Rheumatoid arthritis is a debilitaing autoimmune condition which affects million of people. The lack of specific clinical symptoms for patients in the early stage of rheumatoid arthritis (RA) has created strong interest in the laboratory diagnosis of this condition. The main laboratory markers of RA, rheumatoid factor and anti-citrullinated protein antibodies (ACPAs), can be found in patients with other pathologies and in healthy donors. Even today, there is no single laboratory test that can diagnosis RA with high sensitivity and specificity. To improve the diagnosis and treatment of RA, alternative biomarkers including 14-3-3η protein, CTGF growth factor, antibodies against PAD4 or B-RAF, and anti-acetylated and anti-carbamylated protein antibodies have been studied extensively. (Per ulteriori approfondimenti si può consultare l’articolo del sito: “Proteine modificate: i markers diagnostici del futuro”). The simultaneous measurement of a set of biomarkers, is an alternative strategy for the diagnosis of RA and for predicting the therapeutic effect of biological disease-modifying antirheumatic drugs (DMARDs).

Patients with RA are commonly treated with disease-modifying anti-rheumatic drugs (DMARDs) despite the fact that up to 50% of patients are unresponsive to treatment. Up until now, there has been no way to find out whether a patient will effectively respond to treatment. A new study led by researchers at Queen Mary University of London provides potential novel biomarkers for predicting patient responsiveness to disease-modifying anti-rheumatic drugs. The new study, demonstrates that by measuring levels of certain lipid molecules in a patient’s blood that are involved in regulating inflammation, predictions can be made about an individual’s ability to respond to these drugs. These mediators are called resolvins and derive from enzymatic processing of some omega-3 fatty acids. The common root enzyme of the process is cyclo-oxygenase 2 (COX-2), which is inihibited by NSAIDs like ibuprofen or diclofenac. But if the substrate is arachidonic acid, the enzyme produces prostaglandins which are inflammatory. If the substrate is, instead, an omega-3 acid the end-product is and anti-inflammatory lipid just like the resolvins.

Professor Jesmond Dalli, lead Author, explained: “Currently a large proportion of patients with RA are unresponsive to DMARDs and are therefore unnecessarily exposed to their side effects. In addition, it can currently take up to six months from treatment initiation to determine whether someone will or will not respond to these medicines. For the patients who do not respond to the treatment, the disease gets worse before they are able to find a treatment that is more likely to work for them. The research was conducted using blood from healthy RA patients who were both responsive and unresponsive to treatment. The blood was collected before treatment initiation or six months after treatment commenced. We then measured the levels of protective molecules using mass spectrometry-based assays that were coupled with artificial intelligence methodologies to identify molecules that can predict responses to treatment. We are planning now to conduct a larger study to evaluate if these initial findings can be applied to a bigger patient group”.

• Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Gomez EA et al. Nature Commun 2020 Oct 27; 11(1):5420. 

Ramírez J et al. Rheumatology (Oxford) 2020 Jul 12:keaa258.

Takahashi S et al. Rheumatology (Oxford) 2019; 58(12):2153. 

Boeters DM et al. Ann Rheum Dis. 2019; 78(11):1497-1504.