The congenital disease favism causes sickness and even jaundice in patients after they consume beans. The culprit is a particular enzyme deficiency, which destroys the red blood cells. Scientists from the University Children’s Hospital Zurich have now discovered that, in the event of a severe or complete enzyme deficiency, patients can also suffer from an immunodeficiency. Patients need to be treated differently depending on the severity of their deficiency.
Favism is a common hereditary disease, affecting around 400 million people worldwide. It is caused by a lack of the enzyme glucose-6-phosphate dehydrogenase (G6PD). This deficiency triggers the destruction of red blood cells (hemolysis) and anemia in patients after they consume fava beans and certain drugs.
In the case of severe forms with a complete enzyme deficiency, life-threatening infections with bacteria and fungi can even occur. However, most specialists who treat these patients are unaware of this. Scientists from the Children’s Research Center at the University Children’s Hospital Zurich and the University of Zurich now reveal the mechanistic link between severe G6PD deficiency and immunodeficiency.
A functioning G6PD enzyme plays a key role in the so-called pentose phosphate pathway in cell metabolism. The co-factor nicotinamide adenine dinucleotide (NADPH) is formed in this process, which has two functions: On the one hand, it guarantees that sufficient glutathione is available in the red blood cells, which protects these cells as an antioxidant.
In the event of a G6PD deficiency, the cells lose this protection against oxidative stress, which results in hemolysis. On the other hand, the co-factor NADPH allows the formation of reactive oxygen compounds in the immune system’s phagocytes that they need to fend off bacterial and fungal infections.
Immunodeficiency similar to septic granulomatosis
The Zurich scientists teamed up with research colleagues from Germany to clarify the mechanism of the defective immune defense in G6PD patients: “In the event of a complete G6PD deficiency, i.e. without any demonstrable residual function of the enzyme, the phagocytes are unable to form any reactive oxygen compounds such as hydrogen peroxide due to the deficient provision of NADPH,” explains Janine Reichenbach, a professor of pediatric immunology at the University of Zurich.
As with a known immunodeficiency in phagocytes called chronic granulomatous disease (CGD), this causes a defective formation of DNA networks – so-called “neutrophil extracellular traps” (NETs), which are needed to capture and kill off bacteria and fungi. “Besides the more minor G6PD deficiency, which chiefly affects red blood cells, a severe or complete enzyme deficiency therefore also constitutes an immunodeficiency in the phagocytes,” says Reichenbach, summarizing the results of the study.
Impact on therapy
This has consequences for the treatment of patients with a G6PD deficiency: “In order to determine the need for permanent antimicrobial prophylactic measures, the severity of the G6PD deficiency has to be determined first during the diagnosis. In the event of a severe enzyme deficiency, the formation of reactive oxygen compounds and DNA networks ought then to be analyzed,” concludes Reichenbach.
Ulrich Siler, Susana Romao, Emilio Tejera, Oleksandr Pastukhov, Elena Kuzmenko, Rocio G. Valencia, Virginia Meda Spaccamela, Bernd H. Belohradsky, Oliver Speer, Markus Schmugge, Elisabeth Kohne, Manfred Hoenig, Joachim Freihorst, Ansgar S. Schulz, Janine Reichenbach, Severe G6PD-deficiency leads to susceptibility to infection and absent NETosis, Allergy and Clinical Immunology, July 22, 2016. DOI: 10.1016/j.jaci.2016.04.041
The University Children’s Hospital Zurich conducts an average of one to two favism analyses per day. One person with favism is usually identified every month.
Favism primarily affects the Mediterranean region, Africa, the Middle East and some Asian countries such as Thailand or India. Its prevalence in Switzerland is less than 0.5 percent (see S. Hofmann et al.; Swiss Medical Forum 2016). Due to migration and travel behavior, however, the number of favism cases in Switzerland could rise in future.
Prof. Dr. med. Janine Reichenbach
Dr. Ulrich Siler
University Children’s Hospital Zurich
Phone: +41 44 635 29 10
University of Zurich
Phone: +41 44 634 44 67
Nathalie Huber | Universität Zürich
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy