immunology-congress-2018-posters-abstracts

Page 37

Notes:

allied

academies

Journal of Timely Topics in Clinical Immunology | Volume 2

July 26-28, 2018 | Moscow, Russia

Immunology

Annual Congress on

The monogenic disorder called alpha-tryptasemia fosters our understanding of the biologic and

pathobiologic roles of human α/β-tryptases

Lawrence B Schwartz

Virginia Common Wealth University, USA.

/β-Tryptases are preferentially expressed by mast cells

in humans, where they serve as biomarkers for systemic

anaphylaxis, systemic mastocytosis and mast cell cytoreductive

therapies. Their biologic or pathobiologic clinically-relevant

activities are less well understood. Recently, a monogenic

autosomal-dominant condition called alpha-tryptasemia has

been described due to a copy number variation in the gene

encodingalpha-tryptase,TPSAB1.Affectedpatientspresentwith

multi-organ system defects, including autonomic dysfunction,

joint hyper-extensibility, gastrointestinal symptoms and

vibratory urticaria along with elevated baseline tryptase levels,

but with a normal bone marrow biopsy and no c-kit mutation.

As α-tryptase tetramers are ineffective as proteases due to a

G245D change in which the aspartic acid side chain clogs the

substrate binding pocket, essentially all tryptase proteolytic

activity resides with β-tryptase, primarily via β-tryptase

tetramers, because monomers, when active, unlike tetramers,

are rapidly inactivated by biologic protease inhibitors. So how

might alpha-tryptasemia provide new insights in the function

of these tryptases? New research aiming to better understand

the relationship between tryptases and the clinical phenotype

of alpha-tryptasemia patients and how this might lead to

better therapeutic options for such patients will be discussed.