Abstracts S183 J ALLERGY CLIN IMMUNOL VOLUME 117, NUMBER 2 711 Enhanced Expression of Innate Immune Genes in Chronic Rhinosinusitis A. Q. Truong-Tran1, R. Kern2, D. Conley2, S. Retsema2, L. Grammer, III1, L. Suh1, J. Tirumalasetty1, B. Tancowny1, A. Tripathi1, R. Schleimer1; 1Allergy-Immunology, Northwestern University, Chicago, IL, 2Otolaryngology, Northwestern University, Chicago, IL. RATIONALE: Chronic rhinosinusitis (CRS) is an upper airway disease with increasing prevalence but poorly understood pathogenesis. Recent studies have identified inducible innate immune responses in airway epithelial cells. We hypothesized that altered expression of Toll like receptors (TLR), complement components and other antimicrobial genes may contribute to the pathogenesis of CRS. Normal subjects (NS) and patients with chronic rhinosinusitis (CRS) were studied to determine whether the expression of innate immune genes is perturbed in CRS. METHODS: 9 NS and 32 CRS patients were recruited with approved consent and epithelial cells collected from the inferior turbinate by scraping with a Rhinoprobe™. RNA was isolated using the RNeasy kit and samples analyzed for Deleted in mammalian brain tumor 1 (DMBT1), Chitinase-1, Complement factors C3, B and P, Secretory leukocyte protease inhibitor (SLPI), TLR 1-10 and Thymic stromal lymphopoietin (TSLP) by Taqman Real-Time PCR. RESULTS: Tissues from CRS patients had significantly increased expression of mRNA for Chitinase-1 (25 ± 1.6 fold, p=0.01), Factor P (28 ± 2 fold, p=0.02) and TLR-2 (7.6 ± 1.7 fold, p=0.002). Factor B (5.8 ± 2.2 fold), TSLP (4.5 ± 2.0 fold, p=0.06), and SLPI (1.8 ± 4.2 fold) were also increased, although statistical significance was not reached. Expression of DMBT1 and Complement C3 in CRS patients was not different compared to expression in NS patients. CONCLUSIONS: These data suggest that TLR-2, Chitinase-1, and Factor P are elevated in CRS and may reflect altered recognition of and response to invasive microbes in the nasal mucosa. 712 Total and Specific Nasal IgE to Dermatophagoides Pteronyssinus in Patients with Persistent Rhinitis C. Rondon1, S. Lopez2, R. R-Pena2, J. J. Romero1, T. D. Fernandez2, C. Antunez2, I. Dona1, M. S. Fuentes1, J. L. Rodriguez-Bada2, M. Blanca1; 1Allergy Service, Carlos Haya Hospital, Malaga, SPAIN, 2Research Laboratory, Carlos Haya Hospital, Malaga, SPAIN. RATIONALE: Allergic rhinitis is a high prevalent disease. Nasal provocation test with allergen (NPTA) is the diagnostic gold standard in these patients but it is not always feasible, because of the high number and the multi-sensitization of individuals affected. It is not unusual to find patients with typical symptoms of persistent allergic rhinitis (PER) with both skin prick-test (SPT) and specific-IgE negative; these patients are diagnosed clinically with persistent idiopathic non-allergic rhinitis (PINAR). We analyzed the presence of total and specific-IgE to Dermatophagoides pteronyssinus (DP), in nasal lavage from patients with PINAR, PER and healthy control subjects. METHODS: Fifty-two patients with symptomatic persistent rhinitis (24 patients with PER and 28 with PINAR) and 15 healthy controls were included. The presence of total and specific-IgE to DP was analyzed by nephelometry and immunoassay, respectively, in nasal lavage obtained using the modified Greiff-Grumberg method. Phenotype cell analysis was done by flow cytometry with different monoclonal antibodies (CD16FITC, CD8-FITC, CD4-PE, CD33-PE, CD3-PerCP, and CD45-APC). RESULTS: In the PINAR group, we found three patients with specificIgE to DP (10.71%). These patients showed a similar leukocyte-lymphocyte phenotype to the PER group (eosinophils 34%, neutrophils <10%, lymphocytes 0.7% of total leukocytes, and CD3+CD4+ 21% of total lymphocytes). CONCLUSIONS: The measurement of specific-IgE in nasal lavage fluid can be used to optimize the diagnosis of PER, especially in patients with both SPT and serum specific IgE negative. Further NPTA and studies of the characteristics of the exudate must be undertaken to determine the mechanisms involved in the production of rhinitis. Funding: FIS and Junta de Andalucia 713 A Genomewide Screen for Chronic Rhinosinusitis Genes Identifies a Locus on Chromosome 7q J. M. Pinto1, M. G. Hayes2, D. Schneider3, N. Phillips4, J. Hyuen4, N. J. Cox2, R. M. Naclerio1, C. Ober4; 1Section of Otolaryngology-Head and Neck Surgery, The University of Chicago, Chicago, IL, 2Section of Genetic Medicine, Department of Medicine and Department of Human Genetics, The University of Chicago, Chicago, IL, 3Departmenr of Human Genetics, The University of Chicago, Chicago, IL, 4Department of Human Genetics, The University of Chicago, Chicago, IL. RATIONALE: Chronic rhinosinusitis (CRS) is an important public health problem with substantial impact. Though its pathophysiology is multifactorial, the underlying molecular basis of chronic sinusitis needs additional investigation. We hypothesized that genetic variation may be one factor that affects this disease. This is supported by the observation of CRS in several inherited conditions, its association with nasal polyposis which in some forms may be inherited, and association studies of certain genetic polymorphisms in case-control studies. METHODS: Our studies were conducted in the Hutterites, a religious isolate that practices a communal lifestyle and shares common environmental exposures. This well-characterized population has been the subject of studies of the genetics of asthma/atopy for over 10 years. Using physical examination, medical interviews, and review of medical records, we identified 8 individuals with CRS out of 297 screened. A 60 member, 9 generation pedigree including all affected individuals was then constructed. A genome-wide screen for loci influencing susceptibility to CRS using 1113 genome-wide markers was completed using Simwalk 2.83. RESULTS: The largest linkage signal (P = 0.0023, equivalent to LOD=2.01) was on chromosome 7q31 (127.15 cM; 1-LOD support region: 115cM to 135cM) and included the CFTR locus. CONCLUSIONS: These results represent the first genome-wide screen for CRS and suggest that a locus on 7q31 influences disease susceptibility. This may be the CFTR gene itself or another locus within this 22 Mb region. Ultimately, understanding the genes involved in CRS may lead to improvements in the diagnosis and treatment of this disease. Funding: The University of Chicago SUNDAY EP1 were significantly reduced (p0.04) in the AS, as compared with NAS patients. CONCLUSIONS: The data are consistent with a possible role for PGE2 in mediating epithelial repair in rhinitis and asthma. Since PGE2 exerts a range of inhibitory actions on inflammatory leukocytes via the EP2 receptor, its reduced expression in AS rhinosinusitis may be partly responsible for the increased inflammatory infiltrate and production of cysteinyl leukotriene which characterises AS disease.