Rheumatoid arthritis is an autoimmune disease whose main symptom is joint pain and inflammation. The disease can progressively lead to extremities malformation and severe limitation of movement. An appropriate treatment of this disease which has a worldwide prevalence of 1%, depends on early diagnosis. There are, for instance, many patients infradiagnosed who, in the early stages of the disease, showed poor radiological evidences and, nevertheless, they should have had an aggressive treatment.
Rheumatoid hand in a patient with longstanding disease
One of the best tools for early diagnosis are citrullinated proteins. Citrullination is a chemical transformation suffered by proteins which results in structural changes. This transformation happens in both normal physiological and pathological processes. In the case of rheumatoid arthritis, people affected by this disease lose their tolerance to citrullinated proteins and produce antibodies against them.
This antibodies production starts years before the first symptoms of the disease appear. Therefore, the presence of antibodies is a good marker of the disease. Current commercial tests are based on mutated citrulinated proteins or synthetic citrullinated peptides, which are recognized by the antibodies present in the patient’s serum.
Nevertheless, citrulinated proteins and antibodies developed in patients can be extremely diverse, depending on every patient and the stage of the disease. That often gives a false-negative diagnosis.
New sensors based on synthetic peptides
Scientists at the CSIC’s Instituto de Quimica Avanzada de Catalunya (IQAC) and at the Fundación Clínic have developed ELISA sensors based on synthetic peptides (small proteins) that have, together in a single molecule, regions of several proteins containing the structural changes that happen in rheumatoid arthritis. That’s why they have been called chimeric peptides, after Chimera (the mythological creature formed from parts of various animals). The sensors have as antigens citrullinated domains (or regions) from the fibrin, vimentin and filaggrin proteins.
These ELISA sensors can be especially useful in the case of patients whose symptoms can go unnoticed in early phases of the disease
Isabel Haro, a scientist at the CSIC explains: “Using synthetic peptides instead of proteins mean an advantage for the immunoassay reproducibility. We can have a precise control on the exact epitopes [the changes in the citrullinated proteins]. On the other hand, it is difficult to prepare enough quantity of antigenic proteins with high quality and with high definition in the citrullination. The synthetic peptides, on the contrary, are easily obtained in a pure form and with a well defined structure, and epitopes can be well orientated”.
Trial involving 900 patients
These ELISA sensors can be especially useful in the case of patients whose symptoms can go unnoticed in early phases of the disease. Also, they could be used as a predictive marker of evolution and diagnosis of the disease.
In order to assess how sensitive and specific for the rheumatoid arthritis the new sensors are, scientists have carried out a trial involving 900 patients with several diseases: rheumatoid arthritis, psoriatic arthritis, lupus, chronic C hepatitis and a group of healthy donors. Results shown that the sensors have a specificity of 98% and a sensitivity of 80%. Also, it has been possible to diagnose patients who had negative results with some of the other commercial tests.
Contact:
Isabel Masip (
Instituto de Química Avanzada de
Cataluña
Vicepresidencia Adjunta de
Transferencia del Conocimiento del
CSIC
Tel.: + 34 - 93 400 61 00