Birth and coming of age of islet autoantibodies

Bonifacio, Ezio; Achenbach, Peter

doi:10.1111/cei.13360

Cited by 38 publications

(35 citation statements)

References 149 publications

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“…While the clinical manifestation of AIDs varies pending the targeted organ, they all share a common etiology characterized by a collapse in the immune system that is precipitated by a complex interplay among genetic, epigenetic and environmental factors [5,6]. In particular, T1DM is defined as a T cell-mediated AID caused by the breakdown in the balance between T regulatory cells (Tregs) and T effector cells (Teffs) that respond to islet-associated self-antigens such as insulin, glutamic acid decarboxylase 65 (GAD65), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8) being the predominant ones [7]. This collapse in immune homeostasis or 'tolerance' leads to beta-cell destruction and hyperglycemia [8,9].…”

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confidence: 99%

Time for a paradigm shift in treating type 1 diabetes mellitus: coupling inflammation to islet regeneration

Cobo-Vuilleumier

Gauthier

2020

Metabolism

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Type 1 diabetes mellitus (T1DM) is an autoimmune disease that targets the destruction of islet beta-cells resulting in insulin deficiency, hyperglycemia and death if untreated. Despite advances in medical devices and longer-acting insulin, there is still no robust therapy to substitute and protect beta-cells that are lost in T1DM. Attempts to refrain from the autoimmune attack have failed to achieve glycemic control in patients highlighting the necessity for a paradigm shift in T1DM treatment. Paradoxically, beta-cells are present in T1DM patients indicating a disturbed equilibrium between the immune attack and beta-cell regeneration reminiscent of unresolved wound healing that under normal circumstances progression towards an anti-inflammatory milieu promotes regeneration. Thus, the ultimate T1DM therapy should concomitantly restore immune self-tolerance and replenish the beta-cell mass similar to wound healing. Recently the agonistic activation of the nuclear receptor LRH-1/ NR5A2 was shown to induce immune self-tolerance, increase beta-cell survival and promote regeneration through a mechanism of alpha-to-beta cell phenotypic switch. This trans-regeneration process appears to be facilitated by a pancreatic anti-inflammatory environment induced by LRH-1/NR5A2 activation. Herein, we review the literature on the role of LRH1/NR5A2 in immunity and islet physiology and propose that a cross-talk between these cellular compartments is mandatory to achieve therapeutic benefits.

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confidence: 99%

Time for a paradigm shift in treating type 1 diabetes mellitus: coupling inflammation to islet regeneration

Cobo-Vuilleumier

Gauthier

2020

Metabolism

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“…The natural history of autoantibody development is well described in human T1D, with insulin or GAD65 autoantibodies typically appearing first in childhood and IA-2 and ZnT8 often occurring closer to disease onset and in combination with other autoantibodies [21]. Positivity for GAD65 and IA-2 autoantibodies decreases over time in humans following T1D onset [22].…”

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confidence: 99%

Evaluation for type 1 diabetes associated autoantibodies in diabetic and non-diabetic Australian terriers and Samoyeds

O'Kell

Wasserfall

Henthorn

et al. 2020

Canine Genet Epidemiol

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Background: Evidence for an autoimmune etiology in canine diabetes is inconsistent and could vary based on breed. Previous studies demonstrated that small percentages of diabetic dogs possess autoantibodies to antigens known to be important in human type 1 diabetes, but most efforts involved analysis of a wide variety of breeds. The objective of this study was to evaluate the presence of glutamic acid decarboxylase 65 (GAD65), insulinomaassociated protein 2 (IA-2), and zinc transporter 8 (ZnT8) autoantibodies in diabetic and non-diabetic Australian Terriers and Samoyeds, two breeds with comparatively high prevalence of diabetes, in the United States. Results: There was no significant difference in the proportion of samples considered positive for GAD65 or ZnT8 autoantibodies in either breed evaluated, or for IA-2 autoantibodies in Australian Terriers (p > 0.05). The proportion of IA-2 autoantibody positive samples was significantly higher in diabetic versus non-diabetic Samoyeds (p = 0.003), but substantial overlap was present between diabetic and non-diabetic groups. Conclusions: The present study does not support GAD65, IA-2, or ZnT8 autoantibodies as markers of autoimmunity in canine diabetes in Samoyeds or Australian Terriers as measured using human antigen sandwich enzyme-linked immunosorbent (ELISA) assays. Future studies using canine specific assays as well as investigation for alternative markers of autoimmunity in these and other canine breeds are warranted.

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“…Diese unterscheiden sich auch hinsichtlich des Risikos einer raschen Stadienprogredienz. Mathematische Algorithmen werden entwickelt, um Modelle komplexer, longitudinaler Antikörperprofile abzubilden und die Progressionsraten zu stratifizieren [ 8 ]. Metabolische Marker wie der orale Glukosetoleranztest und Verlaufsparameter wie das HbA 1c (glykiertes Hämoglobin A 1c ) sind weiterhin unerlässlich [ 7 ], um den individuellen Zeitpunkt der Manifestation abschätzen zu können, aber auch das kontinuierliche Glukosemonitoring wurde in Studien schon bei Patienten im Frühstadium erfolgreich eingesetzt [ 30 ].…”

Section: Früherkennung Durch Immundiagnostikunclassified

Typ-1-Diabetes: Früherkennung und Ansätze zur Prävention

2020

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Typ-1-Diabetes ist die häufigste chronische Stoffwechselerkrankung im Kindes-und Jugendalter, mit seit Jahren rasch zunehmender Inzidenz, insbesondere bei sehr jungen Kindern. Im asymptomatischen Frühstadium lassen sich schon im Kleinkindalter Inselautoantikörper nachweisen. Die ersten Lebensjahre sind daher entscheidend für Ansätze zur Primärprävention, v. a. bei Säuglingen mit genetischer Prädisposition. Die frühe Diagnosestellung verhindert Komplikationen bei der Manifestation und ermöglicht Kindern aus bisher nicht betroffenen Familien die Teilnahme an klinischen Studien zur Sekundärprävention.

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Birth and coming of age of islet autoantibodies

Cited by 38 publications

References 149 publications

Time for a paradigm shift in treating type 1 diabetes mellitus: coupling inflammation to islet regeneration

Time for a paradigm shift in treating type 1 diabetes mellitus: coupling inflammation to islet regeneration

Evaluation for type 1 diabetes associated autoantibodies in diabetic and non-diabetic Australian terriers and Samoyeds

Typ-1-Diabetes: Früherkennung und Ansätze zur Prävention

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