Mast cell disorders in Ehlers–Danlos syndrome

Abstract

Well known for their role in allergic disorders, mast cells (MCs) play a key role in homeostatic mechanisms and surveillance, recognizing and responding to different pathogens, and tissue injury, with an array of chemical mediators. After being recruited to connective tissues, resident MCs progenitors undergo further differentiation, under the influence of signals from surrounding microenvironment. It is the differential tissue homing and local maturation factors which result in a diverse population of resident MC phenotypes. An abundance of MC reside in connective tissue that borders with the external world (the skin as well as gastrointestinal, respiratory, and urogenital tracts). Situated near nerve fibers, lymphatics, and blood vessels, as well as coupled with their ability to secrete potent mediators, MCs can modulate the function of local and distant structures (e.g., other immune cell populations, fibroblasts, angiogenesis), and MC dysregulation has been implicated in immediate and delayed hypersensitivity syndromes, neuropathies, and connective tissue disorders (CTDs). This report reviews basic biology of mast cells and mast cell activation as well as recent research efforts, which implicate a role of MC dysregulation beyond atopic disorders and in a cluster of Ehlers-Danlos Syndromes, non-IGE mediated hypersensitivity disorders, and dysautonomia.

Utilization of the 2017 diagnostic criteria for hEDS by the Toronto GoodHope Ehlers–Danlos syndrome clinic: A retrospective review

“…Patients with hEDS may present with a number of comorbid features including widespread pain, orthostatic intolerance (OI) and/or postural orthostatic tachycardia syndrome (POTS) (Hakim et al, ), chronic headaches (Henderson et al, ), gastrointestinal (GI) dysfunction and functional disorders (Fikree, Chelimsky, Collins, Kovacic, & Aziz, ), mast cell activation syndrome (MCAS) (Seneviratne, Maitland, & Afrin, ), and psychological comorbidities such as depression and anxiety (Bulbena et al, ).…”

Mast cells—Good guys with a bad image?

“…34 Arrived at their destination, MCs mature from their precursors under the influence of the stem cell factor (SCF) in humans or combined action of SCF and interleukin (IL)-3 in rodents. 34 Arrived at their destination, MCs mature from their precursors under the influence of the stem cell factor (SCF) in humans or combined action of SCF and interleukin (IL)-3 in rodents.…”

“…border to the environment, for example the skin, the gastrointestinal tract, the respiratory tract, and also the reproductive tract. 34 Arrived at their destination, MCs mature from their precursors under the influence of the stem cell factor (SCF) in humans or combined action of SCF and interleukin (IL)-3 in rodents. 35 Also other growth factors and cytokines of the local microenvironment like IL-4, IL-6, IL-9, IL-10, interferonγ, and the nerve growth factor can influence maturation, differentiation, proliferation, and apoptosis of MCs.…”

Rheumatological presentation of Bartonella koehlerae and Bartonella henselae bacteremias

“…Recent research supports a potential role for mast cell activation and dysregulation in a subset of nongenetically mediated EDS patients with joint hypermobility syndrome. [6] In addition to the lung and gastrointestinal tract, mast cells are prevalent in cutaneous tissues throughout the body. [6] In the context of a plausible pathogenesis, a long-standing Bartonella spp.…”

“…[6] In addition to the lung and gastrointestinal tract, mast cells are prevalent in cutaneous tissues throughout the body. [6] In the context of a plausible pathogenesis, a long-standing Bartonella spp. infection, accompanied by chronic mast cell activation could potentially contribute to ongoing damage to connective tissues; thereby resulting in clinical findings indicative of EDS.…”