IL-1RA Autoantibodies: Insights into Mechanisms and Associated Diseases

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2024 Mar 11

PMID 38463591

Authors

Abdellatif Bouayad

Affiliations

Soon will be listed here.

Abstract

The association of neutralizing autoantibodies targeting interleukin-1 receptor antagonist (IL-1RA) with multisystem inflammatory syndrome, IgG4-related disease, and vaccine-related myocarditis is increasingly recognized. The detection of IL-1RA autoantibodies can be notably affected by the techniques and methods employed. Two categories of assays are available: solid-phase immunoassays, which detect binding of IL-1RA autoantibodies, and functional IL-1 signaling reporter cell assays, which offer greater specificity by determining whether circulating autoantibodies can impede interleukin (IL)-1β signal transduction pathways. It is as yet unclear why only a minority of individuals produce pathogenic anti-IL-1RA autoantibodies in response to coronavirus disease 2019 (COVID19) or vaccination. This review article discusses our current knowledge of the process of IL-1RA autoantibody generation, the underlying pathogenesis, detection, and potential treatment strategies for associated diseases.

References

Whittaker E, Bamford A, Kenny J, Kaforou M, Jones C, Shah P . Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. 2020; 324(3):259-269. PMC: 7281356. DOI: 10.1001/jama.2020.10369. View

Portig I, Sandmoeller A, Kreilinger S, Maisch B . HLA-DQB1* polymorphism and associations with dilated cardiomyopathy, inflammatory dilated cardiomyopathy and myocarditis. Autoimmunity. 2009; 42(1):33-40. DOI: 10.1080/08916930802258651. View

Grass S, Preuss K, Wikowicz A, Terpos E, Ziepert M, Nikolaus D . Hyperphosphorylated paratarg-7: a new molecularly defined risk factor for monoclonal gammopathy of undetermined significance of the IgM type and Waldenstrom macroglobulinemia. Blood. 2011; 117(10):2918-23. DOI: 10.1182/blood-2010-09-306076. View

Ferretti M, Pizarro T, Eisenberg S, Nast C, Cominelli F . Neutralization of endogenous IL-1 receptor antagonist exacerbates and prolongs inflammation in rabbit immune colitis. J Clin Invest. 1994; 94(1):449-53. PMC: 296330. DOI: 10.1172/JCI117345. View

Arase Y, Matsumoto K, Anzai K, Tsuruya K, Sugiyama S, Yoshihara S . Clinicopathological Features of Autoimmune Hepatitis with IgG4-Positive Plasma Cell Infiltration. Dig Dis. 2020; 39(3):225-233. PMC: 8117379. DOI: 10.1159/000510562. View

Piguet P, Vesin C, Grau G, Thompson R . Interleukin 1 receptor antagonist (IL-1ra) prevents or cures pulmonary fibrosis elicited in mice by bleomycin or silica. Cytokine. 1993; 5(1):57-61. DOI: 10.1016/1043-4666(93)90024-y. View

Elkarim R, Dahle C, Mustafa M, Press R, Zou L, Ekerfelt C . Recovery from Guillain-Barré syndrome is associated with increased levels of neutralizing autoantibodies to interferon-gamma. Clin Immunol Immunopathol. 1998; 88(3):241-8. DOI: 10.1006/clin.1998.4573. View

Caruso A, Bonfanti C, Colombrita D, De Francesco M, de Rango C, Foresti I . Natural antibodies to IFN-gamma in man and their increase during viral infection. J Immunol. 1990; 144(2):685-90. View

Furqan M, Chawla S, Majid M, Mazumdar S, Mahalwar G, Harmon E . COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation. Curr Cardiol Rep. 2022; 24(12):2031-2041. PMC: 9703393. DOI: 10.1007/s11886-022-01801-6. View

10.

Della-Torre E, Rigamonti E, Perugino C, Baghai-Sain S, Sun N, Kaneko N . B lymphocytes directly contribute to tissue fibrosis in patients with IgG-related disease. J Allergy Clin Immunol. 2019; 145(3):968-981.e14. PMC: 6960365. DOI: 10.1016/j.jaci.2019.07.004. View

11.

Pfeifer J, Thurner B, Kessel C, Fadle N, Kheiroddin P, Regitz E . Autoantibodies against interleukin-1 receptor antagonist in multisystem inflammatory syndrome in children: a multicentre, retrospective, cohort study. Lancet Rheumatol. 2022; 4(5):e329-e337. PMC: 8963770. DOI: 10.1016/S2665-9913(22)00064-9. View

12.

Woo W, Kim A, Yon D, Lee S, Hwang J, Jacob L . Clinical characteristics and prognostic factors of myocarditis associated with the mRNA COVID-19 vaccine. J Med Virol. 2021; 94(4):1566-1580. PMC: 9015469. DOI: 10.1002/jmv.27501. View

13.

Dinarello C . The IL-1 family and inflammatory diseases. Clin Exp Rheumatol. 2004; 20(5 Suppl 27):S1-13. View

14.

Lanzillotta M, Mancuso G, Della-Torre E . Advances in the diagnosis and management of IgG4 related disease. BMJ. 2020; 369:m1067. DOI: 10.1136/bmj.m1067. View

15.

LaRock D, LaRock C . Assessing Interleukin-1β Activation During Pyroptosis. Methods Mol Biol. 2023; 2641:163-169. DOI: 10.1007/978-1-0716-3040-2_13. View

16.

Hill J, Southwood S, Sette A, Jevnikar A, Bell D, Cairns E . Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. J Immunol. 2003; 171(2):538-41. DOI: 10.4049/jimmunol.171.2.538. View

17.

Boraschi D, Italiani P, Weil S, Martin M . The family of the interleukin-1 receptors. Immunol Rev. 2017; 281(1):197-232. DOI: 10.1111/imr.12606. View

18.

Zhang Q, Pizzorno A, Miorin L, Bastard P, Gervais A, Le Voyer T . Autoantibodies against type I IFNs in patients with critical influenza pneumonia. J Exp Med. 2022; 219(11). PMC: 9485705. DOI: 10.1084/jem.20220514. View

19.

Della-Torre E, Feeney E, Deshpande V, Mattoo H, Mahajan V, Kulikova M . B-cell depletion attenuates serological biomarkers of fibrosis and myofibroblast activation in IgG4-related disease. Ann Rheum Dis. 2014; 74(12):2236-43. PMC: 4806785. DOI: 10.1136/annrheumdis-2014-205799. View

20.

Netea S, Biesbroek G, van Stijn D, IJspeert H, van der Made C, Jansen M . Transient anti-cytokine autoantibodies superimpose the hyperinflammatory response in Kawasaki disease and multisystem inflammatory syndrome in children: a comparative cohort study on correlates of disease. EBioMedicine. 2023; 95:104736. PMC: 10403726. DOI: 10.1016/j.ebiom.2023.104736. View