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ZongYao Wang,1 John S Sundy,1 Catherine M Foss,1 Huiman X Barnhart,2 Scott M Palmer,1 Sallie D Allgood,3 Evan Trudeau,1 Katie M Alexander,3 Marc C Levesque31Division of Pulmonary, Allergy and Critical Care Medicine, 2Duke Clinical Research Institute, 3Division of Rheumatology and Immunology, Duke University Medical Center, Durham, NC, USABackground: The CD14 C-159T single nucleotide polymorphism (SNP) has been investigated widely as a candidate genetic locus in patients with allergic disease. There are conflicting results for the association of the CD14 C-159T SNP with total serum immunoglobulin E (IgE) levels and atopy. There are limited data regarding the association of the CD14 C-159T SNP in subjects of African ancestry. The aim of the study was to determine whether the C-159T SNP and other CD14 SNPs (C1188G, C1341T) were associated with total serum IgE levels and with allergy skin test results in nonatopic and atopic subjects; as well as in Caucasian and African American subjects.Methods: A total of 291 participants, 18–40 years old, were screened to determine whether they were atopic and/or asthmatic. Analyses were performed to determine the association between CD14 C-159T, C1188G, or C1341T genotypes with serum IgE levels and with the number of positive skin tests among Caucasian or African American subjects.Results: We found no significant association of serum total IgE level with CD14 C-159T, C1188G, or C1341T genotypes within nonatopic or atopic subjects. Subjects with CD14-159 T alleles had significantly more positive allergen skin tests than subjects without CD14-159 T alleles (P = 0.0388). There was a significant association between the CD14 1188 G allele, but not the CD14 1341 T allele, with the number of positive skin-test results in Caucasians, but not in African Americans.Conclusion: These results support a possible association between CD14 polymorphisms and atopy. CD14-159 T or CD14 1188 G alleles were associated with atopic disease. For subjects with CD14 1188 G alleles, the association with atopic disease was stronger in Caucasians compared to African Americans.Keywords: total serum immunoglobulin E, IgE, skin prick test, SPT, CD14-159T, single nucleotide polymorphism, SNP, lipopolysaccharide, LPS, endotoxin

Context: Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need.Objective: To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout.Design, Setting, and Patients: Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406.Intervention: Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group).Main Outcome Measure: Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6.Results: In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008).Conclusion: Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo.Trial Registration: clinicaltrials.gov Identifier: NCT00325195. [ABSTRACT FROM AUTHOR]

It is not uncommon for nonallergy specialists to encounter patients with urticaria, angioedema, or complaints ofrecurring infections. Most cases of acute urticaria are self-limited and require only symptomatic treatment. Most chronic urticaria is idiopathic, although recent evidence suggests that about 40% of patients with chronic idiopathic urticaria have autoantibodies against the IgE receptor. Angioedema may occur in conjunction with or independent of urticaria. IgA deficiency and common variable immunodeficiency are primary immunodeficiencies that can present in adulthood, often with autoimmune manifestations. Knowledge of these allergy and immunology disorders leads to improved patient care through early recognition, appropriate initial evaluation and, when warranted, referral to an allergyand immunology specialist. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the efficacy of pegloticase in achieving and maintaining plasma urate levels of <6 mg/dl in gout patients in whom other treatments have failed, and to assess the pharmacokinetics and safety of pegloticase. METHODS: Forty-one patients were randomized to undergo 12-14 weeks of treatment with pegloticase at 1 of 4 dosage levels: 4 mg every 2 weeks, 8 mg every 2 weeks, 8 mg every 4 weeks, or 12 mg every 4 weeks. Plasma uricase activity, plasma urate, and antipegloticase antibodies were measured, pharmacokinetic parameters were assessed, and adverse events were recorded. RESULTS: The mean plasma urate level was reduced to

Early treatment with disease-modifying anti-rheumatic drugs (DMARDs) -- alone or in combination--can prevent joint damage and minimize disability. Until recently, the DMARDs used predominantly in patients with rheumatoid arthritis had been methotrexate, sulfasalazine, and hydoxychloroquine. Older DMARDs such as gold, D-penicillamine, and azathioprine have fallen out of favor because of their long-term toxicities or modest benefit. Six newer DMARDs - Ieflunomide, etanercept, infliximab, adalimumab, rituximab, and anakinra--have greatly expanded the current treatment options. [ABSTRACT FROM AUTHOR]