Systemic lupus erythematosus
The tolerability of OMZ was evaluated in a phase Ib clinical trial in patients with SLE with increased levels of anti-dsDNA, anti-Sm and/or anti-SSA IgE AAb measured by ELISA assay and moderately active non-renal, non-CNS lupus170. SLE Disease Activity Index 2000 (SLEDAI 2K) scores but not in other measures of clinical activity improved in the OMZ group. Also, the SLE Responder Index and the absolute change in the SLEDAI 2K score were low when compared to other larger clinical trials. However, there was no worsening in other scores, and OMZ treatment showed a trend towards reduction in IFN gene signature, especially in subjects with high baseline IFN signature. Importantly, IgE AAb in SLE facilitate TLR9-mediated pDC activation and IFNα production23. OMZ and LGZ have both been shown to remove IgE from pDC surface and to restore TLR9 and T regulatory cells homeostasis171,172. The IgE-dependent basophil-mediated AAb production amplification in SLE also supports targeting IgE in this disease32. Hence, it will be of primary interest to confirm the therapeutic value of the anti-IgE approach for SLE in clinical trials with larger patient populations.
Patients affected by the AbAID discussed in the present review may putatively benefit from IgE-targeting therapies based on the prevalence of the identified autoreactive IgE and the FcεRI-bearing cells known to be involved in their pathophysiology. Further investigations will be required at both pathophysiological and clinical levels to validate the therapeutic values of targeting IgE and autoreactive IgE in these conditions.