Rapid onset type 1 diabetes with anti-PD-1 directed therapy.

Rapid onset type 1 diabetes with anti-PD-1 directed therapy. Oncotarget. 2020 Jul 14;11(28):2740-2746 Authors: Yun K, Daniels G, Gold K, Mccowen K, Patel SP Abstract Type 1 diabetes is a rare immune-related adverse event (irAE) caused by checkpoint inhibitors with serious risk for diabetic ketoacidosis (DKA). Using our electronic medical record, we identified 1327 adult patients who received PD-(L)1 or CTLA-4 inhibitors from 2013 to 2018. Of the patients who received immunotherapy, 5 (0.38%) patients were found to have type 1 diabetes, all of whom presented with DKA requiring insulin at 20 to 972 days from their first anti-PD-(L)1 dose. All patients were treated with anti-PD-1 therapy (nivolumab or pembrolizumab). Four patients had new onset diabetes with mean HbA1c of 9.1% on DKA presentation and persistent elevations over time. Two patients who tested positive for glutamic acid decarboxylase (GAD) antibodies presented with DKA at 20 and 106 days from first anti-PD-1 administration whereas patients who were autoantibody negative had DKA more than a year later. Type 1 diabetes occurs within a wide time frame after anti-PD-1 initiation and commences with an abrupt course. Our case series suggests that monitoring glycemia in patients on PD-1 inhibitors is not predictive for diabetes occurrence. GAD autoantibodies could portend earlier onset for diabetes, although further prospective studies are needed to elucidate their diagnostic utility and contribution i...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

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CONCLUSION: In cSLE, PA is associated with more hospitalizations and aggressive immunotherapy use. Although lupus disease activity improved over time, patients' QoL neither improved over time nor differed by having other autoimmune disease. Prospective, case-control, long-term follow-up studies on cSLE are needed to validate our results. MESH KEY INDEXING TERMS: Pediatric systemic lupus erythematosus; Autoimmune diseases; Outcome assessment. PMID: 33016198 [PubMed - as supplied by publisher]
Source: Lupus - Category: Rheumatology Authors: Tags: Lupus Source Type: research
Abstract Over the past four decades, the number of people with Type 1 Diabetes (T1D) has increased by 4% per year, making it an important public health challenge. Currently, no curative therapy exists for T1D and the only available treatment is insulin replacement. HLA-DQ8 has been shown to present antigenic islet peptides driving the activation of CD4+ T-cells in T1D patients. Specifically, the insulin peptide InsB:9-23 activates self-reactive CD4+ T-cells, causing pancreatic beta cell destruction. The aim of the current study was to identify retro-inverso-d-amino acid based peptides (RI-D-peptides) that can supp...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research
In conclusions, ICI-induced type 1 diabetes is a potentially life-threating adverse event after the immunotherapy of cancers. Screening and early recognition is important. Further investigation of the mechanism may help to better understand the pathology of type 1 diabetes. PMID: 32842016 [PubMed - as supplied by publisher]
Source: Chinese Medical Journal - Category: General Medicine Authors: Tags: Chin Med J (Engl) Source Type: research
ConclusionDue to unpredictability of this rare immune related adverse event (irAE), diabetes-related autoantibodies and C-peptide are recommended to be tested before immunotherapy, and plasma glucose monitoring should be performed. After plasma glucose is well controlled using insulin therapy, PD-1 inhibitor treatment might be continued, especially when the immunotherapy is effective.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Authors: El-Mokhtar MA, Elsherbiny NM, Sayed D, Raafat DM, Askar E, Hussein A, Abdel-Malek MAY, Shalaby AM Abstract B regulatory cells (Breg) refer to characteristic subsets of B cells that generally exert anti-inflammatory functions and maintain peripheral tolerance mainly through their ability to secrete interleukin-10 (IL10). Dysregulation in the function of Breg cells was reported in several autoimmune diseases. However, the relation between Breg and children with type 1 diabetes (T1D) is poorly understood. Thus, this study is aimed at determining whether Breg cells play a role in T1D in children or not, so we ...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
ConclusionsThe current in vitro study provides strong evidence that PDLSCs seem to be a very promising source for overcoming the autoimmune destruction seen in T1D as they exerted an immunosuppressive effect on monocyte derived mDCs from patients with T1D. Additional studies should be conducted to further reveal the immunomodulatory and suppressive properties of PDLSCs and their potential use in immunotherapy for this disease.
Source: Journal of Diabetes and Metabolic Disorders - Category: Endocrinology Source Type: research
Conclusions/interpretationGAD65-specific immunotherapy has a significant effect on C-peptide retention in individuals with recent-onset type 1 diabetes who have theDR3-DQ2 haplotype.Graphical abstract
Source: Diabetologia - Category: Endocrinology Source Type: research
Purpose of review The role of T cells specific for islet autoantigens is proven in pathogenesis of type 1 diabetes. Recently, there has been rapid expansion in the number of T-cell subsets identified, this has coincided with an increase in the repertoire of reported islet antigens mainly through the discovery of novel epitopes. A discussion of how these marry together is now warranted and timely. Recent findings In this review, we will discuss the autoreactivity against neo-epitopes. We then explore the growing array of T-cell subsets for both CD4+ T cells, including follicular and peripheral T helper cells, and CD8+ ...
Source: Current Opinion in Endocrinology, Diabetes and Obesity - Category: Endocrinology Tags: DIABETES AND ENDOCRINE PANCREAS II: Edited by Peter A. Gottlieb Source Type: research
Purpose of review To summarize a new form of autoimmune diabetes as an adverse event of specific cancer immunotherapies. Immune checkpoint inhibitors are revolutionary treatments in advanced cancers; however, they can cause type 1 diabetes following treatment with these state-of-the-art therapies. Recent findings A review of the literature showed that this new form of autoimmune diabetes has significant similarities with childhood-onset type 1 diabetes but also some distinctions. It frequently presents with severe diabetic ketoacidosis and almost half of the patients have type 1 diabetes-associated antibodies at prese...
Source: Current Opinion in Endocrinology, Diabetes and Obesity - Category: Endocrinology Tags: DIABETES AND ENDOCRINE PANCREAS II: Edited by Peter A. Gottlieb Source Type: research
ConclusionImmune checkpoint inhibition was relatively well tolerated in a cohort of pediatric patients spanning several CNS tumor diagnoses. Results from prospective clinical trials will be critical to inform clinical decisions.
Source: Journal of Neuro-Oncology - Category: Cancer & Oncology Source Type: research
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