An international consortium led by specialists from the Institute of Parasitology and Biomedicine López-Neyra (IPBLN), a center of the Higher Council for Scientific Research (CSIC), has for the first time managed to identify genetic markers linked to the various clinical manifestations of giant cell arteritis (GCA). This is the most common vasculitis in individuals over 50 years old, characterized by the inflammation of large and medium-caliber blood vessels that can weaken or obstruct blood flow.
The findings, published in the journal "Annals of the Rheumatic Diseases," reveal that GCA can be grouped into four well-differentiated genetic subtypes from a clinical point of view, which represents a decisive step towards more personalized care for these patients.
This pathology can trigger severe complications, including irreversible vision loss, stroke, or aneurysms. However, the evolution and symptoms differ significantly among patients, a clinical variability that until now complicated both early diagnosis and the choice of the most appropriate treatment.
To delve into these differences, the team analyzed genetic information from nearly 3,500 people with giant cell arteritis and more than 15,500 healthy individuals as a control group, from ten European and North American countries. The work has involved hospitals and reference centers from those ten countries, forming one of the largest international projects dedicated to unraveling the genetic basis of the different forms of presentation of the disease.
Four genetic profiles with differentiated risks
The analysis allowed the detection of 14 regions of the genome specifically related to different clinical patterns of GCA, of which seven are located in the HLA region, fundamental for the immune system's response. The study also identifies candidate genes involved in inflammatory and vascular mechanisms that could clarify why certain patients develop specific symptoms while others do not.
"This work demonstrates that genetics not only influences the risk of developing the disease but also the way it manifests in each patient," explained Gonzalo Borrego, predoctoral researcher at IPBLN-CSIC and the first author of the article.
One of the most notable elements of the research has been the use of a statistical model that allowed grouping patients into four genetic profiles with well-defined clinical traits: one group with primarily cranial involvement, another with a mixed pattern, a third with predominantly extracranial disease, and a fourth with a marked predisposition to suffer severe ischemic complications, such as permanent vision loss.
Towards a more early and precise diagnosis
"The identification of this last group is especially relevant because it could allow recognizing from very early stages the patients at greater risk of developing irreversible complications," points out Ana Márquez, senior scientist at IPBLN-CSIC and principal author of the study.
"Although it will still be necessary to validate these results in research studies where data is analyzed over a period of time, also called prospective studies, our data shows that genetic information can provide added value to improve the clinical stratification of patients," adds Márquez.
The authors propose that, in the future, this genetic data could be incorporated into clinical practice to refine the classification of patients, facilitate more accurate diagnoses, and detect as soon as possible those who present a high risk of severe complications.
"For years we have known that giant cell arteritis is a very heterogeneous disease, but we were unaware of much of the biological bases that explain that clinical diversity," highlights Javier Martín, research professor at IPBLN-CSIC and principal co-author of the work.
"This study represents an important step towards understanding that heterogeneity and lays the groundwork for developing more individualized diagnostic and therapeutic strategies," concluded Martín.