Mast cell activation may explain many cases of chemical intolerance

Background This paper explores the relationship between chemical intolerance (CI) and mast cell activation syndrome (MCAS). Worldwide observations provide evidence for a two-stage disease process called toxicant-induced loss of tolerance (TILT) as a mechanism for CI. TILT is initiated by a major exposure event or a series of lower-level exposures. Subsequently, affected individuals report that common chemical inhalants, foods, and drugs (i.e., various xenobiotics) trigger multi-system symptoms. Purpose To determine whether MCAS provides a plausible biological mechanism for CI/TILT. Methods Using the validated Quick Environmental Exposure and Sensitivity Inventory (QEESI), we compared patients diagnosed with MCAS (n = 147) to individuals who reported chemical intolerances (CI/TILT) following various exposures (n = 345) and to healthy controls (n = 76). Using ANOVA, we compared QEESI scores across groups. Clinical scores for the MCAS patient group were used to predict CI status using logistic regression. Results More than half (59%) of the MCAS group met criteria for CI. A logistic regression model illustrates that as the likelihood of patients having MCAS increased, their likelihood of having CI/TILT similarly increased, to a near-perfect correspondence at the high ends of the QEESI and clinical MCAS scores. Symptom and intolerance patterns were nearly identical for the CI and MCAS groups. Discussion We present data suggesting that xenobiotic activation of mast cells may underlie CI/TILT. The strikingly similar symptom and intolerance patterns for MCAS and TILT suggest that xenobiotics disrupt mast cells, leading to either or both of these challenging conditions. Faced with patients suffering from complex illness affecting multiple organ systems and fluctuating inflammatory, allergic, and dystrophic symptoms, clinicians can now ask themselves two questions: (1) Could MCAS be at the root of these problems? (2) Could environmental exposures be driving MC activation and mediator release? Increasing our understanding of the connection between TILT and MCs has the potential to expose a new link between environmental exposures and illness, offering new opportunities for improving individual and public health. Conclusion The close correspondence between QEESI scores and symptom patterns for MCAS and TILT patients supports xenobiotic-driven mast cell activation and mediator release (i.e., MCAS) as a plausible unifying biological mechanism for CI/TILT, with profound implications for medicine, public health, and regulatory toxicology.

Mast Cell Sensitization as a Plausible and Researchable Mechanism for Chemical Intolerance

Background Worldwide observations provide evidence for a two-stage disease process called Toxicant-Induced Loss of Tolerance (TILT), described in this journal in the first of two related papers. The disease process is initiated by a major exposure event, or a series of lower level exposures (Stage I, Initiation). Subsequently, affected individuals report that common chemical inhalants, foods, and drugs trigger multisystem symptoms (Stage II, Triggering). Given that foods and drugs also are comprised of chemicals, we refer to these intolerances simply as “chemical intolerance” (CI). In this second, companion paper we propose mast cell sensitization and mediator release as a plausible and researchable biological explanation for TILT. Methods Using the Quick Environmental Exposure and Sensitivity Inventory (QEESI), we compared patients diagnosed with mast cell activation syndrome (MCAS) (n = 147) to individuals who reported chemical intolerances following various exposures (n = 345), and to controls (n = 76). We compared QEESI scores using ANOVA across groups. Clinical scores for the MCAS patient group were used to predict CI status using logistic regression. Results As the likelihood of patients’ having CI increased, their likelihood of having MCAS similarly increased, to a near-perfect correspondence at the high ends of the QEESI and clinical MCAS scores. Symptom patterns were near-identical for CI and MCAS groups. Conclusion The close correspondence between QEESI scores for MCAS and TILT patients supports mast cell sensitization and mediator release as a plausible biological mechanism underlying both conditions, with implications for medicine, environmental health, and regulatory toxicology.

Management of labor and delivery by spinal and epidural analgesia in a woman with systemic mastocytosis: a case report

Systemic mastocytosis is a life-threatening disease in which mast cell mediator release can lead to general symptoms. The most common triggers are stress and pain during labor and delivery. We report the management of labor and delivery in a case with severe systemic mastocytosis by epidural analgesia.

Purification and biochemical characterization of Hel a 6, a cross-reactive pectate lyase allergen from Sunflower (Helianthus annuus L.) pollen

Sunflower pollen was reported to contain respiratory allergens responsible for occupational allergy and pollinosis. The present study describes the comprehensive characterization of a major sunflower allergen Hel a 6. Natural Hel a 6 was purified from sunflower pollen by anion exchange and gel filtration chromatography. Hel a 6 reacted with IgE-antibodies from 57% of 39 sunflower-sensitized patient sera suggesting it to be a major allergen. The patients were of Indian origin and suffering from pollinosis and allergic rhinitis. Hel a 6 exhibited allergenic activity by stimulating mediator release from basophils. Monomeric Hel a 6 displayed pectate lyase activity. The effect of various physicochemical parameters such as temperature, pH, and calcium ion on the functional activity of Hel a 6 revealed a stable nature of the protein. Hel a 6 was folded, and its melting curve showed reversible denaturation in which it refolded back to its native conformation from a denatured state. Hel a 6 displayed a high degree of sequence conservation with the pectate lyase allergens from related taxonomic families such as Amb a 1 (67%) and Art v 6 (57%). The IgE-cross reactivity was observed between Hel a 6 and its ragweed and mugwort homologs. The cross-reactivity was further substantiated by the mediator release when Hel a 6-sensitized effector cells were cross-stimulated with Art v 6 and Amb a 1. Several putative B cell epitopes were predicted and mapped on these 3 allergens. Two antigenic regions were found to be commonly shared by these 3 allergens, which could be crucial for cross-reactivity. In conclusion, Hel a 6 serves as a candidate molecule for diagnosis and immunotherapy for weed allergy.