopes of these pathogenic antibodies. Proteolytic footprinting showed that IgG4 from 95% of FS donor sera (19/20) recognized a 16-residue peptide (A129LNSMGQDLERPLELR144) from the EC1 domain of Dsg1 that overlaps the binding site for an adhesive-partner desmosomal cadherin molecule...
January 4, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29298790/a-case-of-igg4oligoarthritis-mimicking-psoriatic-arthritis
#19
Ziad Farah, Neil Mo
IgG4-related disease (IgG4-RD) is a rare but rapidly emerging immune-mediated fibroinflammatory condition that can affect almost any organ. It is typically associated with involvement of organs such as lymph nodes, submandibular glands, orbits, periaortic region and pancreas. However, IgG4-RD presenting primarily as an inflammatory arthritis is much less recognised. We present a rare case of IgG4-RD mimicking psoriatic arthritis. In spite of normal circulating IgG4 plasma levels, a clinical index of suspicion was required to obtain a histopathological diagnosis...
January 3, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29297990/video-assisted-thoracoscopic-surgery-can-help-enable-the-complete-resection-of-a-mediastinal-tumor-caused-by-immunoglobulin-g4-related-disease-and-avoid-the-need-for-postoperative-medication-a-case-report
#20
Tsuyoshi Uchida, Hirochika Matsubara, Satoshi Nagasaka, Satsuki Kina, Tomofumi Ichihara, Hiroyasu Matsuoka, Hiroyuki Nakajima
Immunoglobulin (Ig) G4-related disease has various clinical signs and symptoms, and steroidal therapy with corticosteroids has been found to be effective for treatment. Few cases of IgG4-related disease associated with paravertebral tumor have been reported, and there have been no reports on complete resection of such a tumor. Here, we report a case of IgG4-related disease associated with a paravertebral tumor that was successfully resected without the need for postoperative medication. An 84-year-old woman was admitted to our hospital with a paravertebral tumor...
January 3, 2018: Asian Journal of Endoscopic Surgery
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