Family Mediterranean fever is an autoinflammatory syndrome, transmitted in an autosomal recessive pattern affecting mostly the mediterranean belt. The prevalence has been discovered mostly in the Jews, Arabs, Turkish and Armenian Population. It is characterized by recurrent bouts of Arthritis, Serositis, Abdominal pain, Erysipelas like erythema and if untreated can lead to Secondary Renal Amyloidosis leading to early mortality.  

The discovery of MEFV Gene, which induces activation of a protein called Pyrin which in turn activates IL1 B is responsible for producing inflammation in the system. 

Over centuries, a biological arms race has been fought between humans and microbial pathogens. Microbes affect the human genome in many ways. They can influence genomic variations that gradually accumulate in the human population over time. And one such mutation has been found with Yersinia Pestis. Just like Sickle Cell trait confers protection against Malaria, it was suspected that mutant Pyrin may help the FMF patients in survival. 

Did you know? The 2 plague epidemics caused by Yersinia Pestis (AD: 541-750, The Plague of Justinian) and the Black Death (AD 1331-1855) affected Mediterranean belt the most, almost reducing the population by 50 %. The Black death is by far the most dreaded non-viral epidemic so far which reduced the world population by 50 %. 

The discover of YopM, Virulence factor secreted by Y. Pestis specifically inhibits the pyrin inflammasome in contrary to the other bacteria which lack this virulence factor. That is where the linkage was sought. The data was analysed on 4163 Turkish people harbouring the gene. After the in vitro studies, it was discovered Y. pestis increases 14-3-3 binding to pyrin, and counters the effect of C3 toxin to decrease 14-3-3 binding. Y. pestis-infected human CD14+ monocytes, the binding of YopM to endogenous pyrin and resulting pyrin phosphorylation was diminished in the cells from FMF patients with homozygous or compound heterozygous domain mutations relative to healthy controls. Taken together with the reduced binding of PKN to disease-associated mutant pyrin, the decreased binding of human pyrin to YopM provides them with resistance against the infection.

Although there are numerous other microbial pathogens that affect the activity of the pyrin inflammasome, taking the population genetics, historical record, and biology of pyrin and YopM into account, it is likely that Y. pestis exerted evolutionarily selective pressure for FMF-associated pyrin variants in the Middle East and Mediterranean basin.