臺灣博碩士論文加值系統

氣喘是一種常見的慢性呼吸道疾病，導致喘鳴音、呼吸困難、胸悶和咳嗽。據估計，目前全世界約有3億人口罹患氣喘，且盛行率逐年上升。氣喘是一種終身性疾病，數目日益增加的氣喘患者除了造成個人與家庭的困擾外，更增加了治療氣喘的醫療資源及其他相關社會成本沈重的負擔。蛋白質醣基化是目前已知的轉譯後修飾作用之一，參與大量的生命活動，在生物標記研究中具重要意義。本研究即利用醣蛋白質體學方法，嘗試蒐尋和氣喘疾病相關的血漿生物標記。藉由凝集素–刀豆素A (Concanavalin A, Con A) 對醣基之高度親和性純化出血漿中的醣蛋白質，同時去除血漿中其他未醣基化之大量高豐度蛋白質。經二維電泳及影像分析比對顯示：氣喘患者和非氣喘患者血漿中的五個醣蛋白質色點區域具有顯著差異，進一步以質譜儀鑑定這些醣蛋白質之身份，分別是Ig gamma-1 chain、β-2-glycoprotein 1、Haptoglobin、Dermcidin、Complement C3、α-2-macroglobulin、Hemoglobin subunit β 與 δ。採用西方轉印法加以驗證，標記優先進行驗證根據三個標準，首先，在膠片上有一致性的趨勢，再根據該蛋白質與氣喘關連性的相關文獻多寡，最後針對疾病的專一性作篩選，選擇α-2-macroglobulin 作為驗證，從實驗得知α-2-macroglobulin為具有潛力之血漿生物標記，可以提供臨床診斷，以早期偵測或是發展新穎藥物提供治療。

Asthma is a common chronic respiratory disease that leads to wheezing, breathlessness, chest tightness and coughing. Asthma is a problem worldwide, with estimated about 300 million affected individuals, and the prevalence is increasing year by year. Asthma is a lifelong disease, an increasing number of patients with asthma caused personal and family distress, and more medical resources on the treatment of asthma and other social costs associated with a heavy burden. Protein glycosylation is currently known as one of the post-translational modifications, involved in a large number of biological functions, and played an important role in biomarker studies. In the current study, we used glycoproteomic approaches for the identification of potential disease biomarkers from plasma of patients with asthma. We purified glycoproteins in plasma obtained from asthma and non-asthma patients based on concanavalin A (Con A) -affinity method. With this treatment, a large number of high-abundance non-glycosylated proteins could be removed. Two-dimensional electrophoresis and image analysis revealed five protein spots with significantly different expression levels between asthma and non-asthma patients. These protein spots have been in-gel digested and subject to LC-ESI-Q-TOF MS/MS and Mascot program analysis. Protein identified are Ig gamma-1 chain, β-2-glycoprotein1, haptoglobin, dermcidin, complement C3, α-2-macroglobulin, hemoglobin subunit β and δ. Western blot analysis were performed to validate the proteomic results, the marking based on the three criteria, The first, the film has a consistent trend;second, the related protein associated with asthma amount of literature. Finally, the specificity of the disease for screening, Alpha-2-macroglobulin are asthma-associated plasma protein. These potential biomarkers may be developed as promising diagnostic indicators for the early detection of the disease or development of novel drugs or providing treatment.

中文摘要 I
Abstract II
壹、前言 1
一、過敏性氣喘 1
(一)流行病學 2
(二) 過敏機制 3
(三) 引起氣喘因素 4
(四) 特徵及臨床症狀 5
(五) 診斷 6
(六) 預防與治療 7
二、蛋白質體學 8
三、生物標記 10
四、醣蛋白質 11
五、凝集素 14
貳、研究目的 17
參、實驗材料及儀器 18
一、檢體樣品 19
二、材料 19
(一)蛋白質純化及定量 19
(二) SDS-PAGE和二維凝膠電泳 19
(三)西方轉印法 20
三、實驗器材 21
肆、實驗方法 23
一、實驗流程 23
二、Concanavalin A純化 23
三、蛋白質定量 24
四、十二烷基硫酸鈉聚丙烯醯胺凝膠電泳(Sodium Dodecyl Sulfate Polyacrylamide gel
electrophoresis, SDS-PAGE ) 25
(一)醣染色 26
(二) Brilliant Blue G染色 27
五、二維電泳分析(Two-dimensional gel electrophoresis, 2-DE) 27
(一)第一維：等電點聚焦電泳 27
(二)第二維：十二烷基硫酸鈉聚丙烯醯胺凝膠電泳 29
六、影像比對 29
七、膠體裁切 30
八、膠體內水解與液相層析串聯質譜儀 (LC-ESI-Q-TOF MS /MS) 分析 30
九、西方轉印法 (Western blot) 31
伍、結果 33
一、分析對照組及實驗組檢體樣品個體差異 34
二、確認純化過程與Con A純化前後的差異 34
三、以二維電泳搜尋具有潛力的醣蛋白質 35
四、經液相層析串聯質譜儀 (LC-ESI-Q-TOF MS /MS) 鑑定結果 35
五、西方轉印法結果 35
六、IPA資料庫分析結果 36
陸、討論 38
一、有效搜尋氣喘疾病之生物標記方法 38
二、蛋白質身分之探討 38
三、經蛋白質體學分析結果與氣喘疾病相關探討 38
(一) Ig gamma-1 chain 38
(二) β-2-glycoprotein 1 39
(三) Haptoglobin 40
(四) Dermcidin 41
(五) Complement C3 42
(六) α-2-macroglobulin 43
(七) Hemoglobin 44
四、驗證 45
柒、結論 46
捌、圖表附件 47
玖、參考文獻 83

王自豪, 林誠謙, & 李弘謙. (2002). 談蛋白質折疊與氨基酸序列. 物理雙月刊, 24(2), 320-327.
吳家興, 林瑞雄, 謝貴雄, 邱文達, 陳麗美, 邱淑媞, 黃國晉, 劉文良, 邱宏毅, 蕭慧娟, 方淑慧, 陳雄文, 林嘉明&宋鴻樟. (1998). 台灣北部國中學生氣喘盛行率調查. 中華公共衛生雜誌, 17(3), 214-215.
江伯倫. (2002). 過敏性疾病的致病機轉. 科學發展, 353, 14-19.
洪仁宇, & 黃吉志. (2007). 氣喘的定義及診斷. 高醫醫訊月刊, 19(10).
胡笳, 郭燕婷, & 李艷梅. (2005). 蛋白質翻譯後修飾研究進展. 科學通報, 50(11), 1061-1072.
陳頌方, 黎培鈺, & 沈蕙如. (2007). 找尋生物指標的利器：差異蛋白質體學分析平台之簡介. 中國化學, 65(2), 211-224.
馮翠霞. (1996). 氣喘照護之最新趨勢. 長庚護理, 7(1), 66-74.
黃群峰. (2006). 台灣東部地區學童過敏疾病盛行率調查及過敏原研究-以花蓮縣玉里鎮全鎮國小學童為研究對象. 國立中山大學生物醫學研究所碩士論文, 1-48.
楊小玉. (2001). 氣喘病患之日常生活保健. 臺大醫網, 11, 18-20.
楊雪慧. (2007). 蛋白體學的應用─生物標記的發現. 中國化學, 65( 3), 281-285.
邓宇斌. (1997). 抗磷脂抗体的共辅因子β2GPI的研究进展. 上海免疫学杂志, 17(1), 61-62.
Ağar, , Groot, P. G. D., & Meijers, J. C. M. (2012). Structural Changes in β2-Glycoprotein I and the Antiphospholipid Syndrome. Antiphospholipid Syndrome, 23-34.
Agostinis, C., Biffi, S., Garrovo, C., Durigutto, P., Lorenzon, A., Bek, A., Bulla, R., Grossi, C., Borghi, M. O., Meroni, P., & Tedesco, F. (2011). In vivo distribution of beta2 glycoprotein I under various pathophysiologic conditions. Blood, 118(15), 4231-4238.
Ahmed, N., Barker, G., Oliva, K., Garfin, D., Talmadge, K., Georgiou, H., Quinn, M., & Rice, G. (2003). An approach to remove albumin for the proteomic analysis of low abundance biomarkers in human serum. Proteomics, 3(10), 1980-1987.
Ali, H., & Panettieri, R. A. (2005). Anaphylatoxin C3a receptors in asthma. Respir Res, 6, 1-6.
Alvarez-Manilla, G., Warren, N. L., Atwood, J., Orlando, R., Dalton, S., & Pierce, M. (2010). Glycoproteomic Analysis of Embryonic Stem Cells: Identification of Potential Glycobiomarkers Using Lectin Affinity Chromatography of Glycopeptides. Received September, 9, 2062–2075.
Ammitzboll, C. G., Thiel, S., Ellingsen, T., Deleuran, B., Jorgensen, A., Jensenius, J. C., & Stengaard-Pedersen, K. (2012). Levels of lectin pathway proteins in plasma and synovial fluid of rheumatoid arthritis and osteoarthritis. Rheumatol Int, 32(5), 1457-1463.
Bahadori, K., Doyle-Waters, M. M., Marra, C., Lynd, L., Alasaly, K., Swiston, J., & Fitzgerald, J. M. (2009). Economic burden of asthma: a systematic review. BMC Pulm Med, 9, 24.
Baker, M. (2005). In biomarkers we trust? Nature biotechnology, 23(3), 297-304.
Bao, Z., Lim, S., Liao, W., Lin, Y., Thiemermann, C., Leung, B. P., & Wong, W. S. (2007). Glycogen synthase kinase-3beta inhibition attenuates asthma in mice. Am J Respir Crit Care Med, 176(5), 431-438.
Bartels, A. L., Kortekaas, R., Bart, J., Willemsen, A., De Klerk, O. L., De Vries, J. J., Van Oostrom, J. C., & Leenders, K. L. (2009). Blood–brain barrier P-glycoprotein function decreases in specific brain regions with aging: a possible role in progressive neurodegeneration. Neurobiology of aging, 30(11), 1818-1824.
Bellei, E., Bergamini, S., Monari, E., Fantoni, L. I., Cuoghi, A., Ozben, T., & Tomasi, A. (2011). High-abundance proteins depletion for serum proteomic analysis: concomitant removal of non-targeted proteins. Amino Acids, 40(1), 145-156.
Bloemen, K., Heuvel, R. V. D., Govarts, E., Hooyberghs, J., Nelen, V., Witters, E., Desager, K., & Schoeters, G. (2010). A new approach to study exhaled proteins as potential biomarkers for asthma. Clinical & Experimental Allergy, 41, 346-356.
Bosnjak, B., Stelzmueller, B., Erb, K. J., & Epstein, M. M. (2011). Treatment of allergic asthma: modulation of Th2 cells and their responses. Respir Res, 12, 114.
Bousquet, J., Clark, T. J. H., Skhaltaev, H., N. , Lenfant, C., O'byrne, P., & Sheffer, A. (2007). GINA guidelines on asthma and beyond. Allergy, 62, 102-112.
Center for Environmental Health (2008). Asthma and the school environment in new york state. 1-74.
Chang, W., Huang, M., Yang, C., Wang, W., Lai, T., Hsiao, M., & Chen, C. (2010). Dermcidin identification from exhaled air for lung cancer diagnosis. European Respiratory Journal, 35(5), 1182-1185.
Chen, J., Xi, J., Yuan, T., Bova, G. S., & Zhang, H. (2013). Identification, prioritization and evaluation of glycoproteins for aggressive prostate cancer using quantitative glycoproteomics and antibody-based assays on tissue specimens. Proteomics, 1-24.
Chen, R., Tan, Y., Wang, M., Wang, F., Yao, Z., Dong, L., Ye, M., Wang, H., & Zou, H. (2011). Development of Glycoprotein Capture-Based Label-Free Method for the High-throughput Screening of Differential Glycoproteins in Hepatocellular Carcinoma. Molecular & Cellular Proteomics, 10, 1–13.
Chen, Z., & Gu, J. (2007). Immunoglobulin G expression in carcinomas and cancer cell lines. FASEB J, 21(11), 2931-2938.
Cho, S. Y., Lee, E. Y., Lee, J. S., Kim, H. Y., Park, J. M., Kwon, M. S., Park, Y. K., Lee, H. J., Kang, M. J., Kim, J. Y., Yoo, J. S., Park, S. J., Cho, J. W., Kim, H. S., & Paik, Y. K. (2005). Efficient prefractionation of low-abundance proteins in human plasma and construction of a two-dimensional map. Proteomics, 5(13), 3386-3396.
Choe, J., Zhang, F., Wolff, M. W., Murhammer, D. W., Linhardt, R. J., & Dordick, J. S. (2000). Separation of alpha-Acid Glycoprotein Glycoforms Using Affinity-Based Reversed Micellar Extraction and Separation. Biotechnol Bioeng, 70, 484-490.
Choi, E., Loo, D., Dennis, J. W., O'leary, C. A., & Hill, M. M. (2011). High‐throughput lectin magnetic bead array‐coupled tandem mass spectrometry for glycoprotein biomarker discovery. Electrophoresis, 32(24), 3564-3575.
Ci, X., Chu, X., Wei, M., Yang, X., Cai, Q., & Deng, X. (2012). Different effects of farrerol on an OVA-induced allergic asthma and LPS-induced acute lung injury. PloS one, 7(4), e34634.
Collins, F., Lander, E., Rogers, J., Waterston, R., & Conso, I. (2004). Finishing the euchromatic sequence of the human genome. Nature, 431(7011), 931-945.
Cui, K.-H. (1995). Genome project and human reproduction. Molecular Human Reproduction, 1(111-115).
Dai, Z., Zhou, J., Qiu, S.-J., Liu, Y.-K., & Fan, J. (2009). Lectin-based glycoproteomics to explore and analyze hepatocellular carcinoma-related glycoprotein markers. 30, 2957–2966.
Dasgupta, S., Samtani, R., & Saraswathy, K. (2008). Haptoglobin Polymorphism among Warli Tribe of Dadra Nagar Haveli, India. Anthropologist, 10(4), 315-316.
Drake, P. M., Schilling, B., Niles, R. K., Braten, M., Johansen, E., Liu, H., Lerch, M., Sorensen, D. J., Li, B., Allen, S., Hall, S. C., Witkowska, H. E., Regnier, F. E., Gibson, B. W., & Fisher, S. J. (2010). A lectin affinity workflow targeting glycosite-specific, cancer-related carbohydrate structures in trypsin-digested human plasma. Anal Biochem, 408(1), 71-85.
Fattah, M. A., Baz, M. E., Sherif, A., & Adel, A. (2010). Complement components (C3, C4) as inflammatory markers in asthma. Indian J Pediatr, 77(7), 771-773.
Feng, J.-T., Wu, X.-M., Li, X.-Z., Zou, Y.-Q., Qin, L., & Hu, C.-P. (2012). Transformation of adrenal medullary chromaffin cells increases asthmatic susceptibility in pups from allergen-sensitized rats. Respir Res, 13(1), 99.
Ferreira, J. A., Daniel-Da-Silva, A. L., Alves, R. M. P., Duarte, D., Vieira, I., Santos, L. L., Vitorino, R., & Amado, F. (2011). Synthesis and optimization of lectin functionalized nanoprobes for the selective recovery of glycoproteins from human body fluids. Anal Chem, 83(18), 7035-7043.
Fischetti, F., Durigutto, P., Pellis, V., Debeus, A., Macor, P., Bulla, R., Bossi, F., Ziller, F., Sblattero, D., Meroni, P., & Tedesco, F. (2005). Thrombus formation induced by antibodies to beta2-glycoprotein I is complement dependent and requires a priming factor. Blood, 106(7), 2340-2346.
Fu, Y. (2002). Detection of Differentially Expressed Genes in Cancer Using Differential Display. Methods in Molecular Medicine, 68, 179-193.
Gagliardo, R., Chanez, P., Profita, M., Bonanno, A., Albano, G. D., Montalbano, A. M., Pompeo, F., Gagliardo, C., Merendino, A. M., & Gjomarkaj, M. (2011). IkappaB kinase-driven nuclear factor-kappaB activation in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol, 128(3), 635-645 e631-632.
Glovsky, M. M., Ward, P. A., & Johnson, K. J. (2004). Complement determinations in human disease. Ann Allergy Asthma Immunol, 93, 513-523.
Gropp, K., Weber, N., Reuter, M., Micklisch, S., Kopka, I., Hallström, T., & Skerka, C. (2011). beta(2)-glycoprotein I, the major target in antiphospholipid syndrome, is a special human complement regulator. Blood, 118(10), 2774-2783.
Guo, Y. L., Lin, Y.-C., Sung, F.-C., Huang, S.-L., Ko, Y.-C., Lai, J.-S., Su, H.-J., Shaw, C.-K., Lin, R.-S., & Dockery, D. W. (1999). Climate, Traffic-Related Air Pollutants, and Asthma Prevalence in Middle-School Children in Taiwan. Environmental Health Perspectives, 107(12), 1001-1006.
Hart, C., & Schulenberg, B. S., Thomas H. Leung, Wai-Yee Patton, Wayne F. . (2003). Detection of glycoproteins in polyacrylamide gels and on electroblots using Pro-Q Emerald 488 dye, a fluorescent periodate Schiff-base stain. Electrophoresis, 24, 588–598.
Health, N. C. F. E., & Effects, D. O. E. H. a. H. (2001). Asthma in the US. CDC Vital signs.
Huang, Z. Y., Kim, M. K., Kim-Han, T. H., Indik, Z. K., & Schreiber, A. D. (2013). Effect of locally administered Syk siRNA on allergen-induced arthritis and asthma. Mol Immunol, 53(1-2), 52-59.
Ioannou, Y., Zhang, J.-Y., Passam, F. H., Rahgozar, S., Qi, J. C., Giannakopoulos, B., Qi, M., Yu, P., Yu, D. M., Hogg, P. J., & Krilis, S. A. (2010). Naturally occurring free thiols within beta 2-glycoprotein I in vivo: nitrosylation, redox modification by endothelial cells, and regulation of oxidative stress-induced cell injury. Blood, 116(11), 1961-1970.
Jia, G., Erickson, R. W., Choy, D. F., Mosesova, S., Wu, L. C., Solberg, O. D., Shikotra, A., Carter, R., Audusseau, S., Hamid, Q., Bradding, P., Fahy, J. V., Woodruff, P. G., Harris, J. M., & Arron, J. R. (2012). Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol, 130(3), 647-654.
Jiménez, S., Tàssies, D., Espinosa, G., García-Criado, A., Plaza, J., Monteagudo, J., Cervera, R., & Reverter, J. C. (2008). Double heterozygosity polymorphisms for platelet glycoproteins Ia/IIa and IIb/IIIa increases arterial thrombosis and arteriosclerosis in patients with the antiphospholipid syndrome or with systemic lupus erythematosus. Annals of the rheumatic diseases, 67(6), 835-840.
Jonge, H. J., Fehrmann, R. S., De Bont, E. S., Hofstra, R. M., Gerbens, F., Kamps, W. A., Vries, E. G., Van Der Zee, A. G., Te Meerman, G. J., & Ter Elst, A. (2007). Evidence based selection of housekeeping genes. PloS one, 2(9), e898.
Kang, S., Sung, H., Ahn, J., Park, J., Lee, S., Park, C., & Cho, J. (2011). The Haptoglobin β chain as a supportive biomarker for human lung cancers. Mol Biosyst, 7(4), 1167-1175.
Kimata, H. (2007). Increase in dermcidin-derived peptides in sweat of patients with atopic eczema caused by a humorous video. J Psychosom Res, 62(1), 57-59.
Kuno, A., Kato, Y., Matsuda, A., Kaneko, M. K., Ito, H., Amano, K., Chiba, Y., Narimatsu, H., & Hirabayashi, J. (2008). Focused Differential Glycan Analysis with the Platform Antibody-assisted Lectin Profiling for Glycan-related Biomarker Verification. Molecular & Cellular Proteomics, 8(1), 99-108.
Lai, C. K. W., Guia, T. S. D., Kim, Y.-Y., Kuo, S.-H., Mukhopadhyay, A., Soriano, J. B., Trung, P. L., Zhong, N. S., Zainudin, N., & Zainudin, B. M. Z. (2003). Asthma control in the Asia-Pacific region: the Asthma Insights and Reality in Asia-Pacific Study. J Allergy Clin Immunol, 111(2), 263-268.
Lai, C. K. W., Kim, Y.-Y., Kuo, S.-H., Spencer, M., & Williams, A. E. (2006). Cost of asthma in the Asia-Pacific region. European Respiratory Review, 15(98), 10-16.
Larsen, K., Macleod, D., Nihlberg, K., Marko-Varga, E. G., & Westergren-Thorsson, G. (2006). Specific Haptoglobin Expression in Bronchoalveolar Lavage during Differentiation of Circulating Fibroblast Progenitor Cells in Mild Asthma. J Proteome Res., 5(6), 1479-1483.
Lee, S.-H., Kim, K.-H., Kim, J.-M., Yoon, S.-H., Kim, T. H., Park, S.-W., Park, J.-S., Uh, S.-T., Lee, H. S., Kim, Y. H., Kang, J. H., Chung, I. Y., Paik, Y. K., Rhim, T., & Park, C.-S. (2011). Relationship between group-specific component protein and the development of asthma. Am J Respir Crit Care Med, 184(5), 528-536.
Legrain, P., Aebersold, R., Archakov, A., Bairoch, A., Bala, K., Beretta, L., Bergeron, J., Borchers, C. H., Corthals, G. L., & Costello, C. E. (2011). The human proteome project: current state and future direction. Molecular & Cellular Proteomics, 10(7).
Lin, R., Caveliere, L., Lorenzana, F., Go, E., & Altman, K. (2004). Pattern of C3, iC3b, and C3d in patients hospitalized for acute asthma. Ann Allergy, 68(4), 324-330.
Liu, F., Zaidi, T., Iqbal, K., Grundke-Iqbal, I., Merkle, R. K., & Gong, C.-X. (2002). Role of glycosylation in hyperphosphorylation of tau in Alzheimer’s disease. FEBS letters, 512(1), 101-106.
Lopez, L. R., Kobayashi, K., Matsunami, Y., & Matsuura, E. (2009). Immunogenic oxidized low-density lipoprotein/beta2-glycoprotein I complexes in the diagnostic management of atherosclerosis. Clin Rev Allergy Immunol, 37(1), 12-19.
Maddux, B. A., Sbraccia, P., Kumakura, S., Sasson, S., Youngren, J., Fisher, A., Spencer, S., Grupe, A., Henzel, W., & Stewart, T. A. (1995). Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus.
Magnani, J. L., Steplewski, Z., & Koprowski, H. (1983). Identification of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 19-9 in the sera of patients as a mucin. Cancer Research, 43, 5489-5492.
Masoli, M., Fabian, D., Holt, S., & Beasley, R. (2004). The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy, 59, 469-478.
Mcdonald, C. A., Yang, J. Y., Marathe, V., Yen, T.-Y., & Macher, B. A. (2009). Combining Results from Lectin Affinity. Molecular & Cellular Proteomics, 8, 287–301.
Mirarabshahi, P., Abdelatti, M., & Krilis, S. (2012). Post-translational oxidative modification of beta2-glycoprotein I and its role in the pathophysiology of the antiphospholipid syndrome. Autoimmun Rev, 11(11), 779-780.
Moriya, S., Morimoto, M., Numata, K., Nozaki, A., Shimoyama, Y., Kondo, M., Nakano, M., Maeda, S., & Tanaka, K. (2013). Fucosylated Fraction of Alpha-fetoprotein as a Serological. ANTICANCER RESEARCH, 33, 997-1002.
Mosca, T., Menezes, M. C. S. D., Dionigi, P. C. L., Stirbulov, R., & Forte, W. C. N. (2011). C3 and C4 complement system components as biomarkers in the intermittent atopic asthma diagnosis. J Pediatr, 87(6), 512-516.
Najam, F. I. E., Giasuddin, A. S. M., & Shembesh, A. H. (2005). Complement Components (C3, C4) in Childhood Asthma. Indian J Pediatr, 72(9), 745-749.
Nakano, Y., Morita, S., Kawamoto, A., Suda, T., Chida, K., & Nakamura, H. (2003). Elevated complement C3a in plasma from patients with severe acute asthma. J Allergy Clin Immunol., 112(3), 525-530.
Nicolaides, N. C., Holroyd, K. J., Ewart, S. L., Eleff, S. M., Kiser, M. B., Dragwa, C. R., Sullivan, C. D., Grasso, L., Zhang, L.-Y., & Messler, C. J. (1997). Interleukin 9: a candidate gene for asthma. Proceedings of the National Academy of Sciences, 94(24), 13175-13180.
Omenn, G. S. (2004). The Human Proteome Organization Plasma Proteome Project pilot phase: reference specimens, technology platform comparisons, and standardized data submissions and analyses. Proteomics, 4(5), 1235-1240.
Oxelius, V. (2012). From genotypes of immunoglobulin constant heavy G chains (Fcγ) (GM) genes (IGHG) to phenotypes in childhood asthma. Int Arch Allergy Immunol. , 159(1), 94-102.
Passam, F. H., Giannakopoulos, B., Mirarabshahi, P., & Krilis, S. A. (2011). Molecular pathophysiology of the antiphospholipid syndrome: the role of oxidative post-translational modification of beta 2 glycoprotein I. J Thromb Haemost, 9 Suppl 1, 275-282.
Passam, F. H., Tanaka, J. C. Q., K. , Matthaei, K. I., & Krilis, S. A. (2010). In vivo modulation of angiogenesis by beta 2 glycoprotein I. J Autoimmun, 35(3), 232-240.
Patchell, B. J., & Dorscheid, D. R. (2006). Repair of the injury to respiratory epithelial cells characteristic of asthma is stimulated by Allomyrina dichotoma agglutinin specific serum glycoproteins. Clin Exp Allergy, 36(5), 585-593.
Paulmann, M., Arnold, T., Linke, D., Ozdirekcan, S., Kopp, A., Gutsmann, T., Kalbacher, H., Wanke, I., Schuenemann, V. J., Habeck, M., Bürck, J., Ulrich, A. S., & Schittek, B. (2012). Structure-activity analysis of the dermcidin-derived peptide DCD-1L, an anionic antimicrobial peptide present in human sweat. J Biol Chem, 287(11), 8434-8443.
Perisic, T., Sreckovic, M., & Matic, G. (2007). An imbalance in antioxidant enzymes and stress proteins in childhood asthma. Clin Biochem, 40(15), 1168-1171.
Petric, T. C., Brne, P., Gabor, B., Govednik, L., Barut, M., Strancar, A., & Kralj, L. Z. (2007). Anion-exchange chromatography using short monolithic columns as a complementary technique for human serum albumin depletion prior to human plasma proteome analysis. J Pharm Biomed Anal, 43(1), 243-249.
Poulter, E. Y., Truszkowski, P., Thompson, A. A., & Liem, R. I. (2011). Acute chest syndrome is associated with history of asthma in hemoglobin SC disease. Pediatr Blood Cancer, 57(2), 289-293.
Rahgozar, S. (2012). Revisiting Beta 2 Glycoprotein I, the Major Autoantigen in the Antiphospholipid Syndrome. Iran J Immunol, 9(2), 73-85.
Rava, M., Ahmed, I., Demenais, F., Sanchez, M., Tubert-Bitter, P., & Nadif, R. (2013). Selection of genes for gene-environment interaction studies: a candidate pathway-based strategy using asthma as an example. Environmental Health, 12(1), 56.
Rhim, T., Choi, Y.-S., Nam, B.-Y., Uh, S. T., Park, J. S., Kim, Y.-H., Paik, Y.-K., & Park, C.-S. (2009). Plasma protein profiles in early asthmatic responses to inhalation allergen challenge. Allergy, 64(1), 47-54.
Rieg, S., Garbe, C., Sauer, B., Kalbacher, H., & Schittek, B. (2004). Dermcidin is constitutively produced by eccrine sweat glands and is not induced in epidermal cells under inflammatory skin conditions. British Journal of Dermatology, 151, 524-539.
Rieg, S., Steffen, H., Seeber, S., Humeny, A., Kalbacher , H., Dietz, K., Garbe, C., & Schittek, B. (2005). Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. J Immunol, 174(12), 8003-8010.
Ring, J., Krämer, U., Schäfer, T., & Behrendt, H. (2001). Why are allergies increasing? Allergy and hypersensitivity, 13, 701-708.
Roche, N., Stirling, R. G., Lim, S., Oliver, B. G., Oates, T., Jazrawi, E., Caramori, G., & Chung, K. F. (2003). Effect of acute and chronic inflammatory stimuli on expression of protease-activated receptors 1 and 2 in alveolar macrophages. Journal of Allergy and Clinical Immunology, 111(2), 367-373.
Rui Chen, Y. T., Min Wang, Fangjun Wang, Zhenzhen Yao,Liwei Dong, Mingliang Ye, Hongyang Wang, and Hanfa Zou. (2011). Development of Glycoprotein Capture-Based.
Sadrzadeh, S. M. H., & Bozorgmehr, J. (2004). Haptoglobin Phenotypes in Health and Disorders. Pathology Patterns Reviews, 121(1), 97-104.
Sahu, A., & Lambris, J. D. (2001). Structure and biology of complement protein C3, a connecting link between innate and acquired immunity. Immunological Reviews, 180, 35-48.
Saroha, A., Biswas, S., Chatterjee, B. P., & Das, H. R. (2011). Altered glycosylation and expression of plasma alpha-1-acid glycoprotein and haptoglobin in rheumatoid arthritis. J Chromatogr B Analyt Technol Biomed Life Sci, 879(20), 1839-1843.
Schittek, B. (2012). The multiple facets of dermcidin in cell survival and host defense. J Innate Immun, 4(4), 349-360.
Schoonbrood, D. F., Lutter, R., Habets, F. J., Roos, C. M., Jansen, H. M., & Out, T. A. (1994). Analysis of plasma-protein leakage and local secretion in sputum from patients with asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 150, 1519-1527.
Seny, D. D., Fillet, M., Meuwis, M. A., Geurts, P., Lutteri, L., Ribbens, C., Bours, V., Wehenkel, L., Piette, J., Malaise, M., & Merville, M. P. (2005). Discovery of new rheumatoid arthritis biomarkers using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry ProteinChip approach. Arthritis Rheum, 52(12), 3801-3812.
Shakib, F., & Smith, S. J. (1994). In vitro basophil histamine-releasing activity of circulating IgG1 and IgG4 autoanti-IgE antibodies from asthma patients and the demonstration that anti-IgE modulates allergen-induced basophil activation. Clinical & Experimental Allergy, 24(3), 270-275.
Sin, D. D., & Sutherland, E. R. (2008). Obesity and the lung: 4. Obesity and asthma. Thorax, 63(11), 1018-1023.
Sinz, A., Bantscheff, M., Mikkat, S., Ringel, B., Drynda, S., Kekow, J., Thiesen, H.-J., & Glocker, M. O. (2002). Mass spectrometric proteome analyses of synovial fluids and plasmas from patients suffering from rheumatoid arthritis and comparison to reactive arthritis or osteoarthritis. Electrophoresis, 23, 3445-3456.
Skoner, D. P. (2001). Allergic rhinitis: Definition, epidemiology, pathophysiology, detection, and diagnosis. Journal of Allergy and Clinical Immunology, 108(1), S2-S8.
Sok, D., Clarizia, L.-J. A., Farris, L. R., & Mcdonald, M. J. (2009). Novel fluoroimmunoassay for ovarian cancer biomarker CA-125. Analytical and bioanalytical chemistry, 393(5), 1521-1523.
Stenman, U.-H., Leinonen, J., & Alfthan, H. (1991). A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer assay of the complex improves clinical sensitivity. Cancer Research, 52, 222-226.
Subbarao, P., Mandhane, P. J., & Sears, M. R. (2009). Asthma: epidemiology, etiology and risk factors. CMAJ, 181(9), E181-190.
Sun, Y., Yu, W., Huang, L., Hou, J., Gong, P., Zheng, Y., Zhao, M., Zhou, P., & Li, X. (2012). Is Asthma Related to Choroidal Neovascularization? PLoS One., 7(5), 1-9.
Tirumalai, R. S. C., King C. , Prieto, D. A., Issaq, H. J., Conrads, T. P., & Veenstra, T. D. (2003). Characterization of the Low Molecular Weight Human Serum Proteome. Molecular & Cellular Proteomics, 2, 1096–1103.
Tomita, K., Caramori, G., Ito, K., Sano, H., Lim, S., Oates, T., Cosio, B., Chung, K. F., Tohda, Y., Barnes, P. J., & Adcock, I. M. (2012). STAT6 expression in T cells, alveolar macrophages and bronchial biopsies of normal and asthmatic subjects. J Inflamm (Lond), 9, 5.
Triche, E. W., Lundsberg, L. S., Wickner, P. G., Belanger, K., Leaderer, B. P., & Bracken, M. B. (2011). Association of maternal anemia with increased wheeze and asthma in children. Ann Allergy Asthma Immunol, 106(2), 131-139 e131.
Urbas, L., Brne, P., Gabor, B., Barut, M., Strlic, M., Petric, T. C., & Strancar, A. (2009). Depletion of high-abundance proteins from human plasma using a combination of an affinity and pseudo-affinity column. J Chromatogr A, 1216(13), 2689-2694.
Verrills, N. M., Irwin, J. A., He, X. Y., Wood, L. G., Powell, H., Simpson, J. L., Mcdonald, V. M., Sim, A., & Gibson, P. G. (2011). Identification of novel diagnostic biomarkers for asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 183(12), 1633-1643.
Wagner, B., Greiser-Wilke, I., Wege, A. K., Radbruch, A., & Leibold, W. (2002). Evolution of the six horse IGHG genes and corresponding immunoglobulin gamma heavy chains. Immunogenetics, 54(5), 353-364.
Wain, H. M., Lush, M. J., Ducluzeau, F., Khodiyar, V. K., & Povey, S. (2004). Genew: the human gene nomenclature database, 2004 updates. Nucleic Acids Res, 32(suppl 1), D255-D257.
Wang, S., & Li, Y. (2006). Progress in Glycomics. Chinese Journal of Cell Biology, 28, 127-131.
Wang, Y., Chen, Y., Zhang, Y., Wu, S., Ma, S., Hu, S., Zhang, L., Shao, C., Li, M., & Gao, Y. (2008). Differential ConA-enriched urinary proteome in rat experimental glomerular diseases. Biochem Biophys Res Commun, 371(3), 385-390.
Watson, J. D., & Crick, F. H. C. (1953). A structure for deoxyribose nucleic acid. Nature, 3, 171, 737-738.
Wu, C. H., Apweiler, R., Bairoch, A., Natale, D. A., Barker, W. C., Boeckmann, B., Ferro, S., Gasteiger, E., Huang, H., Lopez, R., Magrane, M., Martin, M. J., Mazumder, R., O'donovan, C., Redaschi, N., & Suzek, B. (2006). The Universal Protein Resource (UniProt): an expanding universe of protein information. Nucleic Acids Res, 34(Database issue), D187-191.
Xu, G., Cheng, L., Lu, L., Zhu, Y., Xu, R., Yao, X., & Li, H. (2008). Expression of T-cell immunoglobulin- and mucin-domain-containing molecule-1 (TIM-1) is increased in a mouse model of asthma and relationship to GATA-3. Life Sci, 82(11-12), 663-669.
Yang, F., Ghio, A. J., Herbert, D. C., Weaker, F. J., Walter, C. A., & Coalson, J. J. (2000). Pulmonary Expression of the Human Haptoglobin Gene. American Journal of Respiratory Cell and Molecular Biology, 23, 277-282.
Zivanovic, S., Rackov, L. P., Vojvodic, D., & Vucetic, D. (2009). Human cartilage glycoprotein 39--biomarker of joint damage in knee osteoarthritis. Int Orthop, 33(4), 1165-1170.