Skip to main content

14-04-2022 | Rheumatology | News | Article

Editor's pick

IL-1Ra autoantibodies may contribute to MIS-C pathophysiology

Author: Eleanor McDermid

medwireNews: Autoantibodies against interleukin-1 receptor antagonist (IL-1Ra) are present in a large proportion of patients with multisystem inflammatory syndrome in children (MIS-C), say researchers.

The study, which is published in The Lancet Rheumatology, involved 21 patients with MIS-C aged a median of 7 years who were treated in hospitals in Germany and Spain.

“Although the small number of patients with MIS-C enrolled in this study might pose a limitation, the high numbers of controls (both inflammatory and non-inflammatory) highlight our findings as unique rather than an epiphenomenon,” say Lorenz Thurner (Saarland University, Homburg, Germany) and study co-authors.

The team detected anti-IL-1Ra antibodies in 62% of the MIS-C patients, but in none of 33 children with a suspected growth disorder, 24 with Kawasaki disease, 10 with inactive systemic juvenile idiopathic arthritis (JIA), 146 with mild or asymptomatic COVID-19, or 462 healthy children.

The finding of anti-IL-1Ra antibodies in the MIS-C patients is “in accordance with those in our preprint paper on adults with critical COVID-19, in whom anti-IL-1Ra antibodies were detected in a high proportion of patients (about 50%),” say the researchers.

Antibody titers in the children ranged from 1 in 200 to 1 in 800 and all but one patient had exclusively immunoglobulin (Ig)G antibodies; the other also had IgM antibodies.

The team previously detected progranulin antibodies in a high proportion of adults with critical COVID-19, but these appeared in just one of the MIS-C patients.

In line with the presence of the autoantibodies, plasma levels of free IL-1Ra were significantly lower in patients with autoantibodies than in those without, at an average of 279.4 versus 1746.0 pg/mL. Their levels were also significantly lower than in two tested control groups (Kawasaki disease and JIA) and this remained the case after excluding two MIS-C patients who had received intravenous Ig prior to having blood samples taken.

Of note, the researchers identified a hyperphosphorylated version of IL-1Ra in all the MIS-C patients with autoantibodies but none in those without or in any of the tested controls.

And in two MIS-C patients with follow-up blood samples, “we observed the disappearance of hyperphosphorylated IL-1Ra, which preceded the disappearance of anti-IL-1Ra antibodies,” say Thurner and team.

They conclude: “Collectively, data from both COVID-19 and MIS-C suggest that atypical post-translational modifications are associated with SARS-CoV-2-infection itself or the resulting inflammatory environment, and that these modifications are likely to be immunogenic.”

Writing in a linked commentary, Hamid Bassiri and Scott Canna, both from The Children’s Hospital of Philadelphia in Pennsylvania, USA, say: “These observations are provocative, placing IL-1 signalling downstream of SARS-CoV-2 infection but upstream of hyperinflammation in patients with MIS-C.”

They highlight remaining questions, including what triggers IL-1Ra hyperphosphorylation, why adults with anti-IL-1Ra autoantibodies do not develop MIS-C, and what mechanisms account for MIS-C in patients without these autoantibodies.

The commentators caution that given the limitations of the study – including few longitudinal samples and incomplete mechanistic evaluation – the findings “should neither affect clinical decision making, nor favour an expanded front-line use of anakinra (recombinant IL-1Ra) in patients with MIS-C, particularly given the complete response of most patients to IVIG and glucocorticoids.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

14 April 2022: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.

Lancet Rheumatol 2022; doi:10.1016/S2665-9913(22)00064-9
Lancet Rheumatol 2022; doi:10.1016/S2665-9913(22)00090-X

Related topics

See the research in context now

with trial summaries, expert opinion and congress coverage