Clonal differences in IgE antibodies affect cutaneous anaphylaxis-associated thermal sensitivity in mice

Abstract

Cellular and molecular mediators of immune responses are increasingly implicated in acute and chronic pain pathophysiologies. Here we demonstrate that passive cutaneous IgE/Ag anaphylaxis provokes increased thermal sensitivity in the hind paw tissue of mice. The murine anti-DNP IgE antibodies SPE-7 and ε26 are known to induce differential cytokine production in bone marrow cultured mast cells in vitro without antigen challenge. We found a novel, antigen-dependent heterogeneity in the thermal pain responses elicited in the hind paws between SPE-7 and ε26 sensitized DNP-challenged mice. Mice experienced pronounced hind paw thermal sensitivity lasting 6 hours after DNP challenge when sensitized with SPE-7 but not ε26 IgE. The two IgE clones induced equivalent hind paw edema, neutrophil influx, cytokine production, and reduction in tissue histamine content in vivo, and bound to the same or overlapping epitopes on the DNP antigen in vitro. Therefore IgE antibodies against the same antigen can induce comparable inflammation, yet contribute to markedly different anaphylaxis-associated pain within an allergic response, suggesting that non-canonical IgE binding partners such as sensory neurons may play a role in allergy-related pain responses.

Tetrahydrocannabinol Reduces Hapten-Driven Mast Cell Accumulation and Persistent Tactile Sensitivity in Mouse Model of Allergen-Provoked Localized Vulvodynia

“…The contributions of mast cells to pain pathologies have been well studied in recent years [18]. These “tunable” effectors of tissue pathology [19] are now known to contribute to protective painful responses to noxious stimuli [20,21] as well as to acute and chronic pain conditions such as migraines [22], sickle cell pain [23], irritable bowel disorders [24] and pain associated with neuropathic and neurological diseases [25,26]. Mast cell increases in vulvar biopsy samples from vulvodynia patients were first reported over a decade ago [3,27] but are not ubiquitous in all patients [28].…”

Profiling of how nociceptor neurons detect danger – new and old foes

“…The IgG receptors, FcyRs, were found to be present on human peripheral neurons as early as in foetus aged from 20 to 38 weeks , supporting a role for IgG‐FcyR in CNS development. Recent studies also reported an implication of neuronal‐Ig system in Alzheimer's disease , chronic pain , allergy and antigen‐specific autoimmune diseases . Overall, Ig sensory neuron crosstalk may serve a role in pathophysiology and, therefore, deserves closer scrutiny.…”

“…In line with this, functionally active FcγRI and FcεRI were expressed on rodents’ superior cervical ganglion neurons and myenteric plexus neurons . Moreover, in a mouse model of cutaneous anaphylaxis; IgE‐IC drives thermal sensitivity and severe pain . IgE was also implicated in the pathogenesis of food allergy, where allergic mice showed an upregulation of FcεRI on the abdominal vagus .…”

Advancing Lung Immunology Research: An Official American Thoracic Society Workshop Report

“…For instance, nociceptor neurons respond to inflammatory cytokines such as IL-4 as well as antibodies (58,59). Specifically, TRPV1 1 sensory neurons express the high-affinity IgE receptor FceR1 and respond to IgE-allergen immune complexes by releasing the neuropeptide SP (Substance P), which, in turn, amplifies Th2 cell production of IL-5 and IL-13 (58,(60)(61)(62). Albeit at lower surface amounts than in Th2 cells, B cell subtypes also express SP receptors.…”