ORIGINAL ARTICLE Serum total tryptase levels are increased in patients with active chronic urticaria M. Ferrer 1 , J. M. Nu ˜ nez-C´ ordoba 2 , E. Luquin 1 , C. E. Grattan 3 , J. M. De la Borbolla 1 , M. L. Sanz 1 , L. B. Schwartz 4 1 Department of Allergy and Clinical Immunology, Cl´ ınica Universidad de Navarra Medical School; 2 Department of Preventive Medicine and Public Health, Medical School, Universidad de Navarra, Pamplona, Spain; 3 Norfolk and Norwich University Hospital, Norwich, UK; and 4 Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA Clinical & Experimental Allergy Correspondence: M. Ferrer, Department of Allergy and Clinical Immunology, Cl´ ınica Universidad de Navarra, Pio XII, 36. 31008-Pamplona, Spain. E-mail: mferrerp@unav.es Cite this as: M. Ferrer, J. M. Nu˜ nez- C´ ordoba, E. Luquin, C. E. Grattan, J. M. De la Borbolla, M. L. Sanz, L. B. Schwartz, Clinical & Experimental Allergy , 2010 (40) 1760–1766. Summary Background We have demonstrated previously mast cell histamine release upon incubation with chronic urticaria (CU) sera, presumably by degranulation. Objective To explore total and mature tryptase in order to assess whether any increase in total tryptase levels is due in part to mast cell degranulation or to mast cell burden. We also wanted to explore differences between the autoimmune groups called idiopathic (serum unable to activate basophils), and to correlate total and mature tryptase levels with different urticaria features. Methods We measured total and mature tryptase serum levels in 81 CU patients, 16 atopic donors and 21 healthy control sera. We assessed autoimmunity by measuring the CD63 expression in normal basophil donors upon incubation with CU sera. Results We found significantly higher levels of total tryptase in the sera of CU patients (6.6 4.1 mg/L) than in sera from healthy non-atopic subjects (4.4 2.8 mg/L) and from atopic subjects (4.5 1.7 mg/L). Mature tryptase levels were undetectable (o1 ng/mL). Total tryptase levels in the autoimmune urticaria group were significantly higher (9.8 5.4 mg/L) than the idiopathic urticaria group (4.4 2.2 mg/L). A significant difference in total tryptase was found between symptomatic patients (7.3 4.1 mg/L) compared with asymptomatic ones (5.7 4.1 mg/L) at the time of venesection. No difference was found in mature tryptase levels either. Conclusion Total elevated tryptase levels are not accompanied by an elevated mature tryptase levels, as might be expected if the serum levels reflected mast cell degranulation. Keywords chronic urticaria, mast cells, tryptase Submitted 4 March 2010; revised 10 June 2010; accepted 18 June 2010 Introduction b-Tryptase is the major protein component of human mast cell secretory granules, accounting for as much as 20% of the total cell protein [1]. It is stored in secretory granules as a proteolytically active tetramer of 120 kDa that is bound to heparin or other proteoglycans through its cationic groove. a-Tryptase is the other form of soluble tryptase abundantly expressed by human mast cells. Both a- and b-protryptases are spontaneously released by resting cells, whereas primarily mature b-tryptase is stored in secretory granules and released by activated mast cells. Because a-protryptase does not undergo au- toprocessing, it may remain as a zymogen. Also, experi- mental preparations of mature recombinant a-tryptase are essentially inactive as a protease; and little if any mature or pro forms of a-tryptase have been detected in mast cell secretory granules. Two genes exist in the normal haploid genome for these tryptases: TPSB2, which is mono- morphic for b-tryptase, and TPSAB1, which is dimorphic, encoding an a-tryptase haplotype 50% of the time and a b-tryptase haplotype in the remaining subjects. Thus, about 25% of human subjects are completely deficient for the a-tryptase gene. Furthermore, portions of a- and b-protryptases are spontaneously released by resting mast cells. In contrast, mature b-tryptase is released when mast Clinical Mechanisms in Allergic Disease doi: 10.1111/j.1365-2222.2010.03582.x Clinical & Experimental Allergy, 40, 1760–1766  c 2010 Blackwell Publishing Ltd