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.

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