Evidence for Mast Cell Activation in Patients with Therapy-Resistant Irritable Bowel Syndrome

Frieling, Thomas; Meis, Kirsten; Kolck, Ulrich W.; Homann, Jürgen; Hülsdonk, A.; Haars, Ulrike; Hertfelder, Hans‐Jörg; Oldenburg, Johannes; Seidel, H.; Molderings, G. J.

doi:10.1055/s-0029-1245707

Cited by 34 publications

(21 citation statements)

References 18 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Evidence has been presented that MCAS may be an underlying cause of various frequent clinical presentations; for example, in subsets of patients with fibromyalgia [18], [19] and irritable bowel syndrome [20]. Accordingly, the prevalence of MCAS, and therewith that of MCAD, was expected to be at least within the single-figure percentage range [3].…”

Section: Discussionmentioning

confidence: 99%

Familial Occurrence of Systemic Mast Cell Activation Disease

et al. 2013

View full text Add to dashboard Cite

Systemic mast cell activation disease (MCAD) comprises disorders characterized by an enhanced release of mast cell mediators accompanied by accumulation of dysfunctional mast cells. Demonstration of familial clustering would be an important step towards defining the genetic contribution to the risk of systemic MCAD. The present study aimed to quantify familial aggregation for MCAD and to investigate the variability of clinical and molecular findings (e.g. somatic mutations in KIT) among affected family members in three selected pedigrees. Our data suggest that systemic MCAD pedigrees include more systemic MCAD cases than would be expected by chance, i.e., compared with the prevalence of MCAD in the general population. The prevalence of MCAD suspected by symptom self-report in first-degree relatives of patients with MCAD amounted to approximately 46%, compared to prevalence in the general German population of about 17% (p<0.0001). In three families with a high familial loading of MCAD, the subtype of MCAD and the severity of mediator-related symptoms varied between family members. In addition, genetic alterations detected in KIT were variable, and included mutations at position 816 of the amino acid sequence. In conclusion, our data provide evidence for common familial occurrence of MCAD. Our findings observed in the three pedigrees together with recent reports in the literature suggest that, in familial cases (i.e., in the majority of MCAD), mutated disease-related operator and/or regulator genes could be responsible for the development of somatic mutations in KIT and other proteins important for the regulation of mast cell activity. Accordingly, the immunohistochemically different subtypes of MCAD (i.e. mast cell activation syndrome and systemic mastocytosis) should be more accurately regarded as varying presentations of a common generic root process of mast cell dysfunction, than as distinct diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Familial Occurrence of Systemic Mast Cell Activation Disease

et al. 2013

View full text Add to dashboard Cite

show abstract

“…17) as in irritable bowel syndrome (IBS, increasingly linked to MCA (e.g. 18,19))), and in different sites (e.g. co-existing (heparin-induced) osteoporosis and (histamine-induced) osteosclerosis (e.g.…”

Section: Presentationmentioning

confidence: 99%

Often seen, rarely recognized: mast cell activation disease – a guide to diagnosis and therapeutic options

et al. 2016

View full text Add to dashboard Cite

Mast cell (MC) disease has long been thought to be just the rare disease of mastocytosis (in various forms, principally cutaneous and systemic), with aberrant MC mediator release at symptomatic levels due to neoplastic MC proliferation. Recent discoveries now show a new view is in order, with mastocytosis capping a metaphorical iceberg now called "MC activation disease" (MCAD, i.e. disease principally manifesting inappropriate MC activation), with the bulk of the iceberg being the recently recognized "MC activation syndrome" (MCAS), featuring inappropriate MC activation to symptomatic levels with little to no inappropriate MC proliferation. Given increasing appreciation of a great menagerie of mutations in MC regulatory elements in mastocytosis and MCAS, the great heterogeneity of MCAD's clinical presentation is unsurprising. Most MCAD patients present with decades of chronic multisystem polymorbidity generally of an inflammatory ± allergic theme. Preliminary epidemiologic investigation suggests MCAD, while often misrecognized, may be substantially prevalent, making it increasingly important that practitioners of all stripes learn how to recognize its more common forms such as MCAS. We review the diagnostically challenging presentation of MCAD (with an emphasis on MCAS) and current thoughts regarding its biology, epidemiology, natural history, diagnostic evaluation, and treatment.

show abstract

“…There are three forms of MCAD, the most prevalent is mast cell activation syndrome (MCAS), followed by systemic mastocytosis, then mast cell leukemia (Haenisch et al, 2012). Additionally, MCAS has been implicated as an underlying cause of fibromyalgia (Lucas et al, 2006) and irritable bowel syndrome (Frieling et al, 2011). There are however, no reports of humans with mast cells deficiencies to aid in the deciphering of their physiological roles in human physiology.…”

Section: Mast Cell Biologymentioning

confidence: 99%

Are mast cells instrumental for fibrotic diseases?

et al. 2014

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disorder of unknown etiology characterized by accumulation of lung fibroblasts and extracellular matrix deposition, ultimately leading to compromised tissue architecture and lung function capacity. IPF has a heterogeneous clinical course; however the median survival after diagnosis is only 3–5 years. The pharmaceutical and biotechnology industry has made many attempts to find effective treatments for IPF, but the disease has so far defied all attempts at therapeutic intervention. Clinical trial failures may arise for many reasons, including disease heterogeneity, lack of readily measurable clinical end points other than overall survival, and, perhaps most of all, a lack of understanding of the underlying molecular mechanisms of the progression of IPF. The precise link between inflammation and fibrosis remains unclear, but it appears that immune cells can promote fibrosis by releasing fibrogenic factors. So far, however, therapeutic approaches targeting macrophages, neutrophils, or lymphocytes have failed to alter disease pathogenesis. A new cell to garner research interest in fibrosis is the mast cell. Increased numbers of mast cells have long been known to be present in pulmonary fibrosis and clinically correlations between mast cells and fibrosis have been reported. More recent data suggests that mast cells may contribute to the fibrotic process by stimulating fibroblasts resident in the lung, thus driving the pathogenesis of the disease. In this review, we will discuss the mast cell and its physiological role in tissue repair and remodeling, as well as its pathological role in fibrotic diseases such as IPF, where the process of tissue repair and remodeling is thought to be dysregulated.

show abstract

Evidence for Mast Cell Activation in Patients with Therapy-Resistant Irritable Bowel Syndrome

Cited by 34 publications

References 18 publications

Familial Occurrence of Systemic Mast Cell Activation Disease

Familial Occurrence of Systemic Mast Cell Activation Disease

Often seen, rarely recognized: mast cell activation disease – a guide to diagnosis and therapeutic options

Are mast cells instrumental for fibrotic diseases?

Contact Info

Product

Resources

About