Chromogranin A is a T cell antigen in human type 1 diabetes.

Chromogranin A (ChgA) is a beta cell secretory granule protein and a peptide of ChgA, WE14, was recently identified as a ligand for diabetogenic CD4 T cell clones derived from the NOD mouse. In this study we compared responses of human CD4 T cells from recent onset type 1 diabetic (T1D) and control subjects to WE14 and to an enzymatically modified version of this peptide. T cell responders to antigens were detected in PBMCs from study subjects by an indirect CD4 ELISPOT assay for IFN-γ. T1D patients (n = 27) were recent onset patients within one year of diagnosis, typed for HLA-DQ8. Controls (n = 31) were either 1st degree relatives with no antibodies or from the HLA-matched general population cohort of DAISY/TEDDY. A second cohort of patients (n = 11) and control subjects (n = 11) was tested at lower peptide concentrations. We found that WE14 is recognized by T cells from diabetic subjects vs. controls in a dose dependent manner. Treatment of WE14 with transglutaminase increased reactivity to the peptide in some patients. This work suggests that ChgA is an important target antigen in human T1D subjects and that post-translational modification may play a role in its reactivity and relationship to disease.

The latent tuberculosis infection cascade of care during the COVID-19 pandemic response in a Mid-Sized US city.

Background: The COVID-19 pandemic response may unintentionally disrupt multiple public health services, including tuberculosis control programs. We aimed to assess differences in the cascade of care for latent tuberculosis infection (LTBI) in a Midwest U.S. city during the COVID-19 pandemic response. Methods: We conducted a retrospective cohort study of adult patients who presented for LTBI evaluation at the Hamilton County Public Health Tuberculosis Clinic in Ohio between 2019 and 2020. The pre-COVID-19 response period was defined as 01/2019 to 02/2020, and the COVID-19 pandemic response period (first wave) was defined as 04/2020 to 12/2020. We reviewed electronic medical records to extract sociodemographic information, medical history, follow-up and treatment data to define steps within the LTBI cascade of care. Logistic regressions were used to assess factors associated with LTBI treatment acceptance and completion, adjusted by potential confounders and COVID-19 period. Results: Data from 312 patients were included. There was a significant decrease in the number of monthly LTBI referrals (median, 18 vs. 8, p = 0.02) and LTBI evaluations (median, 17.5 vs. 7, p < 0.01) during the first wave of COVID-19. The proportion for whom immigration was listed as the indication for LTBI testing also declined (30% vs. 9%; p < 0.01) during COVID-19. More LTBI diagnoses were based on interferon-gamma release assay (IGRA; 30% vs. 49%; p < 0.01) during the COVID-19 response period. The proportion of people in the clinic for whom treatment for LTBI was recommended was similar before and during COVID-19 (76% vs. 81%, p = 0.41), as was LTBI treatment acceptance rates (56% vs. 64%, p = 0.28), and completion rates (65% vs. 63%, p = 0.85). In multivariate analysis, LTBI treatment acceptance was associated with Hispanic ethnicity, younger age, male sex, IGRA being used for diagnosis, and non-healthcare occupation, independent of COVID-19 period. LTBI treatment completion was associated with taking a rifamycin-containing regimen, independent of COVID-19 period. Conclusion: We observed a significant decline in the number of monthly LTBI referrals and evaluations during the first wave of COVID-19, revealing an unintended negative impact of the COVID-19 response in our region. However, LTBI treatment acceptance and completion rates were not affected during COVID-19.