Autoimmune Response of IgE Antibodies to Cellular Self-Antigens in Systemic Lupus Erythematosus

Abstract

Background: Systemic lupus erythematosus (SLE) patients may exhibit high total IgE and antinuclear IgE antibodies (ANA-IgE). Here, we investigated the specificity of ANA-IgE in SLE patients and the involvement of cytokines in this immune response. Methods: Sera from 92 SLE patients and 68 healthy controls were evaluated for the presence of antinuclear IgE antibodies by immunoperoxidase with HEp-2,000® cells and immunoblotting with IgG-depleted sera. Total IgE, IgE specific to allergens, and serum cytokine levels were determined by ELISA. Results: Antinuclear IgE antibodies were detected only in SLE patients (29/92, 31.5%). High total IgE was associated with ANA-IgE (p < 0.0001), but was not associated with IgE antibodies to allergens. In the immunoblotting, ANA-IgE reacted with nucleosomes (23/29, 79.3%), dsDNA (14/29, 48.3%), SS-A/Ro (14/29, 48.3%), SS-B/La (2/29, 18.7%), Sm (14/29, 48.3%) and RNP (18/29, 62.1%). Patients with ANA-IgE had very low serum IL-4, less IL-5 than controls (p < 0.05), more IL-10 than seronegative patients (p < 0.05), and unaltered IFN-γ levels. The IL-5/IL-10 ratio was lower in ANA-IgE seropositive patients in comparison with either seronegative patients (p < 0.05) or healthy controls (p = 0.001). Controls displayed higher IL-5/IFN-γ ratios than either SLE patients with ANA-IgE (p < 0.05) or patients without these immunoglobulins (p < 0.01). Conclusions: We conclude that IgE antibodies against cell autoantigens involved in protein expression, cellular proliferation, and cell death are present in patients with SLE. Interleukin-10 seems to down-regulate this IgE autoimmune response in SLE.

Basophil Activation-Dependent Autoantibody and Interleukin-17 Production Exacerbate Systemic Lupus Erythematosus

“…Then, we found that IgE, especially autoreactive IgE, mediated basophil activation in SLE, based on the detection of abundant total IgE, autoreactive IgE, and the higher expression of the high-affinity receptor for IgE (FcεRIα) on basophils in patients with SLE, and in vitro experiments including isolated basophils cocultured with the serum of patients with SLE and PEG precipitation CIC (containing IgE). The prevalence of autoreactive IgE in SLE was also observed by others (23, 42, 43). …”

Contribution of autoallergy to the pathogenesis in the NOD mice

“…Although the presence of IgE in different autoimmune disease, including T1D, has been reported [2][3][4][5][6][7]32,33] the potential contribution to the pathogenesis in the different diseases is still to be clarified. In this study, we have explored the role of IgE in a T1D model, i.e.…”

“…The immunoglobulin IgE that is unanimously associated with allergy has also been shown to play a role in autoimmune diseases, a concept referred to as autoallergy [1]. Patients with autoimmune disease such as systemic lupus erythematosus [2,3] that display IgE autoantibodies have poor disease prognosis. Moreover, in several other autoimmune diseases, including rheumatoid arthritis [4], autoimmune thyroiditis [5], bullous pemphigoid [6] and T1D, presence of autoantigen specific IgE has been established [7].…”

Rethinking the Role of Immunoglobulin E and Its High-Affinity Receptor: New Insights into Allergy and Beyond

“…The overall relevance of our initial report [46] describing a role for autoreactive IgE in SLE onset and progression was questioned [48], based on previous studies demonstrating that approximately only 30% of human SLE subjects had detectable levels of autoreactive IgE [49]. This percentage was determined primarily on the detection of dsDNA IgE, which similar to dsDNA IgG showed a highly significant association with disease parameters.…”