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Introduction: End-stage renal disease (ESRD) results in immune dysfunction that is characterized by both systemic inflammation and immune incompetence, leading to impaired responses to vaccination., Methods: To unravel the complex regulatory immune interplay in ESRD, we performed the network-based transcriptomic profiling of ESRD patients on maintenance hemodialysis (HD) and matched healthy controls (HCs) who received the two-dose regimen of the COVID-19 mRNA vaccine BNT162b2., Results: Co-expression networks based on blood transcription modules (BTMs) of genes differentially expressed between the HD and HC groups revealed co-expression patterns that were highly similar between the two groups but weaker in magnitude in the HD compared to HC subjects. These networks also showed weakened coregulation between BTMs within the dendritic cell (DC) family as well as with other BTM families involved with innate immunity. The gene regulatory networks of the most enriched BTMs, likewise, highlighted weakened targeting by transcription factors of key genes implicated in DC, natural killer (NK) cell, and T cell activation and function. The computational deconvolution of immune cell populations further bolstered these findings with discrepant proportions of conventional DC subtypes, NK T cells, and CD8+ T cells in HD subjects relative to HCs., Conclusion: Altogether, our results indicate that constitutive inflammation in ESRD compromises the activation of DCs and NK cells, and, ultimately, their mediation of downstream lymphocytes, leading to a delayed but intact immune response to mRNA vaccination.

Background: End-stage renal disease (ESRD) patients experience immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, underscores the need for examination of the immune response to the COVID-19 mRNA-based vaccines., Methods: The immune response to the COVID-19 BNT162b2 mRNA vaccine was assessed in 20 HD patients and cohort-matched controls. RNA sequencing of peripheral blood mononuclear cells was performed longitudinally before and after each vaccination dose for a total of six time points per subject. Anti-spike antibody levels were quantified prior to the first vaccination dose (V1D0) and 7 d after the second dose (V2D7) using anti-spike IgG titers and antibody neutralization assays. Anti-spike IgG titers were additionally quantified 6 mo after initial vaccination. Clinical history and lab values in HD patients were obtained to identify predictors of vaccination response., Results: Transcriptomic analyses demonstrated differing time courses of immune responses, with prolonged myeloid cell activity in HD at 1 wk after the first vaccination dose. HD also demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p<0.05). Anti-spike IgG remained elevated above baseline at 6 mo in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development., Conclusions: Overall, we demonstrate differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance HD subjects comparable to healthy controls and identify transcriptomic and clinical predictors of anti-spike IgG titers in HD. Analyzing vaccination as an in vivo perturbation, our results warrant further characterization of the immune dysregulation of ESRD., Funding: F30HD102093, F30HL151182, T32HL144909, R01HL138628. This research has been funded by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award UL1TR002003., Competing Interests: YC, KH, JL, CV, CA, MA, MG, CL, RE, YH, RC, NS, SW, SH, RG, BT, CS, MH, YC, JJ, WW, MR, PF, DP No competing interests declared, RN Received a grant from Janssen. The author has received consulting fees from Gilead and Viiv. The author has no other competing interests to declare, (© 2024, Chang, Huang et al.)

Background: Individuals with sarcoidosis are at higher risk for infection owing to underlying disease pathogenesis and need for immunosuppressive treatment. Current knowledge as to how subjects with sarcoidosis respond to different forms of vaccination is limited. We examined quantitative and functional antibody response to COVID-19 vaccination in infection-naive subjects with and without sarcoidosis., Methods: Our prospective cohort study recruited 14 subjects with biopsy-proven sarcoidosis and 27 age-sex matched controls who underwent a two-shot series of the BNT162b2 mRNA vaccine at the University of Illinois at Chicago. Baseline, 4-week and 6-month trimer spike protein IgG and neutralising antibody (nAb) titres were assessed. Correlation and multivariate regression analysis was conducted., Results: Sarcoidosis subjects had a significant increase in short-term antibody production to a level comparable to controls; however, IgG titres significantly declined back to baseline levels by 6 months. Corresponding neutralising assays revealed robust nAb titres in sarcoidosis subjects that persisted at 6 months. A significant and strong correlation between IgG and nAb titres across all time points was observed in the control group. However within the sarcoidosis group, a significant but weak correlation between antibody levels was found. Overall, IgG levels were poor predictors of nAb titres at short- or long-term time points., Conclusions: Sarcoidosis subjects exhibit nAb induced by the BNT162b2 mRNA SARS-CoV-2 vaccine at levels comparable to controls that persists at 6 months indicating conferred immunity. Trimer IgG levels are poor predictors of nAb in subjects with sarcoidosis. Studies of further antibody immunoglobulins and subtypes warrant investigation., Competing Interests: Conflict of interest: Richard M. Novak reports the following relationships outside the submitted work: grants or contracts received from Janssen; consulting fees received from Gilead and Viiv. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: Nontuberculous Mycobacterium -related pulmonary disease (NTM-PD) is commonly caused by Mycobacterium avium complex (MAC) and is increasingly recognized in veterans. NTM-PD carries an increased risk of mortality, and lack of treatment is an predictor of increased mortality., Methods: We describe the clinical characteristics of veterans diagnosed with MAC-pulmonary disease (MAC-PD) followed in a health care setting with varying treatment practices. We reviewed the electronic health records of veterans without HIV who had sputum culture-positive MAC-PD followed at the Jesse Brown Veteran Affairs Medical Center in Chicago, Illinois., Results: We identified 19 veterans diagnosed with MAC-PD between 2008 and 2019. They were predominantly male (89.5%), Black (73.6%), and had a median age of 74 years. Sixteen veterans (84.2%) had underlying lung disease, and 16 (84.2%) were current or former smokers. Respiratory symptoms were reported in 17 veterans (89.5%). Guideline-directed combination antimycobacterial therapy was initiated in 10 veterans (52.6%); however, only 5 (50.0%) completed treatment. Comorbidities, symptoms, and findings on chest imaging at diagnosis were similar among treated and untreated veterans., Conclusions: Clinical, imaging, and treatment attributes of MAC-PD in veterans without HIV who reside in metropolitan Chicago are heterogeneous and are associated with a relatively high mortality rate. Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article., (Copyright © 2022 Frontline Medical Communications Inc., Parsippany, NJ, USA.)