ACTIVATED SENESCENCE PATHWAYS IN THE TEMPORAL ARTERIES OF PATIENTS WITH GIANT CELL ARTERITIS
Authors: W.E Jiemy et al.
As the incidence for Giant Cell Arteritis (GCA) increases with advanced age, immune-senescence is likely to be an important pathogenic factor. Inhibition of IL-6 and of GM-CSF have been shown to control disease and both molecules are senescence-associated secretory phenotype (SASP) cytokines.
Immunohistochemical stainings of the SAPS cytokines IL-6 and GM-CSF as well as the senescence markers p21 WAF1/CIP1 and p16/INK4A were performed on temporal artery biopsies (TABs; n=8) from patients with GCA and from age-matched controls (n=14). Stainings were scored quantitatively by using QuPath software.
All four markers were detected in the inflamed GCA temporal arteries, most notably by giant cells surrounding the intimal lamina elastica. The expression of all four markers were significantly lower in control arteries. Cells positive for p21 WAF1/CIP1 and p16/INK4A that co-express IL-6 and GM-CSF were detected throughout the vessels.
The data show the presence of activated senescence pathways at the site of vascular inflammation in GCA. They help to explain the age-associated increase in the incidence of GCA and they also give a rational for the therapeutic efficacy of IL-6 and GM-CSF blockade.