The CD5 Molecule Helps to Combat Septic Shock Caused by Fungi

Septic shock is a serious medical condition caused by an infection that spreads in an uncontrolled manner throughout the body via the circulatory system. It produces severe inflammatory symptoms with cardiovascular failure caused by particularly virulent bacterial or fungal toxins in the blood. It is the main cause of death in intensive care units, with a mortality rate of between 30% and 50% of patients who suffer from it.

This is because, once septic shock is detected, standard antibiotic therapy and other support measures are insufficient to correct the physiopathologic changes associated with septic shock. The team, led by Dr. Francisco Lozano, a senior consultant at the Immunology Department of Hospital Clínic and leader of the IDIBAPS team on Immunoreceptors of the Innate and Adaptive Immune System, published a study in the journal Proceedings of the National Academy of Sciences (PNAS) in which they describe the efficacy of the CD5 protein against septic shock caused by fungi. Dr. Jorge Vera and Dr. Rafael Fenutria are the main authors of the study, in which members of Hospital del Mar, Barcelona, the Universidad Complutense, Madrid and East Tennessee State University (US) also took part. This study, together with previous complementary research by the team could become the first effective response to fungal and bacterial septic shock. The possible therapeutic applications have been patented and the aim is to transfer them to clinical practice.

CD5 is a receptor found in the membrane of certain cells of the immune system (lymphocytes, macrophages, dendritic cells). It is known for its function in modulating lymphocyte activation and differentiation signals. This protein has the ability to detect polysaccharides from fungal cell membranes and bind to them, helping to trigger a protective immune response. The IDIBAPS researchers used molecular biology techniques to produce sufficient quantity of a soluble form of this protein to carry out experiments in mice in which fungal septic shock had been induced. In vivo studies have shown that pre-treatment with injected CD5 increases survival; this was also observed when the protein was administered a few hours after induction of shock. Furthermore, a protective effect was shown against the inflammatory response triggered by the infection - one of the main causes of mortality. Unlike CD5, conventional antibiotic treatments do not eliminate the toxins that cause the inflammation. Soluble CD5, as well as binding to the fungi and their toxins, forms aggregates that prevent the dissemination of the pathogens and facilitate their elimination by the phagocytes. It also interferes with lymphocyte activation and reduces the inflammatory component resulting from this phenomenon.

In prior studies, the IDIBAPS team, led by Dr. Francisco Lozano, discovered similar properties of the CD6 molecule, applicable to septic shock due to bacteria. Thus, CD5 and CD6 are complementary and could lead to a new combined biological treatment to combat septic shock due to multiple microbes or in which the agent has not yet been identified. This would be a possible broad-spectrum treatment that would not cause any adverse reaction by the immune system, as the proteins used are part of our cells. The application of these proteins has been patented through the AVCRI and the Fundació Clínic per a la Recerca Biomèdica and further studies are required to find a way to apply their properties to humans.