Role of immune system in type 1 diabetes mellitus pathogenesis

Szablewski, Leszek

doi:10.1016/j.intimp.2014.06.033

Cited by 72 publications

(53 citation statements)

References 158 publications

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“…This process is attributed to infiltration of the pancreatic islets by autoreactive T cells, causing ‘insulitis’ [23]. The most widely used model to study this process is the non-obese diabetic (NOD) mouse.…”

Section: Discussionmentioning

confidence: 99%

Genetic risk analysis of a patient with fulminant autoimmune type 1 diabetes mellitus secondary to combination ipilimumab and nivolumab immunotherapy

Lowe

Perry

Salama

et al. 2016

j. immunotherapy cancer

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BackgroundCheckpoint inhibitor immunotherapy is becoming an effective treatment modality for an increasing number of malignancies. As a result, autoinflammatory side-effects are also being observed more commonly in the clinic. We are currently unable to predict which patients will develop more severe toxicities associated with these treatment regimens.Case presentationWe present a patient with stage IV melanoma that developed rapid onset autoimmune type 1 diabetes (T1D) in response to combination ipilimumab and nivolumab immunotherapy. At the time of the patient’s presentation with diabetes ketoacidosis, a confirmed anti-GAD antibody seroconversion was noted. Longer-term follow-up of this patient has demonstrated a durable complete response based on PET CT imaging along with a persistently undetectable C-peptide level. Single nucleotide polymorphism gene sequencing and HLA risk allele analysis has revealed the patient to lack any established genetic predisposition to the development of autoimmune T1D.ConclusionsWhile larger studies are necessary to better understand the role of genetic risk factors for the development of autoimmune toxicities in those patients undergoing checkpoint inhibitor immunotherapy, these results suggest that pre-screening patients for known T1D risk alleles may not be indicated. Additional investigation is needed to determine whether an approach such as T cell receptor clonotypic analysis to identify the presence of autoreactive T cell clones may be an effective approach for predicting which patients are at risk for the development of autoinflammatory toxicities while undergoing checkpoint inhibitor immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Genetic risk analysis of a patient with fulminant autoimmune type 1 diabetes mellitus secondary to combination ipilimumab and nivolumab immunotherapy

Lowe

Perry

Salama

et al. 2016

j. immunotherapy cancer

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show abstract

“…▪MSCs suppress β cell-specific T cells response. [13,88,89] RA ▪ Increased Th1, Th17 cells and decreased Treg cells in inflammatory synovial milieu. ▪Activated B cells produce autoantibodies, cytokines.…”

Section: Diseasesmentioning

confidence: 99%

Mesenchymal stem cells and adaptive immune responses

Cao

et al. 2015

Immunology Letters

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“…Individuals with diminished immune responses from inborn or acquired causes have an increased susceptibility to infections (Blot et al, 2002; Clark and Hajjeh, 2002; Fishman, 2007; Fishman and Rubin, 1998; McNeil et al, 2001). Conversely, individuals with an overactive immune system are more susceptible to autoimmune diseases such as rheumatoid arthritis, type 1 diabetes and multiple sclerosis, and inflammatory diseases such as gout, Crohn’s disease, and atherosclerosis (Gandhi et al, 2010; Martinon, 2010; Szablewski, 2014). Variability in the immune responses also influences susceptibility to other important pathologies such as malignant processes (de Visser et al, 2006) and neurodegenerative diseases like Parkinson’s disease and Alzheimer disease (Heneka et al, 2015; Mosley et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Host and Environmental Factors Influencing Individual Human Cytokine Responses

Horst

Jaeger

Smeekens

et al. 2016

Cell

377

386

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Summary Differences in susceptibility to immune-mediated diseases are determined by variability in immune responses. In three studies within the Human Functional Genomics Project we assessed the effect of environmental and non-genetic host factors, of the genetic make-up of the host, and of the intestinal microbiome, on the cytokine responses in humans. We analyzed the association of these factors with circulating mediators and with six cytokines after stimulation with 19 bacterial, fungal, viral and non-microbial metabolic stimuli in 534 healthy subjects. In this first study we show a strong impact of non-genetic host factors (e.g. age and gender) on cytokine production and circulating mediators. Additionally, annual seasonality is found to be an important environmental factor influencing cytokine production. Alpha-1-antitrypsin concentrations partially mediate the seasonality of cytokine responses, whereas the effect of vitamin D levels is limited. The complete dataset has been made publicly available as a comprehensive resource for future studies.

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Role of immune system in type 1 diabetes mellitus pathogenesis

Cited by 72 publications

References 158 publications

Genetic risk analysis of a patient with fulminant autoimmune type 1 diabetes mellitus secondary to combination ipilimumab and nivolumab immunotherapy

Genetic risk analysis of a patient with fulminant autoimmune type 1 diabetes mellitus secondary to combination ipilimumab and nivolumab immunotherapy

Mesenchymal stem cells and adaptive immune responses

Host and Environmental Factors Influencing Individual Human Cytokine Responses

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