Association of PD-1 and PD-L1 Genetic Polymorphyisms with Type 1 Diabetes Susceptibility

Qian, Chenyue; Guo, Heming; Chen, Xiaohong; Shi, Aiming; Li, Sicheng; Wang, Xin; Pan, Jie; Chen, Fang

doi:10.1155/2018/1614683

Cited by 31 publications

(32 citation statements)

References 29 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Instead, the allele of HLA A ∗ 0201 in this patient was reported to be relevant with diabetes susceptibility ( 4 ), which has not been reported in the onset diabetes by anti-PD-1 treatment. In addition, studies about genetic polymorphisms within PDCD1 (encoding PD-1) identified single nucleotide polymorphisms (SNPs) of rs111568821, rs2227981, rs2227982, and rs4143815 as significantly associated with type 1 diabetes susceptibility ( 15 , 16 ). Combined ICB treatment might also carry an increased risk of diabetes compared with that of monotherapy.…”

Section: Discussionmentioning

confidence: 99%

Sintilimab-Induced Autoimmune Diabetes in a Patient With the Anti-tumor Effect of Partial Regression

et al. 2020

View full text Add to dashboard Cite

Context: Immune checkpoint blockades (ICBs) have been approved widely to treat various malignancies. Autoimmune diabetes mellitus, which can be caused by programmed cell death protein 1 (PD-1) inhibitors, is rare. Sintilimab, a monoclonal anti-PD-1 antibody, has been approved in China for the treatment of Hodgkin's lymphoma and was used in our clinical trial for patients with unresectable hepatocellular carcinoma (HCC). Case Presentation: We present the first case of autoimmune diabetes during Sintilimab treatment in a patient with unresectable HCC, accompanied by a remarkable anti-tumor effect of partial regression. A 56-year-old male with typical symptoms presented with diabetic ketoacidosis (DKA) at 24 weeks after Sintilimab initiation. His fasting plasma glucose level was 22.2 mmol/L, HbA1c was 7.8%, fasting insulin was 1.5 mIU/L, and fasting C-peptide was 1.12 ng/mL, which further decreased to 0.21 ng/mL 4 days later. The patient was diagnosed with new-onset diabetes mellitus using the oral glucose tolerance test. The anti-glutamic acid decarboxylase 65 antibody, anti-islet cell antibody, and anti-insulin antibody tests were all negative. For the type 1 diabetes-associated alleles of human leukocyte antigen (HLA) class I and II, the most relevant type was identified as HLA-A * 0201. A diagnosis of PD-1 inhibitor-induced autoimmune diabetes was made. After rectification of DKA, he was treated with insulin therapy daily, which has since controlled his plasma glucose well. Thereafter, Sintilimab was been continued with sustained therapeutic effect. Conclusion: Due 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.

show abstract

Section: Discussionmentioning

confidence: 99%

Sintilimab-Induced Autoimmune Diabetes in a Patient With the Anti-tumor Effect of Partial Regression

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Additionally, recent studies have reported that a single-nucleotide polymorphism (SNP) in PDCD1 is associated with the development of autoimmune diseases (SLE, type 1 diabetes, progressive MS, Vogt-Koyanagi-Harada disease, Graves' disease, and RA), suggesting that PDCD1 may be involved in the maintenance of tolerance (20, 108). For instance, the SNP rs4143815 in PD-L1 is associated with T1DM and could be a new biomarker for predicting T1DM susceptibility (109, 110).…”

Section: Autoimmunitymentioning

confidence: 99%

The Diverse Function of PD-1/PD-L Pathway Beyond Cancer

et al. 2019

View full text Add to dashboard Cite

The recent success of PD-1 and PD-L1 blockade in cancer therapy illustrates the important role of the PD-1/PD-L1 pathway in the regulation of antitumor immune responses. However, signaling regulated by the PD-1/PD-L pathway is also associated with substantial inflammatory effects that can resemble those in autoimmune responses, chronic infection, and sepsis, consistent with the role of this pathway in balancing protective immunity and immunopathology, as well as in homeostasis and tolerance. Targeting PD-1/PD-L1 to treat cancer has shown benefits in many patients, suggesting a promising opportunity to target this pathway in autoimmune and inflammatory disorders. Here, we systematically evaluate the diverse biological functions of the PD-1/PD-L pathway in immune-mediated diseases and the relevant mechanisms that control these immune reactions.

show abstract

“…Within the context of T1D, the PD-1/PD-L1 axis is pivotal to autoimmunity, as seen by abnormalities in PD-L1 presentation in human patients with T1D ( 14 ) and disease halting in transgenic models expressing PD-L1 ( 15 ). Strategies aimed at using PD-L1 to control disease progression and diabetes reversal have ranged from genetically modifying islets to express PD-L1 ( 16 ) to improve graft survival in allogeneic transplantation models ( 17 ) to the delivery of antigen-presenting cells genetically or chemically modified to overexpress PD-L1 ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy via PD-L1–presenting biomaterials leads to long-term islet graft survival

et al. 2020

View full text Add to dashboard Cite

Antibody-mediated immune checkpoint blockade is a transformative immunotherapy for cancer. These same mechanisms can be repurposed for the control of destructive alloreactive immune responses in the transplantation setting. Here, we implement a synthetic biomaterial platform for the local delivery of a chimeric streptavidin/programmed cell death-1 (SA-PD-L1) protein to direct “reprogramming” of local immune responses to transplanted pancreatic islets. Controlled presentation of SA-PD-L1 on the surface of poly(ethylene glycol) microgels improves local retention of the immunomodulatory agent over 3 weeks in vivo. Furthermore, local induction of allograft acceptance is achieved in a murine model of diabetes only when receiving the SA-PD-L1–presenting biomaterial in combination with a brief rapamycin treatment. Immune characterization revealed an increase in T regulatory and anergic cells after SA-PD-L1-microgel delivery, which was distinct from naïve and biomaterial alone microenvironments. Engineering the local microenvironment via biomaterial delivery of checkpoint proteins has the potential to advance cell-based therapies, avoiding the need for systemic chronic immunosuppression.

show abstract

Association of PD-1 and PD-L1 Genetic Polymorphyisms with Type 1 Diabetes Susceptibility

Cited by 31 publications

References 29 publications

Sintilimab-Induced Autoimmune Diabetes in a Patient With the Anti-tumor Effect of Partial Regression

Sintilimab-Induced Autoimmune Diabetes in a Patient With the Anti-tumor Effect of Partial Regression

The Diverse Function of PD-1/PD-L Pathway Beyond Cancer

Immunotherapy via PD-L1–presenting biomaterials leads to long-term islet graft survival

Contact Info

Product

Resources

About