The largest study to date on giant cell arteritis identifies four risk profiles

The IPBLN-CSIC identifies genetic markers for this disease that causes inflammation of the blood vessels, the most common after age 50

An international team led by researchers from the López-Neyra Institute of Parasitology and Biomedicine (IPBLN), a center of the Spanish National Research Council (CSIC), has identified for the first time genetic markers associated with the different clinical manifestations of giant cell arteritis (GCA), the inflammation of the blood vessels (vasculitis). more frequent in people over 50 years old, which causes weakening or blockage of blood flow.

The results, published in Annals of the Rheumatic DiseasesThey demonstrate that GCA can be divided into four genetic subgroups with distinct clinical characteristics, an advance that opens the door to more personalized medicine.

Giant cell arteritis causes inflammation of the arteries These are large and medium-sized and can cause serious complications, such as permanent vision loss, stroke, or aneurysms. However, not all patients develop the same symptoms or have the same clinical course, a heterogeneity that until now has hindered both early diagnosis and therapeutic decision-making.

To address this issue, researchers analyzed genetic data from nearly 3,500 patients with giant cell arteritis and more than 15,500 healthy controls from ten countries in Europe and North America.

The study involved hospitals and research centers in ten countries, constituting one of the largest international collaborative efforts to date to investigate the genetic basis of the different clinical manifestations of this disease.

Four genetic profiles with different risks

The analyses identified 14 regions of the genome specifically associated with different forms of disease presentation, seven of which are located in the HLA region, key to the immune response. Furthermore, the study points to candidate genes involved in inflammatory and vascular processes that could explain why some patients develop specific symptoms.

"This work demonstrates that genetics not only influences the risk of developing the disease, but also the way in which it manifests itself in each patient," explains Gonzalo Borrego, predoctoral researcher at IPBLN-CSIC and first author of the study.

One of the most innovative aspects of the work was the application of a statistical model that allowed patients to be classified into four genetic profiles with differentiated clinical characteristics: a group with a predominance of cranial involvementl, another with a mixed pattern, a third with primarily extracranial disease, and a fourth with a high predisposition to suffer serious ischemic complications, such as permanent vision loss.

Early diagnostic

"Identifying this latter group is especially relevant because it could allow us to recognize, from very early stages, the patients at higher risk of developing irreversible complications," he notes. Ana Márquez, senior scientist at IPBLN-CSIC and lead author of the study.

"Although these results still need to be validated in research studies that analyze data over a period of time, also called prospective studies, our data show that genetic information can provide added value to improve the clinical stratification of patients," adds Márquez.

The study results suggest that genetic information could be incorporated into clinical practice in the future to improve patient classification, facilitate more accurate diagnosis, and help identify early on those at higher risk of developing serious complications.

"For years we have known that giant cell arteritis is a very heterogeneous disease, but we were unaware of much of the biological basis that explains this clinical diversity," he points out. Javier Martín, research professor at IPBLN-CSIC and lead co-author of the work.

"This study represents an important step in understanding this heterogeneity and lays the foundation for developing more individualized diagnostic and therapeutic strategies," he concludes.

Source: SINC agency