12 / 2025
A study by the Paul-Ehrlich-Institut shows that the seasons have an influence on the response of certain immune cells. In comparison to other seasons, immune cells from healthy blood donors reacted particularly strongly in the spring to a combination of coagulation factor VIII and a bacterial danger signal. The understanding of this seasonal variation could help in planning and adapting the treatment of haemophilia A to reduce the risk of inhibitor formation. Research and Practice in Thrombosis and Haemostasis reports on the research in its online edition dated 17 November 2025.
Source: Paul-Ehrlich-Institut
Our research shows that a person's immune cells don't respond the same way in every season. For the first time, we are seeing clear seasonal patterns that could be relevant to patient care, such as in the treatment of haemophilia A patients with factor VIII coagulation factors.
Professor Zoe Waibler (Vice President (acting) of the Paul-Ehrlich-Institut)
The bleeding disorder haemophilia A is a rare hereditary blood clotting disorder. Affected patients produce too little or a defective version of coagulation factor VIII, which is indispensable for haemostasis. Without treatment, patients can experience dangerous, long-lasting bleeding episodes. Standard therapy consists of the administration of factor VIII preparations obtained from blood plasma (plasma-derived) or produced by genetic engineering (recombinant) in order to replace the low factor levels.
However, a major challenge associated with such therapy is the formation of antibodies (also called "inhibitors"). Inhibitors recognise the supplemented factor VIII and block its effects. Around 25 to 35 percent of patients with severe haemophilia A develop such inhibitors – often triggered by certain situations in which the immune system is on particularly high alert, such as in the time period following operations, infections, or vaccinations.
Source: karyna_345/Shutterstock
The present study was conducted by a team of researchers at the Paul-Ehrlich-Institut headed by Professor Zoe Waibler, Acting Vice President of the Paul-Ehrlich-Institut, and Dr Martina Anzaghe, Research Immunology Section at the Paul-Ehrlich-Institut. The researchers analysed blood donations from healthy individuals between 2012 and 2023. Over 400 blood samples were analysed. The team investigated how strong the reaction of certain immune cells was to the combination of factor VIII preparations and a bacterial danger signal (lipopolysaccharide, LPS) and which factors may influence this reaction.
The surprising result: the strength of the immune response was not affected by the donor's sex or the factor VIII preparation used. There were also no individual differences between donors that had an effect. Instead, the time point of the blood donation was crucial – and clearly correlated with the seasons.
The dendritic cells (immune cells) showed an especially strong response in spring. This was due to a lower baseline level of the CD86 surface molecule, which is extremely important for communication between immune cells. CD86 levels varied depending on the season and the expression level correlated with dendritic cell activation and the release of pro-inflammatory messenger substances (cytokines) such as TNF-α. T helper cell activity was also partially affected.
The researchers suspect that factors such as sunlight, vitamin D levels, seasonal infections, and pollen exposure affect the immune response against FVIII. It is well known that vitamin D levels are high in the summer and low in the winter and spring – which may suppress or promote certain immune reactions.
The results show that the formation of antibodies against factor VIII preparations is a complex process that is influenced by many factors. The time of year also apparently plays a role, as immune cells can be activated to different degrees depending on the season. Such differences could help in planning and adapting treatment for haemophilia A patients to reduce the risk of antibody formation. Understanding the influence of Vitamin D levels and certain immune cell markers could contribute in the future to making treatment more individualised and effective.
Updated: 10.12.2025
