The anti‐FcεRI antibody MAR‐1 depletes basophils and cross‐reacts with myeloid cells through its Fc portion

William Worrall (1) , Jasper Kamphuis (1) , Julien Stackowicz (2, 3) , Aurélie Mougel (1) , Emilie Mauré (1) , Cyprien Pecalvel (1) , Sébastien Brûlé (4) , Pierre Bruhns (2) , Laurent Guilleminault (1, 5) , Laurent Reber (1)

1 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
2 Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology
3 SU - Sorbonne Université
4 Biophysique Moléculaire (plateforme) - Molecular Biophysics (platform)
5 Service Pneumologie-Allergologie [CHU Toulouse]

In humans, the high-affinity IgE receptor FcεRI is expressed as a tetramer in mast cells (MCs) and basophils, and as a trimer in additional myeloid cell populations, including monocytes, macrophages, dendritic cells (DCs), and Langerhans cells.1 In mice, the expression profile of FcεRI is more debatable. Some studies report FcεRI+ macrophages and DCs.2 However, recent data indicate that the anti-FcεRI mAb (clone MAR-1) used in all these studies can recognize myeloid cells in an FcεRI-independent manner, and cross-reacts with FcγRI and FcγRIV.3, 4 Since MAR-1 has been extensively used in vivo to assess the role of FcεRI and to deplete basophils,5 the off-target effects of this mAb raise concerns regarding some of the conclusions made in prior studies. We thus decided to assess by which mechanism MAR-1 cross-reacts with FcγRs, and whether this cross-reactivity accounts for some of the functions previously attributed to FcεRI and/or basophils.

Mots clés: anaphylaxis; basophil; IgE; mast cells

Domaines: Médecine humaine et pathologie

William Worrall, Jasper Kamphuis, Julien Stackowicz, Aurélie Mougel, Emilie Mauré, et al.. The anti‐FcεRI antibody MAR‐1 depletes basophils and cross‐reacts with myeloid cells through its Fc portion. Allergy, 2022, 77 (6), pp.1903-1906. ⟨10.1111/all.15269⟩. ⟨hal-03987932⟩