Browsing by Subject "immunosuppression"

Now showing 1 - 7 of 7
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    Behaviors, symptoms, and outcomes of North American patients with autoimmune hepatitis during the COVID-19 pandemic
    (BMJ, 2021-12) Vuppalanchi, Vahin; Gelow, Kayla; Vuppalanchi, Raj; Lammert, Craig; Green, Kelsey; Medicine, School of Medicine
    The management of patients with autoimmune hepatitis (AIH) in the era of SARS-CoV-2 is challenging given minimal published clinical data. We used a large cohort of patients with AIH across the USA to investigate the differences in known risk factors for severe SARS-CoV-2 and AIH characteristics among patients who experienced symptoms consistent with COVID-19 illness versus those who did not. Additionally, we explored the effect of living through the SARS-CoV-2 pandemic on the extrahepatic symptoms and behaviors of patients with AIH. An invitation to complete a COVID-19-specific questionnaire was publicized in well-established social media cohorts of patients with AIH. Eligibility criteria were age ≥18 years, US residency, and an AIH diagnosis by a physician. A total of 420 individuals were eligible for the study. Symptoms consistent with COVID-19 were reported in 11% (n=48) with 3 patients requiring hospitalizations. Body mass index (BMI) >40 kg/m2 (23% vs 10%, p=0.01) and exposure to house (33% vs 3%, p=0.0001) or work (38% vs 17%, p=0.02) contacts with COVID-19 were factors found higher in those with symptoms. Cirrhosis or steroid use or immunosuppression was not significantly different between symptomatic and non-symptomatic groups. Worsening fatigue (45% vs 30%, p=0.06), anxiety (89% vs 70%, p=0.08), and itch (40% vs 18%, p=0.03) were more common among those reporting COVID-19 symptoms compared with those without. BMI >40 kg/m2 and exposure to contacts with COVID-19 illness but not cirrhosis or immunosuppression were associated with increased risk of COVID-19 illness in patients with AIH.
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    Clinical characteristics, outcomes and immunosuppression strategies of heart transplant recipients infected with covid-19
    (Elsevier, 2021) Ilonze, Onyedika J.; Ballut, Kareem; Jones, Mark; Rao, Roopa; Guglin, Maya; Medicine, School of Medicine
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    Cold agglutinin-mediated autoimmune haemolytic anaemia associated with diffuse large B cell lymphoma
    (BMJ, 2018-07-10) Wongsaengsak, Sariya; Czader, Magdalena; Suvannasankha, Attaya; Medicine, School of Medicine
    Cold agglutinin-mediated autoimmune haemolytic anaemia is associated with the development of autoantibodies that can agglutinate red blood cells at cold temperatures. While primary cold agglutinin disease is an idiopathic lymphoproliferative disorder, secondary cold agglutinin syndrome (CAS) complicates other diseases such as infections, autoimmune diseases and cancers, mostly low-grade lymphomas. Early recognition, treatment of CAS and treatment of its associated underlying diseases are crucial to a successful outcome. We report a case of CAS in a setting of diffuse large B cell lymphoma, in which the treatment course was complicated by worsened anaemia due to chemotherapy-induced myelosuppression. We reviewed previously reported cases and discussed diagnosis and treatment strategies, including novel complement inhibitors, as potential future therapy.
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    Epidermal PPARγ influences subcutaneous tumor growth and acts through TNF-α to regulate contact hypersensitivity and the acute photoresponse
    (Impact Journals, 2017-09-18) Konger, Raymond L.; Derr-Yellin, Ethel; Travers, Jeffrey B.; Ocana, Jesus A.; Sahu, Ravi P.; Pathology and Laboratory Medicine, School of Medicine
    It is known that ultraviolet B (UVB) induces PPARγ ligand formation while loss of murine epidermal PPARγ (Pparg-/-epi) promotes UVB-induced apoptosis, inflammation, and carcinogenesis. PPARγ is known to suppress tumor necrosis factor-α (TNF-α) production. TNF-α is also known to promote UVB-induced inflammation, apoptosis, and immunosuppression. We show that Pparg-/-epi mice exhibit increased baseline TNF-α expression. Neutralizing Abs to TNF-α block the increased photo-inflammation and photo-toxicity that is observed in Pparg-/-epi mouse skin. Interestingly, the increase in UVB-induced apoptosis in Pparg-/-epi mice is not accompanied by a change in cyclobutane pyrimidine dimer clearance or in mutation burden. This suggests that loss of epidermal PPARγ does not result in a significant alteration in DNA repair capacity. However, loss of epidermal PPARγ results in marked immunosuppression using a contact hypersensitivity (CHS) model. This impaired CHS response was significantly alleviated using neutralizing TNF-α antibodies or loss of germline Tnf. In addition, the PPARγ agonist rosiglitazone reversed UVB-induced systemic immunosuppression (UV-IS) as well as UV-induced growth of B16F10 melanoma tumor cells in syngeneic mice. Finally, increased B16F10 tumor growth was observed when injected subcutaneously into Pparg-/-epi mice. Thus, we provide novel evidence that epidermal PPARγ is important for cutaneous immune function and the acute photoresponse.
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    Eruptive Disseminated Porokeratosis Associated with Corticosteroid-Induced Immunosuppression
    (Wiley, 2015-10) Bednarek, Robert; Ezra, Navid; Toubin, Yulianna; Linos, Konstantinos; Mousdicas, Nico; Department of Dermatology, IU School of Medicine
    Eruptive disseminated porokeratosis (EDP) is a disease that presents clinically with sudden onset of erythematous papules and plaques, with a ridge-like border histologically represented by a cornoid lamella. We report a case of EDP occurring in a 39-year-old woman 3 days after completion of a 2-week course of oral corticosteroid therapy for an acute asthma exacerbation. The patient was treated with emollients and sun protection. Unlike the more chronic disseminated superficial (actinic) porokeratosis, EDP secondary to immunosuppression from corticosteroid therapy has very rarely been reported in the dermatological literature.
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    Plasmodium Impairs Antibacterial Innate Immunity to Systemic Infections in Part Through Hemozoin-Bound Bioactive Molecules
    (Frontiers, 2020-06-30) Harding, Christopher L.; Villarino, Nicolas F.; Valente, Elena; Schwarzer, Evelin; Schmidt, Nathan W.; Pediatrics, School of Medicine
    One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through heme-oxygenase I (HO-I)-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during both acute parasitemia and up to 2 months after clearance of Py infected red blood cells that was independent of HO-I and IL-10. Py-infected mice were also susceptible to Streptococcus pneumoniae (Sp) bacteremia, a common malaria-bacteria co-infection, with higher blood and spleen bacterial burdens and decreased survival compared to naïve mice. Mechanistically, impaired immunity to Sp was independent of HO-I, but was dependent on Py-induced IL-10. Splenic phagocytes from Py infected mice exhibit an impaired ability to restrict growth of intracellular Lm, and neutrophils from Py-infected mice produce less reactive oxygen species (ROS) in response to Lm or Sp. Analysis also identified a defect in a serum component in Py-infected mice that contributes to reduced production of ROS in response to Sp. Finally, treating naïve mice with Plasmodium-derived hemozoin containing naturally bound bioactive molecules, excluding DNA, impaired clearance of Lm. Collectively, we have demonstrated that Plasmodium infection impairs host immunity to diverse bacteria, including S. pneumoniae, through multiple effects on innate immunity, and that a parasite-specific factor (Hz+bound bioactive molecules) directly contributes to Plasmodium-induced suppression of antibacterial innate immunity.
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    Steroid Free Three Drug Maintenance Regimen for Pancreas Transplant Alone: Comparison of Induction with Rabbit Antithymocyte Globulin +/- Rituximab
    (Wiley, 2018) Fridell, Jonathan; Mangus, Richard; Chen, Jeanne; Taber, Tim; Cabrales, Arianna E.; Sharfuddin, Asif; Yaqub, Muhammad; Powelson, John; Surgery, School of Medicine
    Graft survival following pancreas transplant alone (PTA) is inferior to other pancreas transplants. Steroid elimination is appealing, but a two drug maintenance strategy may be inadequate. Additionally, recipients tend to have diabetic nephropathy and do not tolerate nephrotoxic medications. A three‐drug maintenance strategy permits immunosuppression through different mechanisms as well as an opportunity to use lower doses of the individual medications. Induction consisted of five doses of rabbit antithymocyte globulin (1 mg/kg/dose). As of October 2007, a single dose of rituximab (150 mg/m2) was added. Maintenance consisted of tacrolimus, sirolimus and mycophenolate mofetil. From 2004 to 2017, 166 PTA were performed. Graft loss at 7‐ and 90‐ days were 4% and 5%, and one year patient and graft survival were 97% and 91%. Comparing induction without and with rituximab, there was no significant difference in 7 or 90 day graft loss, 1 year patient or graft survival or in the rate of rejection or infection. Rabbit antithymocyte globulin induction and steroid withdrawal followed by a three drug immunosuppression regimen is an excellent strategy for PTA recipients.