Mechanisms Involved in Hypersensitivity Reactions to Polysulfone Hemodialysis Membranes Aranzazu Rodr  ıguez-Sanz, Rafael S anchez-Villanueva, Javier Dom  ınguez-Ortega, Ana-Mar  ıa Fiandor, Mar  ıa-Paz Ruiz, Filomena Trocoli, Rafael D  ıaz-Tejeiro, Carlos Cadenillas, Elena Gonz alez, Virginia Mart  ınez, Margarita L opez-Trascasa, Santiago Quirce, Rafael Selgas, and Teresa Bell  on Hospital La Paz Health Research Institute-IdiPAZ—Research, Madrid Spain Abstract: Several cases of patients with anaphylactic or systemic hypersensitivity reactions to polysulfone (PS) hemodialysis (HD) membranes and tolerance to cellulose triacetate (CTA) membranes have recently been reported. To investigate the mechanisms involved in PS hypersensi- tivity, basophil, T cell, and complement activation were analyzed in acute-phase samples from two patients with systemic reactions to PS-based membranes. Basophil and T cell activation, as well as higher serum tryptase levels were detected in acute-phase samples compared with basal lev- els. Complement levels (C3 and C4) were decreased in acute-phase samples from PS-allergic patients to a higher extent than in samples from control donors taken at the same time points, indicating complement activation during the acute reactions. An experimental external circuit was established on pediatric membranes after rinsing with low or high priming volumes of saline solution, to analyze baso- phils, T cells, and complement activation in blood samples from 10 PS-allergic and 8 nonallergic HD patients upon contact with PS-based or CTA membranes. Predialysis and postdialysis samples were collected. Basophils from PS- allergic patients exhibited increased degranulation, and T cells showed significantly increased activation after contact with PS-based membranes primed with low volumes of saline. No activation was detected in leukocytes from non- allergic patients under the same experimental conditions. Membrane priming with high volumes of saline abrogated activation of basophils and T cells. However, basophils from allergic donors showed significantly higher responses to Fcec stimulation after contact with PS membranes. Basophil degranulation and elevated serum tryptase levels in allergic patients during acute reactions support the sys- temic activation of mast cells and basophils during hyper- sensitivity reactions to PS-based membranes. A leachable component of the membranes might be responsible for cell activation in some patients. Key Words: Hemodialy- sis—Polysulfone membranes—Systemic reactions—Ana- phylaxis—Hypersensitivity. Adverse hypersensitivity reactions during hemo- dialysis (HD) sessions have been reported, with symptoms including malaise, hypotension, dyspnea, nausea or vomiting, and anaphylactic shock (1). Most type I allergic reactions have been reported in patients allergic to sterilizing agents such as eth- ylene oxide (EtO) (2). Hypersensitivity reactions can also occur due to the bioincompatibility of the dialysis membranes; or they can occur in patients on dialysis with AN69 polyacrylonitrile membranes who were simultaneously receiving angiotensin- converting-enzyme inhibitors (ACEi), as a result of the accumulation of bradykinin (3). The incidence of adverse reactions during HD is currently lower with the avoidance of EtO as a dialyzer sterilizing agent, the use of AN69 membranes in patients treated with ACEi, and the increased biocompati- bility of new dialyzers. In recent years, however, a series of cases have been reported in which unex- pected hypersensitivity reactions occurred in patients dialyzed with polysulfone (PS) or doi: 10.1111/aor.12954 Received February 2017; revised March 2017; accepted March 2017. Address correspondence and reprint requests to Teresa Bell on, Hospital La Paz Health Research Institute-IdiPAZ—Research, Paseo de la Castellana 261 Edificio IdiPAZ, 3 a planta, Madrid 28046, Spain. E-mail: teresa.bellon@salud.madrid.org Artificial Organs 2017, 00(00):00–00 Copyright V C 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.