IMMUNOSENESCENCE AND LATE-ONSET FAMILIAL MEDITERRANEAN FEVER

Abstract

Familial Mediterranean fever (FMF) is an autoinflammatory disease that causes recurrent fever and serositis. FMF often begins in childhood and is diagnosed at an early age. Although it is uncommon for the disease to occur after the age of 40, late-onset patient series have been published and compared to early-onset patient series in recent years. Although it is a genetically inherited disease, the reason why clinical symptoms appear at such a late age in some patients is unknown. The frequency of pathogenic mutations is lower in these patients than in early-onset FMF patients, and the disease has a milder course. Whether or not this clinical presentation is related to immune system changes associated with aging is an open question. Age-related immune system changes, such as an increase in senescence cells, the development of senescence-associated secretory phenotype, and a decline in autophagy with age, can trigger the inflammasome activation. In this regard, understanding the cause of the late-onset of FMF attacks may open up new avenues for research into pathogenesis. In this review, we will first compare the clinical features of the early and late-onset FMF series. We will then consider hypothetical causes of late-onset FMF attacks by reviewing age-related changes in the innate immune system.