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.