Autoantibodies in Endometriosis Sera Recognize a Thomsen–Friedenreich-like Carbohydrate Antigen

Lang, Gillian A.; Yeaman, Grant R.

doi:10.1006/jaut.2000.0465

Cited by 41 publications

(24 citation statements)

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“…Although the biologic functions of carbohydrate moieties are not yet fully understood, N-glycans of laminin were shown to be important for cell adhesion and spreading as well as for neurite outgrowth formation (Dennis et al, 1984;Dean et al, 1990) while unglycosylated type VII collagen could not be secreted by cultured cells into the medium (Chen et al, 1997). In addition, carbohydrate antigenic determinants were demonstrated to be important for autoantibody response in several diseases, including pernicious anemia, chronic Chagas' disease, rheumatoid arthritis, and endometriosis (Goldkorn et al, 1989;Almeida et al, 1994;Blass et al, 1998;Lang and Yeaman, 2001). Removal of asparagine-linked oligosaccharides from p200 did not a¡ect antigen recognition by patients' autoantibodies, indicating that its epitopes are glycosylation-independent.…”

Section: Discussionmentioning

confidence: 96%

The Autoantigen of Anti-p200 Pemphigoid Is an Acidic Noncollagenous N-Linked Glycoprotein of the Cutaneous Basement Membrane

Shimanovich

Hirako

Sitaru

et al. 2003

Journal of Investigative Dermatology

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Anti-p200 pemphigoid is an autoimmune subepidermal blistering disease characterized by autoantibodies to a 200-kDa protein (p200) of the dermal-epidermal junction (DEJ). p200 has been demonstrated to be distinct from all major DEJ autoantigens and is thought to be important for cell-matrix adhesion. This study provides the first biochemical characterization of p200. Differential extraction experiments demonstrated that efficient recovery of p200 from the dermis was strongly dependent on the presence of reducing agents, suggesting that it forms highly insoluble oligomers and/or is extensively cross-linked to other extracellular matrix components by disulfide bonding. p200 was resistant to digestion with bacterial collagenase, whereas this treatment did degrade major collagenous proteins of the dermis, including type I, VI, and VII collagen. This finding firmly established the noncollagenous nature of p200. N-Glycosidase F reduced the molecular size of the p200 autoantigen from 200 to 190 kDa without decreasing its immunoreactivity. In contrast, digestion of p200 with neuraminidase, O-glycosidase, chondroitinase ABC, and heparitinase I had no effect on its electrophoretic mobility. These data suggest that the p200 molecule contains N-glycans but lacks O-linked oligosaccharides and chondroitin/heparan sulfate side chains. Two-dimensional gel electrophoresis demonstrated that p200 is an acidic protein with an isoelectric point of 5.4 to 5.6. Six different p200-specific sera recognized an identical protein spot of two-dimensionally separated dermal extracts, confirming that patients with this novel autoimmune disease indeed form a single pathobiochemical entity.

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Section: Discussionmentioning

confidence: 96%

The Autoantigen of Anti-p200 Pemphigoid Is an Acidic Noncollagenous N-Linked Glycoprotein of the Cutaneous Basement Membrane

Shimanovich

Hirako

Sitaru

et al. 2003

Journal of Investigative Dermatology

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“…However, these protein microarrays employed recombinant proteins that may not have the same posttranslational modifications and native configurations recognized by the autoantibodies. It has been reported that removal of the carbohydrate moieties of Thomsen-Friedenreich antigen caused the loss of binding of autoantibodies (37, 38). Therefore, strategies that employ native antigens derived from diseased materials may add significant value to identify the authentic autoantibody-antigen reactivities.…”

Section: Discussionmentioning

confidence: 99%

Autoantibody profiling to identify biomarkers of key pathogenic pathways in mucinous ovarian cancer

Tang

Yang

et al. 2010

European Journal of Cancer

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Mucinous epithelial ovarian cancers are clinically and morphologically distinct from the other histopathologic subtypes of ovarian cancer. Unlike other ovarian subtypes, epidemiologic studies have indicated that tobacco exposure is a significant risk factor for developing mucinous ovarian cancer. Detection of autoantibody reactivity is useful in biomarker discovery and for explaining the role of important pathophysiologic pathways in disease. In order to study if there are specific antibody biomarkers in the plasma samples of mucinous ovarian cancer patients, we have initiated a screen by employing a "reverse capture antibody microarray" platform that uses native host antigens derived from mucinous ovarian tissues as "baits" for the capture of differentially labeled patient and control autoantibodies. 35 autoantibodies that were significantly elevated in the cancer plasma samples compared with healthy controls, and six autoantibodies that segregated smoking and nonsmoking patients were identified. Functional annotation of the antibody targets has identified nine target antigens involved in integrin and Wnt signaling pathways. Immunohistochemistry of archived ovarian specimens showed significant overexpression of eight of the nine target antigens in mucinous ovarian tumor tissues, suggesting that plasma autoantibodies from mucinous ovarian cancer patients might have heightened reactivities with epitopes presented by these overexpressed antigens. Autoantibody profiling may have an unexpected utility in uncovering key signaling pathways that are dysregulated in the system of interest.

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“…Le marqueur le plus prometteur est constitué par les anticorps contre les protéines porteuses de l'antigène de Thomsen-Friedenreich [26]. Une étude préliminaire, portant sur 100 patientes ayant une endométriose prouvée par coelioscopie comparées à 100 femmes sans endométriose, a montré que le dosage de ce marqueur avait une sensibilité de 75 à 80 % et une spécificité de 80 à 84 % [27].…”

Section: Promesses De La Recherche Concernant Les Marqueurs Plasmatiquesunclassified

Le coaching de l'endométriose

Audebert¹

2006

Gynécologie Obstétrique & Fertilité

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Autoantibodies in Endometriosis Sera Recognize a Thomsen–Friedenreich-like Carbohydrate Antigen

Cited by 41 publications

References 64 publications

The Autoantigen of Anti-p200 Pemphigoid Is an Acidic Noncollagenous N-Linked Glycoprotein of the Cutaneous Basement Membrane

The Autoantigen of Anti-p200 Pemphigoid Is an Acidic Noncollagenous N-Linked Glycoprotein of the Cutaneous Basement Membrane

Autoantibody profiling to identify biomarkers of key pathogenic pathways in mucinous ovarian cancer

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