Recurrent pericarditis: new perspectives from the PERIPLO study

A new international study has identified a potential immune marker that could help explain and track inflammation in idiopathic recurrent pericarditis (RP), a rare and often difficult-to-treat condition causing repeated inflammation of the heart lining.

The PERIPLO study, involving 142 patients across 9 referral centers, found that more than half of patients with active recurrent pericarditis carried neutralizing autoantibodies against one of the body’s own natural anti-inflammatory mediators, the interleukin-1 receptor antagonist (IL-1Ra). These autoantibodies were absent in patients whose disease was in remission. In patients with active disease, these autoantibodies bind to IL-1Ra and literally take this anti-inflammatory mediator out of the game. 

“Recurrent pericarditis is a painful and sometimes debilitating condition. Our findings suggest that, during active phases of the disease, the body may produce temporary antibodies that block its own natural defenses against a key inflammatory pathway,” said Maddalena Alessandra Wu (University of Milan), Principal Investigator of the PERIPLO study.

Unlike other autoimmune markers and antibodies sometimes seen in RP, the identified anti-IL-1Ra autoantibodies appear to represent a distinct immune pathway, specifically tied to IL-1 signaling – a well-known driver of pericarditis.

“While some of the present results match our earlier observations in different context, we were struck by the extremely tight association of anti-IL-1Ra antibodies and active RP. In fact, all of the 25 patients identified as seropositive in this study presented with active disease when blood for our analysis was drawn,” highlights  Lorenz Thurner (Saarland University, Homburg, Germany), who spear-heads the discovery of these new autoantibodies.

The fact that anti-IL-1Ra antibodies were found in more than half (53%) of RP patients with active disease is also reflected by a strong link of autoantibody presence and elevated levels of key inflammatory markers circulating in patients’ blood.

“On molecular marker level, we have not seen such close association of inflammation and anti-IL-1Ra antibodies in several of our previous studies,” Christoph Kessel (University Hospital Münster, Germany) adds. “In these lines our present findings in the context of RP really stand out”.

Importantly, within the PERIPLO study, the investigators also had the opportunity to follow some patients over time, tracking both clinical disease activity and antibody status. 

Here, they observed that the antibodies disappeared when inflammation resolved, while the patients’ anti-inflammatory defense mechanisms recovered. This suggests that anti-IL-1Ra antibodies appear only temporarily and link to active disease flares.

“Importantly, in these individual follow-up data, but also the entire study results we observed no link between antibody development and treatment with anakinra, a drug that mimics IL-1Ra,” points out Antonio Brucato,  Director of the referral Center for pericardial diseases (University of Milan). “This is reassuring in terms of applying anakinra as a treatment of choice in RP”.

Overall, these new findings highlight a complex interplay between inflammation and autoimmunity in RP and can improve understanding of why some patients relapse while others achieve remission.

While the findings are promising, the researchers emphasize that more studies are needed, particularly with larger long-term patient samples, to confirm the role of IL-1Ra antibodies in disease progression and relapse.