Checkpoint inhibitors (CPIs) targeting programmed death-1(PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) have revolutionized cancer treatment but can trigger autoimmune complications including CPI-induced diabetes (CPI-DM), which occurs preferentially with PD-1 blockade. We found evidence of pancreatic inflammation in patients with CPI-DM with shrinkage of pancreases, increased pancreatic enzymes, and in a case from a patient who died with CPI-DM, peri-islet lymphocytic infiltration.In the NOD mouse model, anti-PD-L1 but not anti-CTLA-4 induces diabetes rapidly. RNA sequencing revealed that cytolytic IFNγ+ CD8+ T cells infiltrated islets with anti-PD-L1. Changes in β cells were predominantly driven by IFNγ and TNFα and included induction of a potentially novel β cell population with transcriptional changes suggesting dedifferentiation. IFNγ increased checkpoint ligand expression and activated apoptosis pathways in human β cells in vitro. Treatment with anti-IFNγ and anti-TNFα prevented CPI-DM in anti-PD-L1 treated NOD mice. CPIs targeting the PD-1/PD-L1 pathway result in transcriptional changes in β cells and immune infiltrates that may lead to the development of diabetes. Inhibition of inflammatory cytokines can prevent CPI-DM, suggesting a strategy for clinical application to prevent this complication.

Background Persons with disabilities comprise more than one billion people in the world, yet they are one of the most discriminated groups and face significant health disparities. Particularly in developing countries, which contain 80% of the entire population with disabilities, these individuals experience major barriers in accessing sexual and reproductive health (SRH) services. Education is an important factor that greatly affects individuals’ SRH service utilization. Hence, we sought to investigate the relationship between education and SRH service utilization for persons with disabilities in Bangladesh. Methods Using an explanatory sequential mixed-methods design, a total of 5000 persons with disabilities were surveyed for the quantitative component and 15 mini-ethnographic case studies were conducted with persons with disabilities for the qualitative component. Chi-squared tests and logistic regression analyses were performed on the survey data, while the qualitative interviews were coded and their SRH themes synthesized accordingly. Results Our quantitative findings show that education statistically significantly increases persons with disabilities’ SRH service utilization of antenatal care, delivery care, postnatal care, and family planning (P < 0.05). Interestingly, for persons with disabilities, primary education shows increased adjusted odds of family planning use but is likely not enough to increase antenatal care, delivery care, or postnatal care use; secondary or post-secondary education may be required to improve utilization of these latter services. Qualitative findings support the association between higher education levels and greater SRH service use. Persons with disabilities of lower educational attainment held misinformation and distrust in SRH services and experienced mistreatment by SRH healthcare providers, discouraging them from seeking future SRH services. Conclusions We report that higher formal education level is associated with greater SRH service use for persons with disabilities in Bangladesh. Formally educating persons with disabilities expands their SRH knowledge and familiarity with SRH services, as well as leads to more economic opportunities so they can afford SRH services. Increasing formal education levels for persons with disabilities, paired with integrating comprehensive sexuality education (CSE) in their schools, will likely help close the gap in SRH health disparities for this vulnerable population.

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