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Published ahead of print on November 17, 2005, doi:10.1164/rccm.200505-740OC
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American Journal of Respiratory and Critical Care Medicine Vol 173. pp. 370-378, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200505-740OC


Original Article

Complement C3a and C4a Increased in Plasma of Patients with Aspirin-induced Asthma

Seung-Ha Lee*, TaiYoun Rhim*, Yun-Sung Choi, Ji-Won Min, Sung-Ho Kim, Sun-Young Cho, Young-Ki Paik and Choon-Sik Park

Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Hospital, Bucheon; Department of Chemistry, Soonchunhyang University, Asan; and Yonsei Proteome Research Center, Seoul, Korea

Correspondence and requests for reprints should be addressed to Choon-Sik Park, M.D., Ph.D., Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Hospital, 1174, Jung-dong, Wonmi-gu, Bucheon-si, Gyeonggido 420-767, Republic of Korea. E-mail: mdcspark{at}unitel.co.kr

Rationale: Aspirin-induced asthma (AIA) is a distinct clinical syndrome that affects up to 10% of adults with asthma. Although eicosanoid metabolites appear to play an important role in AIA, the exact pathogenic mechanism for the syndrome remains obscure. In addition, the proposed mechanism fails to explain why aspirin does not cause bronchoconstriction in all individuals.

Objectives: We aimed to identify proteins that were differentially expressed in between AIA and aspirin-tolerant asthma (ATA) plasma.

Methods and Main Results: By using a proteomics approach, six proteins were found to be differentially expressed in plasma between patients with AIA and patients with ATA at baseline, and eight proteins were significantly up- or down-regulated after aspirin challenge in patients with AIA. These proteins, which were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, can be classified into four groups: complement components, apolipoproteins, modified albumin, and unknown proteins. Among them, the complement component levels in plasma were validated by using ELISA. Plasma concentrations of C3a and C4a were higher in patients with AIA (n = 30) than in patients with ATA (n = 24). After the aspirin challenge, C3 decreased in both patients with AIA and those with ATA, but the C3a concentration increased in the AIA patient group (p = 0.019). Moreover, C3a and C4a levels and the ratios of C3a/C3 and C4a/C4 were correlated with the changes of FEV1 values after aspirin challenge.

Conclusions: Aspirin intolerance may be related to alterations in the levels of complements, as well as those of lipoprotein and other proteins.

Key Words: aspirin-induced asthma • complement C3a and C4a • two-dimensional electrophoresis




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