Scleroderma is an autoimmune disease characterised by skin hardening, muscle and joint pain and alterations in various internal organs. In order to correctly treat and monitor patients, a proper diagnosis is necessary, which takes into account symptomatology and the detection of autoantibodies that attack the body's own structures. However, in one group of patients it is not possible to detect any autoantibodies to confirm the diagnosis. A study led by the Translational Immunology and Systemic Diseases groups at Vall d'Hebron Research Institute (VHIR) has discovered, using an innovative technique, a new autoantibody unknown until now that is associated with an increased risk of cancer. The results have been published in the journal Rheumatology.

The study involved 307 patients with scleroderma, who were tested for the presence of autoantibodies in their blood using standard techniques. In 51 of them, no autoantibody was detected. Using a new protocol, implemented by the Vall d'Hebron team, it has been possible to detect a previously unknown autoantibody, called anti-NVL, which is found in 2% of patients and almost 10% of patients in whom no other antibody was initially detected.

The researchers studied the clinical significance of the presence of the anti-NVL autoantibody and found that it was present in a subgroup of patients who often had calcinosis, a build-up of calcium in tissues, and cancer. "This discovery will help to make a more accurate diagnosis of patients with scleroderma. If we know that they have a higher risk of cancer, we can perform a more exhaustive follow-up to detect it early in case it appears", explains Dr. Roger Colobran, head of the Translational Immunology group at VHIR.

From a clinical point of view, "this advance will allow better assessment of patients with scleroderma, because it identifies a unique phenotype characterised by an increased risk of synchronous cancer and by the presence of calcium deposits in the subcutaneous cellular tissue. This facilitates a much more accurate assessment of the different subtypes of scleroderma and the risk of presenting an organic alteration", say Dr. Carmen Pilar Simeón and Dr. Alfredo Guillén, adjuncts of the Internal Medicine Department and the Systemic Autoimmune Diseases area at Vall d'Hebron Hospital and principal investigators of the Systemic Diseases group at VHIR.

Future studies will work to understand the role of NVL, the protein targeted by the newly identified antibodies, in the development of neoplasms. Similarly, although the results suggest that this autoantibody would only be found in patients with scleroderma, it will also be tested in other autoimmune diseases to confirm that it is specific.

An innovative and pioneering technique in Spain to facilitate the detection of antibodies

Traditionally, the detection of new autoantibodies in diseases such as scleroderma and related diseases involves complex laboratory techniques that require the use of radioactive markers. "Our study is based on the use of a protein immunoprecipitation protocol that does not require radioactivity and facilitates the work in the laboratory and, therefore, that other laboratories can implement it and work to advance in the diagnosis of scleroderma", says Janire Perurena, physician of the Immunology Service of the Vall d'Hebron University Hospital and researcher of the Translational Immunology group at VHIR.

In Spain, this protocol, based on a technique that received the Nobel Prize in Chemistry in 2022, is currently only available at Vall d'Hebron, due to the difficulty in setting it up. Currently, it already allows the detection of anti-NVL autoantibodies in patients at Vall d'Hebron and the centre also receives samples from other institutions for analysis.