Mast Cell Activation in Ehlers-Danlos Syndrome

This post describes a review article (Mast cell disorders in Ehlers-Danlos syndrome) about the role of mast cells in Ehlers Danlos syndrome (EDS), which was published in 2017 in the American Journal of Medical Genetics: Seminars in Medical Genetics. Mast cells are immune cells that are primarily located in tissues throughout the body including connective tissue which are key sites affected during EDS. Mast cells play an important role in initiating and promoting immune responses to pathogens (i.e., viruses, bacteria) and toxins (i.e., bee stings, mold) by releasing different kinds of chemical mediators such as histamine, tryptase and chymase within minutes of their activation. Mast cells (MC) have a role in both allergic and non-allergic diseases by responding with IgE-mediated (allergy) and IgG-mediated (non-allergy) responses. One disease that mast cells are involved in are connective tissue disorders (CTD) such as EDS and its subtypes including hypermobile EDS (hEDS) and Hypermobility Spectrum Disorder (HSD). This review article describes several studies that have found links between EDS, especially the hypermobile type, and mast cell activation disorder (MCAD). Immunohistochemistry analysis identified an increased chymase (mast cell product) content in undamaged skin of patients with signs of connective tissue disorders. Several reports describing comorbid clinical manifestations in patients with CTDs and MCAD including functional gastrointestinal disorders, eosinophilic gastrointestinal disorders, increased prevalence of asthma, neuropsychiatric conditions, osteoporosis, and orthostatic intolerance.

A past article (Cosegregation of postural orthostatic tachycardia syndrome, hypermobile Ehlers-Danlos syndrome, and mast cell activation syndrome) in Annals of Allergy, Asthma & Immunology describes symptoms compatible with a non-IgE-mediated mast cell disorder in patients with joint hypermobility syndrome with a positive response to classical MC/MC mediator antagonists but normal levels of plasma histamine and serum tryptase. Immunologist Dr. Peter Vadas and his colleagues have suggested (A New Disease Cluster: Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome, and Ehlers-Danlos Syndrome) a possible new disease cluster with patients having mast cell activation syndrome (MCAS), postural orthostatic tachycardia syndrome (POTS) and EDS, but the causes between them is not yet clear. 66% of patients with POTS and EDS also had MCAS symptoms. Authors in Nature Genetics identified (Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number) families with an elevated baseline serum tryptase, which was associated with the triad of dysautonomia, MCAD and joint hypermobility. The observations from these papers show increasing evidence that mast cell activation can be associated with connective tissue diseases like hEDS/HSD. More research to come! Stay connected here as we explore these topics in future posts.

 Authors: Archana Kotha, MD, Katelyn Bruno, PhD, and DeLisa Fairweather, PhD