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Item Can Influenza Vaccine Modify COVID-19 Clinical Course?(Elsevier, 2020-09) Eldanasory, Omar Abdelhay; Rabaan, Ali A.; Al-Tawfiq, Jaffar A.; Medicine, School of MedicineItem Distinct serum immune profiles define the spectrum of acute and chronic pancreatitis from the multi-center PROCEED study(AGA, 2023-07) Lee, Bomi; Jones, Elaina K.; Manohar, Murli; Li, Liang; Yadav, Dhiraj; Conwell, Darwin L.; Hart, Phil A.; Vege, Santhi Swaroop; Fogel, Evan L.; Serrano, Jose; Anderson, Dana; Bellin, Melena D.; Topazian, Mark D.; Van Den Eeden, Stephen K.; Pandol, Stephen J.; Forsmark, Chris E.; Fisher, William E.; Park, Walter G.; Husain, Sohail Z.; Habtezion, Aida; Medicine, School of MedicineBackground & Aims Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis. Methods Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium. Samples (N = 231) were obtained from individuals without pancreatic disease (n = 56) and from those with chronic abdominal pain (CAP) (n = 24), AP (n = 38), RAP (n = 56), and CP (n = 57). Results A total of 33 immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to interleukin (IL) 17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL17A and C-C motif chemokine ligand 20 differentiated CP from CAP, suggesting the involvement of T helper 17 cells in CP pathogenesis. The receiver operator characteristic curve with 2 immune markers (IL17A and sulfotransferase 1A1) could differentiate CP from CAP (optimistic area under the curve = 0.78). The macrophage classical activation pathway elevated along the continuum of pancreatitis, suggesting an accumulation of proinflammatory signals over disease progression. Several immune markers were associated with smoking, alcohol, and diabetes status. Conclusions Immune profiling of serum samples from a large pancreatitis cohort led to identifying distinct immune markers that could serve as potential biomarkers to differentiate the varying pancreatitis disease states. In addition, the finding of IL17 signaling in CP could provide insight into the immune mechanisms underlying disease progression.Item Iron Administration, Infection, and Anemia Management in CKD: Untangling the Effects of Intravenous Iron Therapy on Immunity and Infection Risk(Elsevier, 2020-03-27) Ganz, Tomas; Aronoff, George R.; Gaillard, Carlo A. J. M.; Goodnough, Lawrence T.; Macdougall, Iain C.; Mayer, Gert; Porto, Graça; Winkelmayer, Wolfgang C.; Wish, Jay B.; Medicine, School of Medicinedysfunction, increased exposure to infectious agents, loss of cutaneous barriers, comorbid conditions, and treatment-related factors (eg, hemodialysis and immunosuppressant therapy). Because iron plays a vital role in pathogen reproduction and host immunity, it is biologically plausible that intravenous iron therapy and/or iron deficiency influence infection risk in CKD. Available data from preclinical experiments, observational studies, and randomized controlled trials are summarized to explore the interplay between intravenous iron and infection risk among patients with CKD, particularly those receiving maintenance hemodialysis. The current evidence base, including data from a recent randomized controlled trial, suggests that proactive judicious use of intravenous iron (in a manner that minimizes the accumulation of non–transferrin-bound iron) beneficially replaces iron stores while avoiding a clinically relevant effect on infection risk. In the absence of an urgent clinical need, intravenous iron therapy should be avoided in patients with active infection. Although serum ferritin concentration and transferrin saturation can help guide clinical decision making about intravenous iron therapy, definition of an optimal iron status and its precise determination in individual patients remain clinically challenging in CKD and warrant additional study.Item Novel genetic variants of PIP5K1C and MVB12B of the endosome-related pathway predict cutaneous melanoma-specific survival(e-Century Publishing, 2020-10) Lu, Guiqing; Zhou, Bingrong; He, Yuanmin; Liu, Hongliang; Luo, Sheng; Amos, Christopher I.; Lee, Jeffrey E.; Yang, Keming; Qureshi, Abrar; Han, Jiali; Wei, Qingyi; Epidemiology, School of Public HealthEndosomes regulate cell polarity, adhesion, signaling, immunity, and tumor progression, which may influence cancer outcomes. Here we evaluated associations between 36,068 genetic variants of 228 endosome-related pathway genes and cutaneous melanoma disease-specific survival (CMSS) using genotyping data from two previously published genome-wide association studies. The discovery dataset included 858 CM patients with 95 deaths from The University of Texas MD Anderson Cancer Center, and the replication dataset included 409 CM patients with 48 deaths from the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). In multivariate Cox proportional hazards regression analysis, we found that two novel SNPs (PIP5K1C rs11666894 A>C and MVB12B rs12376285 C>T) predicted CMSS, with adjusted hazards ratios of 1.47 (95% confidence interval = 1.15-1.89 and P = 0.002) and 1.73 (1.30-2.31 and 0.0002), respectively. Combined analysis of risk genotypes of these two SNPs revealed a dose-dependent decrease in CMSS associated with an increased number of risk genotypes (P trend = 0.0002). Subsequent expression quantitative trait loci (eQTL) analysis revealed that PIP5K1C rs11666894 was associated with mRNA expression levels in lymphoblastoid cell lines from 373 European descendants (P<0.0001) and that MVB12B rs12376285 was associated with mRNA expression levels in cultured fibroblasts from 605 European-Americans (P<0.0001). Our findings suggest that novel genetic variants of PIP5K1C and MVB12B in the endosome-related pathway genes may be promising prognostic biomarkers for CMSS, but these results need to be validated in future larger studies.