Several Protein Biomarkers Could Protect Against Disease Development

Inflammatory processes are associated with a large range of human diseases, including rheumatic diseases and allergies. Protein biomarkers are measurable molecules that can have a prognostic value in patients, be used to diagnose disease, or indicate severity of disease. 

However, the causal relationship between a protein biomarker and inflammatory diseases is generally unknown.

The protein could either be expressed in response to the disease, to protect from tissue damage, or the high expression of the protein could be the underlying factor behind the development of disease.

In the current study, the scientists used a method called Mendelian Randomisation to identify protein biomarkers that have a direct causal effect on protecting or promoting disease development.

“In Mendelian Randomisation we use genetic information to determine whether individuals born with high natural levels of a protein will have a higher or a lower risk of developing a disease. Mendelian Randomisation has often been called nature’s own clinical trial since individuals are randomized at birth to receive genetic variants that might increase the protein biomarker levels,” says Torgny Karlsson one of the leading researchers behind the study.

The study showed that IL-12B protects against psoriasis and psoriatic arthropathy, LAP-TGF-b-1 against osteoarthritis, TWEAK against asthma, VEGF-A against ulcerative colitis, and LT-a against both type 1 diabetes and rheumatoid arthritis.

Only one biomarker was found to have a damaging effect, namely IL-18R1, which increased the risk of developing allergy, hay fever and eczema.

“Surprisingly, we found that a larger fraction of the proteins investigated actually protect against disease development, rather than increasing the risk of disease,” says Weronica Ek one of the leading researchers behind the study.

The protective effects identified are important, since they can shed light on the pathogenesis of inflammatory disease.

However, many of these proteins may serve, or are already being investigated, as potential drug targets.


Weronica E. Ek, Torgny Karlsson, Julia Höglund, Mathias Rask-Andersen, Åsa Johansson. Causal effects of inflammatory protein biomarkers on inflammatory diseases. Science Advances, 2021; 7 (50) DOI: 10.1126/sciadv.abl4359

Uppsala University. “Several protein biomarkers protect against disease development.” ScienceDaily. ScienceDaily, 8 December 2021. <>.

Materials provided by Uppsala University. Original written by Linda Koffmar. Note: Content may be edited for style and length.

Images from:

Photo by Edwatd Jenner