FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 337:1720-1725 December 11, 1997 Number 24 Next

The Association of Atopy with a Gain-of-Function Mutation in the Subunit of the Interleukin-4 Receptor

	Full Text PDF Letters Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Atopic diseases are very common, and atopy has a strong genetic predisposition.

Methods Using single-strand conformation polymorphism analysis and DNA sequencing, we searched for mutations in the subunit of the interleukin-4 receptor that would predispose persons to atopy. We examined the prevalence of the alleles among patients with allergic inflammatory disorders and among 50 prospectively recruited adults. Subjects with atopy were identified on the basis of an elevated serum lgE level (>95 IU per milliliter) or a positive radioimmunosorbent test in response to standard inhalant allergens. The signaling function of mutant interleukin-4 receptor was examined by flow cytometry, binding assays, and immunoblotting.

Results A novel interleukin-4 receptor allele was identified in which guanine was substituted for adenine at nucleotide 1902, causing a change from glutamine to arginine at position 576 (R576) in the cytoplasmic domain of the interleukin-4 receptor protein. The R576 allele was common among patients with allergic inflammatory disorders (found in 3 of 3 patients with the hyper-IgE syndrome and 4 of 7 patients with severe atopic dermatitis) and among the 50 prospectively recruited adults (found in 13 of 20 subjects with atopy and 5 of 30 without atopy; P = 0.001; relative risk of atopy among those with a mutant allele, 9.3). The R576 allele was associated with higher levels of expression of CD23 by interleukin-4 than the wild-type allele. This enhanced signaling was associated with a change in the binding specificity of the adjacent tyrosine residue at position 575 to signal-transducing molecules.

Conclusions The R576 allele of interleukin-4 receptor is strongly associated with atopy. This mutation may predispose persons to allergic diseases by altering the signaling function of the receptor.

Source Information

From the Departments of Pediatrics (G.K.K.H., M.F.F., L.A.E., T.A.C.) and Pathology (M.L.T., T.A.C.), Howard Hughes Medical Institute (M.L.T.), and the Center for Immunology (M.L.T., T.A.C.), Washington University School of Medicine, St. Louis.

Address reprint requests to Dr. Chatila at the Division of Immunology–Rheumatology, Department of Pediatrics, Washington University School of Medicine, 1 Children's Pl., St. Louis, MO 63110.

Full Text of this Article

Related Letters:

Acid–Base Disorders
Marik P., Varon J., Rao R. B., Hoffman R. S., Skorecki K., Bistrian B. R., McCowen K. C., Driscoll D., Adrogué H. J., Madias N. E.
Extract | Full Text  
N Engl J Med 1998; 338:1626-1629, May 28, 1998. Correspondence

Atopy and a Mutation in the Interleukin-4 Receptor Gene
Dupre D., Audrezet M.-P., Ferec C., Chatila T.
Extract | Full Text  
N Engl J Med 2000; 343:69-70, Jul 6, 2000. Correspondence

This article has been cited by other articles:

• Tachdjian, R., Mathias, C., Al Khatib, S., Bryce, P. J., Kim, H. S., Blaeser, F., O'Connor, B. D., Rzymkiewicz, D., Chen, A., Holtzman, M. J., Hershey, G. K., Garn, H., Harb, H., Renz, H., Oettgen, H. C., Chatila, T. A. (2009). Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma. JEM 206: 2191-2204 [Abstract] [Full Text]  
• Ford, A. Q., Heller, N. M., Stephenson, L., Boothby, M. R., Keegan, A. D. (2009). An Atopy-Associated Polymorphism in the Ectodomain of the IL-4R{alpha} Chain (V50) Regulates the Persistence of STAT6 Phosphorylation. J. Immunol. 183: 1607-1616 [Abstract] [Full Text]  
• Pillemer, B. B. L., Qi, Z., Melgert, B., Oriss, T. B., Ray, P., Ray, A. (2009). STAT6 Activation Confers upon T Helper Cells Resistance to Suppression by Regulatory T Cells. J. Immunol. 183: 155-163 [Abstract] [Full Text]  
• Speiran, K., Bailey, D. P., Fernando, J., Macey, M., Barnstein, B., Kolawole, M., Curley, D., Watowich, S. S., Murray, P. J., Oskeritzian, C., Ryan, J. J. (2009). Endogenous suppression of mast cell development and survival by IL-4 and IL-10. J. Leukoc. Biol. 85: 826-836 [Abstract] [Full Text]  
• Oh, S. Y., Zheng, T., Kim, Y.-K., Cohn, L., Homer, R. J., McKenzie, A. N. J., Zhu, Z. (2009). A Critical Role of SHP-1 in Regulation of Type 2 Inflammation in the Lung. Am. J. Respir. Cell Mol. Bio. 40: 568-574 [Abstract] [Full Text]  
• Wills-Karp, M., Finkelman, F. D. (2008). Untangling the Complex Web of IL-4- and IL-13-Mediated Signaling Pathways. Sci Signal 1: pe55-pe55 [Abstract] [Full Text]  
• Zhu, J., Paul, W. E. (2008). CD4 T cells: fates, functions, and faults. Blood 112: 1557-1569 [Abstract] [Full Text]  
• Ueta, M., Sotozono, C., Inatomi, T., Kojima, K., Hamuro, J., Kinoshita, S. (2008). Association of Combined IL-13/IL-4R Signaling Pathway Gene Polymorphism with Stevens-Johnson Syndrome Accompanied by Ocular Surface Complications. IOVS 49: 1809-1813 [Abstract] [Full Text]  
• Yang, H., Gu, J., Lin, X., Grossman, H. B., Ye, Y., Dinney, C. P., Wu, X. (2008). Profiling of Genetic Variations in Inflammation Pathway Genes in Relation to Bladder Cancer Predisposition. Clin. Cancer Res. 14: 2236-2244 [Abstract] [Full Text]  
• Scirica, C. V., Celedon, J. C. (2007). Genetics of Asthma: Potential Implications for Reducing Asthma Disparities. Chest 132: 770S-781S [Abstract] [Full Text]  
• Wenzel, S. E., Balzar, S., Ampleford, E., Hawkins, G. A., Busse, W. W., Calhoun, W. J., Castro, M., Chung, K. F., Erzurum, S., Gaston, B., Israel, E., Teague, W. G., Curran-Everett, D., Meyers, D. A., Bleecker, E. R. (2007). IL4R{alpha} Mutations Are Associated with Asthma Exacerbations and Mast Cell/IgE Expression. Am. J. Respir. Crit. Care Med. 175: 570-576 [Abstract] [Full Text]  
• Park, H.-W., Shin, E.-S., Lee, J.-E., Kwon, H.-S., Chun, E., Kim, S.-S., Chang, Y.-S., Kim, Y.-K., Min, K.-U., Kim, Y.-Y., Cho, S.-H. (2007). Multilocus analysis of atopy in Korean children using multifactor-dimensionality reduction. Thorax 62: 265-269 [Abstract] [Full Text]  
• Shiroiwa, W., Tsukamoto, K., Ohtsuji, M., Lin, Q., Ida, A., Kodera, S., Ohtsuji, N., Nakamura, K., Tsurui, H., Kinoshita, K., Nishimura, H., Shirai, T., Hirose, S. (2007). IL-4R{alpha} polymorphism in regulation of IL-4 synthesis by T cells: implication in susceptibility to a subset of murine lupus. Int Immunol 19: 175-183 [Abstract] [Full Text]  
• Webb, D. C., Cai, Y., Matthaei, K. I., Foster, P. S. (2007). Comparative Roles of IL-4, IL-13, and IL-4R{alpha} in Dendritic Cell Maturation and CD4+ Th2 Cell Function. J. Immunol. 178: 219-227 [Abstract] [Full Text]  
• Bailey, D. P., Kashyap, M., Bouton, L. A., Murray, P. J., Ryan, J. J. (2006). Interleukin-10 induces apoptosis in developing mast cells and macrophages. J. Leukoc. Biol. 80: 581-589 [Abstract] [Full Text]  
• Truyen, E, Coteur, L, Dilissen, E, Overbergh, L, Dupont, L J, Ceuppens, J L, Bullens, D M A (2006). Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement in sputum of asthma patients. Thorax 61: 202-208 [Abstract] [Full Text]  
• Georas, S. N., Guo, J., De Fanis, U., Casolaro, V. (2005). T-helper cell type-2 regulation in allergic disease. Eur Respir J 26: 1119-1137 [Abstract] [Full Text]  
• Stephenson, L. M., Park, D.-S., Mora, A. L., Goenka, S., Boothby, M. (2005). Sequence Motifs in IL-4R{alpha} Mediating Cell-Cycle Progression of Primary Lymphocytes. J. Immunol. 175: 5178-5185 [Abstract] [Full Text]  
• Steck, A. K., Bugawan, T. L., Valdes, A. M., Emery, L. M., Blair, A., Norris, J. M., Redondo, M. J., Babu, S. R., Erlich, H. A., Eisenbarth, G. S., Rewers, M. J. (2005). Association of Non-HLA Genes With Type 1 Diabetes Autoimmunity. Diabetes 54: 2482-2486 [Abstract] [Full Text]  
• Stephenson, L., Johns, M. H., Woodward, E., Mora, A. L., Boothby, M. (2004). An IL-4R{alpha} Allelic Variant, I50, Acts as a Gain-of-Function Variant Relative to V50 for Stat6, But Not Th2 Differentiation. J. Immunol. 173: 4523-4528 [Abstract] [Full Text]  
• Lim, M. S., Elenitoba-Johnson, K. S.J. (2004). The Molecular Pathology of Primary Immunodeficiencies. J. Mol. Diagn. 6: 59-83 [Full Text]  
• Gillespie, S. R., DeMartino, R. R., Zhu, J., Chong, H. J., Ramirez, C., Shelburne, C. P., Bouton, L. A., Bailey, D. P., Gharse, A., Mirmonsef, P., Odom, S., Gomez, G., Rivera, J., Fischer-Stenger, K., Ryan, J. J. (2004). IL-10 Inhibits Fc{epsilon}RI Expression in Mouse Mast Cells. J. Immunol. 172: 3181-3188 [Abstract] [Full Text]  
• Webb, D. C., Matthaei, K. I., Cai, Y., McKenzie, A. N. J., Foster, P. S. (2004). Polymorphisms in IL-4R{alpha} Correlate with Airways Hyperreactivity, Eosinophilia, and Ym Protein Expression in Allergic IL-13-/- Mice. J. Immunol. 172: 1092-1098 [Abstract] [Full Text]  
• Faffe, D. S., Whitehead, T., Moore, P. E., Baraldo, S., Flynt, L., Bourgeois, K., Panettieri, R. A., Shore, S. A. (2003). IL-13 and IL-4 promote TARC release in human airway smooth muscle cells: role of IL-4 receptor genotype. Am. J. Physiol. Lung Cell. Mol. Physiol. 285: L907-L914 [Abstract] [Full Text]  
• Bruns, H. A., Schindler, U., Kaplan, M. H. (2003). Expression of a Constitutively Active Stat6 In Vivo Alters Lymphocyte Homeostasis with Distinct Effects in T and B Cells. J. Immunol. 170: 3478-3487 [Abstract] [Full Text]  
• He, J.-Q., Connett, J. E., Anthonisen, N. R., Sandford, A. J. (2003). Polymorphisms in the IL13, IL13RA1, and IL4RA Genes and Rate of Decline in Lung Function in Smokers. Am. J. Respir. Cell Mol. Bio. 28: 379-385 [Abstract] [Full Text]  
• Szefler, S. J. (2003). Pediatric Asthma: An Approach to Pharmacogenetics Analysis. Chest 123 : 434S-438S [Full Text]  
• Hanson, E. M., Dickensheets, H., Qu, C.-K., Donnelly, R. P., Keegan, A. D. (2003). Regulation of the Dephosphorylation of Stat6. PARTICIPATION OF TYR-713 IN THE INTERLEUKIN-4 RECEPTOR alpha , THE TYROSINE PHOSPHATASE SHP-1, AND THE PROTEASOME. J. Biol. Chem. 278: 3903-3911 [Abstract] [Full Text]  
• Wong, G. W., Foster, P. S., Yasuda, S., Qi, J. C., Mahalingam, S., Mellor, E. A., Katsoulotos, G., Li, L., Boyce, J. A., Krilis, S. A., Stevens, R. L. (2002). Biochemical and Functional Characterization of Human Transmembrane Tryptase (TMT)/Tryptase gamma . TMT IS AN EXOCYTOSED MAST CELL PROTEASE THAT INDUCES AIRWAY HYPERRESPONSIVENESS IN VIVO VIA AN INTERLEUKIN-13/INTERLEUKIN-4 RECEPTOR alpha /SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION (STAT) 6-DEPENDENT PATHWAY. J. Biol. Chem. 277: 41906-41915 [Abstract] [Full Text]  
• Calhoun, E. S., McGovern, R. M., Janney, C. A., Cerhan, J. R., Iturria, S. J., Smith, D. I., Gostout, B. S., Persing, D. H. (2002). Host Genetic Polymorphism Analysis in Cervical Cancer. Clin. Chem. 48: 1218-1224 [Abstract] [Full Text]  
• Nakamura, E., Megumi, Y., Kobayashi, T., Kamoto, T., Ishitoya, S., Terachi, T., Tachibana, M., Matsushiro, H., Habuchi, T., Kakehi, Y., Ogawa, O. (2002). Genetic Polymorphisms of the Interleukin-4 Receptor{alpha} Gene Are Associated with an Increasing Risk and a Poor Prognosis of Sporadic Renal Cell Carcinoma in a Japanese Population. Clin. Cancer Res. 8: 2620-2625 [Abstract] [Full Text]  
• Risma, K. A., Wang, N., Andrews, R. P., Cunningham, C. M., Ericksen, M. B., Bernstein, J. A., Chakraborty, R., Hershey, G. K. K. (2002). V75R576 IL-4 Receptor {alpha} Is Associated with Allergic Asthma and Enhanced IL-4 Receptor Function. J. Immunol. 169: 1604-1610 [Abstract] [Full Text]  
• Lordan, J. L., Bucchieri, F., Richter, A., Konstantinidis, A., Holloway, J. W., Thornber, M., Puddicombe, S. M., Buchanan, D., Wilson, S. J., Djukanovic, R., Holgate, S. T., Davies, D. E. (2002). Cooperative Effects of Th2 Cytokines and Allergen on Normal and Asthmatic Bronchial Epithelial Cells. J. Immunol. 169: 407-414 [Abstract] [Full Text]  
• Perez-G., M., Melo, M., Keegan, A. D., Zamorano, J. (2002). Aspirin and Salicylates Inhibit the IL-4- and IL-13-Induced Activation of STAT6. J. Immunol. 168: 1428-1434 [Abstract] [Full Text]  
• Reich, K., Heine, A., Hugo, S., Blaschke, V., Middel, P., Kaser, A., Tilg, H., Blaschke, S., Gutgesell, C., Neumann, C. (2001). Engagement of the Fc{epsilon}RI Stimulates the Production of IL-16 in Langerhans Cell-Like Dendritic Cells. J. Immunol. 167: 6321-6329 [Abstract] [Full Text]  
• Howard, T. D., Whittaker, P. A., Zaiman, A. L., Koppelman, G. H., Xu, J., Hanley, M. T., Meyers, D. A., Postma, D. S., Bleecker, E. R. (2001). Identification and Association of Polymorphisms in the Interleukin-13 Gene with Asthma and Atopy in a Dutch Population. Am. J. Respir. Cell Mol. Bio. 25: 377-384 [Abstract] [Full Text]  
• Komiya, I., Yamada, T., Sato, A., Kouki, T., Nishimori, T., Takasu, N. (2001). Remission and Recurrence of Hyperthyroid Graves' Disease during and after Methimazole Treatment When Assessed by IgE and Interleukin 13. J. Clin. Endocrinol. Metab. 86: 3540-3544 [Abstract] [Full Text]  
• Daley, T., Metcalfe, D. D., Akin, C. (2001). Association of the Q576R polymorphism in the interleukin-4 receptor {alpha} chain with indolent mastocytosis limited to the skin. Blood 98: 880-882 [Abstract] [Full Text]  
• White, E. D., Andrews, R. P., Hershey, G. K. K. (2001). Sulfhydryl-2 domain-containing protein tyrosine phosphatase-1 is not a negative regulator of interleukin-4 signaling in murine mast cells. J. Leukoc. Biol. 69: 825-830 [Abstract] [Full Text]  
• Sakai, T., Matsuoka, M., Aoki, M., Nosaka, K., Mitsuya, H. (2001). Missense mutation of the interleukin-12 receptor {beta}1 chain-encoding gene is associated with impaired immunity against Mycobacterium avium complex infection. Blood 97: 2688-2694 [Abstract] [Full Text]  
• Donnadieu, E., Cookson, W. O., Jouvin, M.-H., Kinet, J.-P. (2000). Allergy-Associated Polymorphisms of the Fc{epsilon}RI{beta} Subunit Do Not Impact Its Two Amplification Functions. J. Immunol. 165: 3917-3922 [Abstract] [Full Text]  
• Buchs, N., Silvestri, T., di Giovine, F. S., Chabaud, M., Vannier, E., Duff, G. W., Miossec, P. (2000). IL-4 VNTR gene polymorphism in chronic polyarthritis. The rare allele is associated with protection against destruction. Rheumatology (Oxford) 39: 1126-1131 [Abstract] [Full Text]  
• Palmer, L. J., Cookson, W. O.C.M. (2000). Genomic Approaches to Understanding Asthma. Genome Res 10: 1280-1287 [Abstract] [Full Text]  
• SAVELKOUL, H. F. J. (2000). Immune Parameters in High-risk Atopic Individuals during Early Childhood. Am. J. Respir. Crit. Care Med. 162: S100-104 [Full Text]  
• POSTMA, D. S., KOPPELMAN, G. H., MEYERS, D. A. (2000). The Genetics of Atopy and Airway Hyperresponsiveness. Am. J. Respir. Crit. Care Med. 162: S118-123 [Full Text]  
• Hilliquin, P., Allanore, Y., Coste, J., Renoux, M., Kahan, A., Menkes, C. J. (2000). Reduced incidence and prevalence of atopy in rheumatoid arthritis. Results of a case-control study. Rheumatology (Oxford) 39: 1020-1026 [Abstract] [Full Text]  
• Dupre, D., Audrezet, M.-P., Ferec, C., Chatila, T. (2000). Atopy and a Mutation in the Interleukin-4 Receptor Gene. NEJM 343: 69-70 [Full Text]  
• Nakayama, E. E., Hoshino, Y., Xin, X., Liu, H., Goto, M., Watanabe, N., Taguchi, H., Hitani, A., Kawana-Tachikawa, A., Fukushima, M., Yamada, K., Sugiura, W., Oka, S.-I., Ajisawa, A., Sato, H., Takebe, Y., Nakamura, T., Nagai, Y., Iwamoto, A., Shioda, T. (2000). Polymorphism in the Interleukin-4 Promoter Affects Acquisition of Human Immunodeficiency Virus Type 1 Syncytium-Inducing Phenotype. J. Virol. 74: 5452-5459 [Abstract] [Full Text]  
• Hunt, P. J., Marshall, S. E., Weetman, A. P., Bell, J. I., Wass, J. A. H., Welsh, K. I. (2000). Cytokine Gene Polymorphisms in Autoimmune Thyroid Disease. J. Clin. Endocrinol. Metab. 85: 1984-1988 [Abstract] [Full Text]  
• PATUZZO, C., TRABETTI, E., MALERBA, G., MARTINATI, L. C., BONER, A. L, PESCOLLDERUNGG, L., ZANONI, G., PIGNATTI, P. F. (2000). No linkage or association of the IL-4Ralpha gene Q576R mutation with atopic asthma in Italian families. J. Med. Genet. 37: 382-384 [Full Text]  
• Hadeiba, H., Corry, D. B., Locksley, R. M. (2000). Baseline Airway Hyperreactivity in A/J Mice Is not Mediated by Cells of the Adaptive Immune System. J. Immunol. 164: 4933-4940 [Abstract] [Full Text]  
• GAO, P-S, MAO, X-Q, ROBERTS, M H, ARINOBU, Y, AKAIWA, M, ENOMOTO, T, DAKE, Y, KAWAI, M, SASAKI, S, HAMASAKI, N, IZUHARA, K, SHIRAKAWA, T, HOPKIN, J M (2000). Variants of STAT6 (signal transducer and activator of transcription 6) in atopic asthma. J. Med. Genet. 37: 380a-382 [Full Text]  
• Fujio, K., Nosaka, T., Kojima, T., Kawashima, T., Yahata, T., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Yamamoto, K., Nishimura, T., Kitamura, T. (2000). Molecular cloning of a novel type 1 cytokine receptor similar to the common gamma chain. Blood 95: 2204-2210 [Abstract] [Full Text]  
• Mein, C. A., Barratt, B. J., Dunn, M. G., Siegmund, T., Smith, A. N., Esposito, L., Nutland, S., Stevens, H. E., Wilson, A. J., Phillips, M. S., Jarvis, N., Law, S., de Arruda, M., Todd, J. A. (2000). Evaluation of Single Nucleotide Polymorphism Typing with Invader on PCR Amplicons and Its Automation. Genome Res 10: 330-343 [Abstract] [Full Text]  
• SANDFORD, A. J., PARE, P. D. (2000). The Genetics of Asthma . The Important Questions. Am. J. Respir. Crit. Care Med. 161: S202-206 [Full Text]  
• Huang, H., Paul, W. E. (2000). Protein Tyrosine Phosphatase Activity Is Required for IL-4 Induction of IL-4 Receptor {alpha}-Chain. J. Immunol. 164: 1211-1215 [Abstract] [Full Text]  
• Kruse, S., Forster, J., Kuehr, J., Deichmann, K. A. (1999). Characterization of the membrane-bound and a soluble form of human IL-4 receptor {alpha} produced by alternative splicing. Int Immunol 11: 1965-1970 [Abstract] [Full Text]  
• Janas, M. L., Hodgkin, P., Hibbs, M., Tarlinton, D. (1999). Genetic Evidence for Lyn as a Negative Regulator of IL-4 Signaling. J. Immunol. 163: 4192-4198 [Abstract] [Full Text]  
• Chung, K F, Barnes, P J (1999). Cytokines in asthma. Thorax 54: 825-857 [Full Text]  
• Srikiatkhachorn, A., Chang, W., Braciale, T. J. (1999). Induction of Th-1 and Th-2 Responses by Respiratory Syncytial Virus Attachment Glycoprotein Is Epitope and Major Histocompatibility Complex Independent. J. Virol. 73: 6590-6597 [Abstract] [Full Text]  
• NOGUCHI, E., SHIBASAKI, M., ARINAMI, T., TAKEDA, K., YOKOUCHI, Y., KOBAYASHI, K., IMOTO, N., NAKAHARA, S., MATSUI, A., HAMAGUCHI, H. (1999). No Association between Atopy/Asthma and the Ile50val Polymorphism of IL-4 Receptor. Am. J. Respir. Crit. Care Med. 160: 342-345 [Abstract] [Full Text]  
• Wang, H. Y., Shelburne, C. P., Zamorano, J., Kelly, A. E., Ryan, J. J., Keegan, A. D. (1999). Cutting Edge: Effects of an Allergy-Associated Mutation in the Human IL-4R{alpha} (Q576R) on Human IL-4-Induced Signal Transduction. J. Immunol. 162: 4385-4389 [Abstract] [Full Text]  
• Grimbacher, B., Holland, S. M., Gallin, J. I., Greenberg, F., Hill, S. C., Malech, H. L., Miller, J. A., O'Connell, A. C., Puck, J. M. (1999). Hyper-IgE Syndrome with Recurrent Infections -- An Autosomal Dominant Multisystem Disorder. NEJM 340: 692-702 [Abstract] [Full Text]  
• Wierenga, E. A., Walchner, M., Kick, G., Kapsenberg, M. L., Weiss, E. H., Messer, G. (1999). Evidence for suppressed activity of the transcription factor NFAT1 at its proximal binding element P0 in the IL-4 promoter associated with enhanced IL-4 gene transcription in T cells of atopic patients. Int Immunol 11: 297-306 [Abstract] [Full Text]  
• Mitsuyasu, H., Yanagihara, Y., Mao, X.-Q., Gao, P.-S., Arinobu, Y., Ihara, K., Takabayashi, A., Hara, T., Enomoto, T., Sasaki, S., Kawai, M., Hamasaki, N., Shirakawa, T., Hopkin, J. M., Izuhara, K. (1999). Cutting Edge: Dominant Effect of Ile50Val Variant of the Human IL-4 Receptor {alpha}-Chain in IgE Synthesis. J. Immunol. 162: 1227-1231 [Abstract] [Full Text]  
• Matsumoto, M., Ra, C., Kawamoto, K., Sato, H., Itakura, A., Sawada, J., Ushio, H., Suto, H., Mitsuishi, K., Hikasa, Y., Matsuda, H. (1999). IgE Hyperproduction Through Enhanced Tyrosine Phosphorylation of Janus Kinase 3 in NC/Nga Mice, a Model for Human Atopic Dermatitis. J. Immunol. 162: 1056-1063 [Abstract] [Full Text]  
• Hall, I P (1999). Genetics and pulmonary medicine bullet  8: Genetics and pulmonary medicine: asthma. Thorax 54: 65-69 [Full Text]  
• Haque, S. J., Harbor, P., Tabrizi, M., Yi, T., Williams, B. R. G. (1998). Protein-tyrosine Phosphatase Shp-1 Is a Negative Regulator of IL-4- and IL-13-dependent Signal Transduction. J. Biol. Chem. 273: 33893-33896 [Abstract] [Full Text]  
• Grünig, G., Warnock, M., Wakil, A. E., Venkayya, R., Brombacher, F., Rennick, D. M., Sheppard, D., Mohrs, M., Donaldson, D. D., Locksley, R. M., Corry, D. B. (1998). Requirement for IL-13 Independently of IL-4 in Experimental Asthma. Science 282: 2261-2263 [Abstract] [Full Text]  
• Ryan, J. J., DeSimone, S., Klisch, G., Shelburne, C., McReynolds, L. J., Han, K., Kovacs, R., Mirmonsef, P., Huff, T. F. (1998). IL-4 Inhibits Mouse Mast Cell Fc{epsilon}RI Expression Through a STAT6-Dependent Mechanism. J. Immunol. 161: 6915-6923 [Abstract] [Full Text]  
• Barnes, P. J., Chung, K. F., Page, C. P. (1998). Inflammatory Mediators of Asthma: An Update. Pharmacol. Rev. 50: 515-596 [Abstract] [Full Text]  
• Youn, J., Chen, J., Goenka, S., Aronica, M. A., Mora, A. L., Correa, V., Sheller, J. R., Boothby, M. (1998). In Vivo Function of an Interleukin 2 Receptor {beta} Chain (IL-2R{beta})/IL-4R{alpha} Cytokine Receptor Chimera Potentiates Allergic Airway Disease. JEM 188: 1803-1816 [Abstract] [Full Text]  
• Ryan, J. J., McReynolds, L. J., Huang, H., Nelms, K., Paul, W. E. (1998). Characterization of a Mobile Stat6 Activation Motif in the Human IL-4 Receptor. J. Immunol. 161: 1811-1821 [Abstract] [Full Text]  
• Altshuler, D., Kruglyak, L., Lander, E. (1998). Genetic Polymorphisms and Disease. NEJM 338: 1626-1626 [Full Text]  
• GASTON, J S H (1998). Will the increasing prevalence of atopy have a favourable impact on rheumatoid arthritis?. Ann Rheum Dis 57: 265-267 [Full Text]  
• Grimbacher, B., Holland, S. M., Puck, J. M., Hershey, G. K. K., Chatila, T. A. (1998). The Interleukin-4 Receptor Variant Q576R in Hyper-IgE Syndrome. NEJM 338: 1073-1074 [Full Text]  
• Rosenwasser, L. J. (1997). Interleukin-4 and the Genetics of Atopy. NEJM 337: 1766-1767 [Full Text]  
• Daniel, C., Salvekar, A., Schindler, U. (2000). A Gain-of-function Mutation in STAT6. J. Biol. Chem. 275: 14255-14259 [Abstract] [Full Text]