There are large individual differences in susceptibility to respiratory infections, such as acute ear, nose and throat infections caused by viruses. These diseases are a major cause of morbidity and absenteeism, with coronary pandemic being a recent example.
The body's defence system constantly encounters pathogens on the surfaces of the upper respiratory tract - the nasal cavity, mouth and throat - which it should identify and destroy to avoid becoming ill. The factors influencing the effectiveness of this defence mechanism are not fully understood. However, previous studies have suggested that hereditary factors play a role in individual susceptibility to disease.
A large-scale genetic study carried out in collaboration between researchers from the University of Helsinki, HUS Helsinki University Hospital and the Broad Institute confirms this finding and significantly increases our understanding of the genetic risk factors that influence susceptibility to upper respiratory tract infections.
Using data from the FinnGen study, which covers more than 260,000 participants, the research team was able to identify more than 40 genetic regions that predispose to upper respiratory tract infections, 14 of which were previously unknown. In particular, genes associated with so-called type 2 inflammation were highlighted in the results. This finding was confirmed using data from the UK biobank.
“Highlighting genes associated with type 2 inflammation is an important finding because biological therapies have been developed for this inflammatory pathway. Type 2 inflammation is associated with high levels of eosinophilic white blood cells and occurs in some subtypes of asthma and in almost all long-term sinusitis in Western countries”, said Sanna Toppila-Salmi, an ear, nose and throat specialist at HUS, who was responsible for the clinical part of the study.
Inflammatory diseases share common predisposing factors
Next, the researchers wanted to find out whether the identified genetic risk factors predispose to many different inflammatory diseases or whether they are mainly associated with only one specific disease.
The results showed that seemingly completely different disease states, such as tonsillitis and dental infections or nasal polyps and asthma, had a surprising number of common genetic factors.
“It was particularly interesting to note the extent to which shared genetic susceptibility was also seen with inflammation outside the upper respiratory tract. For example, genetic variation in susceptibility to recurrent pharyngitis was also clearly correlated with acute inflammatory bowel conditions and ear infections”, says Elmo Saarentaus, a postdoctoral researcher at the Institute for Molecular Medicine Finland (FIMM) at the University of Helsinki, who conducted the study.
Unravelling the mechanism of shared genetic susceptibility may help to identify common factors between otherwise seemingly different disease states. Similar findings have previously demonstrated similarities between inflammatory bowel diseases, for example, and between schizophrenia and bipolar disorder.
“Although the ultimate mechanisms and environmental risk factors for these diseases may be quite different, hereditary susceptibility may be partly superimposed. Thus, common mechanisms can be identified - such as now in type 2 inflammation - for which targeted therapies can potentially benefit several disease groups", Elmo Saarentaus continues.
The results also allowed to distinguish gene variants specific to different disease states. In recurrent pharyngitis, in particular, different forms of genes important for TNF receptor 2 activation were found to be important, highlighting the importance of the immune system in pharyngitis.
These results may have implications for future patient management. In particular, many common predisposing factors were found in the background of nasopharyngeal and sinus diseases and asthma, which can be applied to the development of new therapies, prognosis assessment and the design of targeted treatments.
The results of the study were published in Nature Communications.
Original publication: Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation. Saarentaus E., Karjalainen J., Rämö J. et al. Nature Communications (2023), DOI:10.1038/s41467-022-33626-w