Anti–IL-1 receptor antagonist autoantibodies stimulate inflammatory and fibrotic mediators in IgG4-related disease

A new study published in the journal of allergy and clinical immunology has reported that anti-interleukin-1 receptor antagonist (IL-1RA) autoantibodies in patients with IgG4-RD can induce e pro-inflammatory and profibrotic meditator production through neutralizing of anti–IL-1 receptor antagonist (IL-1RA) autoantibodies.

Jarrell and co-researchers carried out the sequencing of plasmablast antibodies in IgG4-RD patients and characterized their specificities using cytokine microarrays. In vitro assays were performed to evaluate the role of anti-IL-1Ra autoantibodies in IgG4-RD patients. Clonally expanded plasmablast-derived mAb obtained from a patient with IgG4-RD demonstrated robust sensitivity against human IL-1RA. An increased level of reactivity against IL-1RA and neutralizing IL-1RA activity was observed in patients with IgG4-RD as opposed to plasma of the controls, this indicated the in vitro production of inflammatory and fibrotic mediators. The researchers also identified IL-1RA in lesioned tissues obtained from IgG4-RD patients. The study also noted that a greater number of organs were affected in patients with IgG4 subclass anti-IL-1RA autoantibodies compared to patients without anti-IL-1RA autoantibodies. Peptide analyses showed that anti-IL-1RA antibodies targeted IL-1RA epitopes sites near the IL-1RA/IL-1R interface. There was an increased level of anti-IL-1RA autoantibodies in serum obtained from SLE and RA patients than those in the controls.

The present study provided novel evidence on the identification of anti– IL-1RA autoantibodies that exhibit antagonizing inhibitory effects of IL-1RA in IgG4-RD patients thereby promoting proinflammatory and profibrotic mediators production. These findings help in further exploring the underlying immunologic mechanism beneath the pathogenesis of IgG4-RD. The presence of these autoantibodies in SLE and RA patients further indicates a strong common pathway in multiple autoimmune diseases. Further validation of the current study can help in determining diagnostic, prognostic, and pathogenic prospectives of anti–IL1RA autoantibodies in IgG4-RD.

Reference: Jarrell JA, Baker MC, Perugino CA, Liu H, Bloom MS, Maehara T, Wong HH, Lanz TV, Adamska JZ, Kongpachith S, Sokolove J, Stone JH, Pillai SS, Robinson WH. Neutralizing anti-IL-1 receptor antagonist autoantibodies induce inflammatory and fibrotic mediators in IgG4-related disease. J Allergy Clin Immunol. 2022 Jan;149(1):358-368.