728 Late-Breaking Abstracts J ALLERGY CLIN IMMUNOL MARCH 2009 LB19 A Novel Autoinflammatory Disease Due to Homozygous Deletion of the IL-1RN locus; Effective Treatment with Recombinant IL-1 Receptor Antagonist J. Verbsky, S. Reddy, M. Suchi, U. Broeckel, M. Hessner; Medical Col- lege of Wisconsin, Milwaukee, WI. RATIONALE: We describe a novel auto-inflammatory disorder caused by deletion of IL-1 receptor antagonist, and compare this disorder to Neonatal Onset Multisystem Inflammatory Disorder (NOMID). METHODS: Genome-wide Single Nucleotide Polymorphism analysis was performed using the Affymetrix 6.0 array. Global gene expression patterns were performed using the GeneChip human genome U133 plus 2.0 array. Peripheral blood mononuclear cells (PBMCs) were stimulated with lipopolysaccharide and supernatants analyzed for cytokine expres- sion using the BD Cytometric Bead Array human inflammation kit or by an IL-1‚ ELISA. LPS stimulated or unstimulated PBMC were stained with antibodies to CD14 and analyzed by flow cytometry. RESULTS: We describe a patient with a novel auto-inflammatory disease characterized by pustular rash, systemic inflammation, marked osteope- nia, lytic bone lesions, respiratory failure and thromboses. Genetic studies showed a 175KB homozygous deletion at 2q13, which encompasses sev- eral IL-1 family members including the IL-1 receptor antagonist gene (IL- 1RN). Gene expression analysis and cytokine production from PBMCs demonstrate elevated production of inflammatory cytokines at baseline that increased after LPS stimulation. A similar increase was not observed in PBMCs from a patient with NOMID. Finally, monocytes from this patient were resistant to apoptosis, whereas monocytes from a patient with NOMID were susceptible. Importantly, treatment with recombinant IL-1 receptor antagonist resulted in complete resolution of symptoms. CONCLUSIONS: Deletions in the IL-1 locus encompassing IL-1 recep- tor antagonist results in an auto-inflammatory disorder with similarities to NOMID, but with severe osteopenia, lytic bone lesions, and a severe clin- ical course. Gene expression and cytokine analysis demonstrate important differences from NOMID. LB20 An Inactivating, Frame-shifted Mutation of ‚III Tryptase is Common in People of Northern and Western European Ancestory N. Trivedi, B. Tamraz, P. Y. Kwok, G. H. Caughey; UCSF, San Francisco, CA. RATIONALE: Mast cell tryptases are implicated in asthma. As part of an effort to understand contributions of tryptase genetic variation to asthma, we investigated prevalence and variability of the relatively unexplored ‚III subtype of tryptase genes. METHODS: We sequenced βIII genes and genotyped populations wide- ly varying in race/ethnicity. RESULTS: βIII tryptases are commonly inherited but prevalence varies strikingly between populations. At least one copy is present in 58% of a population with Northern/Western European ancestry (allele frequency 0.19) but in only 17% of Han Chinese (allele frequency 0.04). III genes, which can occupy the TPSB2 locus, are strongly linked with I genes, which can occupy the neighboring TPSAB1 locus. Thus, I and III are highly likely to be co-inherited. Mining of expressed sequence tag data- bases and sequencing of transcripts from mast cell lines detected a frame- shifted III variant. Like dysfunctional  tryptase, which is an allele at the TPSAB1 locus, frame-shifted III is likely inactive in that it lacks nearly half of the catalytic domain. Frame-shifted III is common in the European population, being present in 17% of screened individuals and comprising 22% of III alleles. CONCLUSIONS: Mast cell III tryptases are commonly inherited by individuals of European ancestry. They often are dysfunctional, but strong linkage to functional I genes greatly limits the likelihood of co-inherit- ing dysfunctional III and · tryptase genes on the same chromosome, RATIONALE: Non allergic rhinitis (NAR) is characterised by persistent nasal dysfunction with symptoms of rhinorrhoea and nasal congestion unrelated to allergy, infection or structural change. Neuronal mechanisms are thought to play an important role in nasal symptoms. To develop a strategy to study this disease, a preclinical guinea pig model of NAR was developed where neuronal stimulants such as capsaicin, hypertonic saline (HTS) and cold dry air (CDA) were unilaterally delivered intranasally. This produced a contralateral secretory response associated with the parasympathetic reflex and was quantified using MRI. METHODS: Guinea pigs (n=6/group) were intranasally sensitized with ovalbumin over 2 weeks. Urethane anaesthetised animals were placed in a 2T MRI scanner and basal scans of the nose were acquired. Animals were then challenged unilaterally with dose range of capsaicin (0.46, 4.6 and 15.25ug), HTS (3, 5 and 10%) or bilaterally with CDA. Following 10 minutes the animals were re-scanned and nasal fluid secretions and tissue engorgement were quantified. Separate groups of animals were pretreated with atropine at 1h prior to capsaicin or HTS challenge. RESULTS: Following both, capsaicin and hypertonic saline challenges, a dose dependent and significant increase (p<0.005) in contralateral fluid secretions was observed together with increases in nasal tissue swelling. Similarly an increase in bilateral fluid secretion was observed following delivery of CDA. In atropine pretreated animals the capsaicin and hyper- tonic responses were abolished. CONCLUSIONS: The in vivo MRI guinea pig model described pro- duces a robust and reproducible parasympathetic reflex response which may provide a platform for studying neuronal mechanism of rhinitis. LB18 Characteristics Associated with Premature Discontinua- tion of Allergen Immunotherapy among Children and Adults: Findings from a Large, Single-Specialty Allergy Practice in the United States D. Brown 1 , C. Hankin 2 , D. Scott 1 , M. Henry 1 , K. Anderson 1 , Z. Wang 2 ; 1 Allergy Partners, Asheville, NC, 2 BioMedEcon, Moss Beach, CA. RATIONALE: Although premature discontinuation of allergy immunotherapy (PDIT) is a common problem among patients receiving subcutaneous allergen immunotherapy (SCIT), little is know about patient- and system-related characteristics associated with likelihood for PDIT. METHODS: We conducted a six-year (6/6/2002 to 6/30/2008) retrospec- tive analysis of computerized claims from selected clinic sites within a large, single-specialty, allergy practice to examine characteristics associ- ated with likelihood of PDIT (>3 month gap between IT administrations within 2 years of initiation). Characteristics included patient sex, age at IT initiation, insurance (commercial, Medicaid, Medicare, other) and clinic site. Analyses were conducted separately for children (<18 years) and adults (>18 years). RESULTS: We identified 1,927 patients (840 children and 1087 adults) who received >1 IT administration and had >2 years of data following IT initiation. Rates of PDIT were 41% for children and 36% for adults. Compared to commercially insured children, those on Medicaid were 2.4 times more likely to prematurely discontinue IT (p<0.0001); sex, age at IT initiation, and clinic site did not significantly predict childhood PDIT. Compared to adult males, adult females were 1.4 times more likely to pre- maturely discontinue IT; younger adults (aged 18-29) were 2.4 times more likely to prematurely discontinue IT than those >50 years. Compared to commercially insured adults, those using “other” (e.g., VA, Champus) coverage were 59% less likely to prematurely discontinue IT. Site location did not significantly predict adult PDIT. CONCLUSIONS: Findings provide a benchmark for SCIT-related PDIT among children and adults, and describe patient and systems characteris- tics associated with the current likelihood for PDIT.