Recurrent respiratory papillomatosis (RRP): Disease severity associates with enhanced TH2-like dendritic cell chemokine (DC-CK1) plasma expression

Recurrent Respiratory Papillomatosis (RRP): Disease Severity Associates With Enhanced TH2-Like Dendritic Cell Chemokine (DC-CK1) Plasma Expression D. W. Rosenthal1,2, H. Schmidtmayerova2, B. M. Steinberg3,2, J. A. Devoti1,2, L. Hatam1,2, A. Vambutas3,2, V. R. Bonagura1,2; 1Allergy/Immunology, Long Island Jewish Medical Center and Schneider Children’s Hospital, New Hyde Park, NY, 2North Shore-Long Island Jewish Institute for Medical Research, New Hyde Park and Manhasset, NY, 3Otolaryngology and Communicative Disorders, Long Island Jewish Medical Center, New Hyde Park, NY. RATIONALE: RRP is characterized by recurrent benign tumors of the respiratory tract, caused by infection with human papillomavirus (HPV). The immunologic mechanism(s) that govern disease variation in RRP, and the factors that predispose only a small group of HPV-exposed individuals to develop RRP, remain unresolved. We have recently reported that RRP is a TH2-like disease, with an imbalance of IL-10 vs. IFN, IL-12 and IL-18 expression. We hypothesized that dendritic cells play an important role in establishing this imbalance. To understand the in vivo role of dendritic cells in the modulation of T-cells in patients with RRP, we asked whether the immature dendritic cell chemokine, DC-CK1, is elevated in the plasma of RRP patients compared to controls. METHODS: Plasma was obtained from RRP patients with mild-moderate(n=4) and severe disease(n=7) and from controls(n=17), after informed consent. DC-CK1 plasma concentration was measured by ELISA (R&D Systems). The mean ±SE concentration of DC-CK1 was compared by a Kruskal-Wallis Test. Intra-subject variability in DC-CK1 expression was determined by multiple samples over a 3-month period from 3 subjects. RESULTS: The in vivo expression of DC-CK-1 was significantly increased in the plasma of RRP patients and correlated significantly with disease severity(p=0.013). Mean concentrations in controls(37.6±9.4ng/ml) differed from patients with mild/moderated(64.0±9.4ng/ml) and severe disease(78.2±14.1ng/ml). The variation in DC-CK1 levels in multiple specimens from the same subject was always <4%. CONCLUSIONS: Enhanced in vivo expression of DC-CK1, and the association with disease severity, supports the hypothesis that dendritic cells contribute to a TH2-like T-cell response via production of DC-CK1 in RRP patients. Funding: NIH

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Gammaglobulin Infusion Causing Headache—Can Sucrose Be the Culprit? D. Sun, I. Hussain, S. Odenwald, K. Wehmeier; Washington University School of Medicine/Barnes Jewish Hospital, Saint Louis, MO. RATIONALE: Headaches associated with intravenous gammaglobulin infusion (IVIG) are commonly reported. We examined patients who developed headaches after switching IVIG preparations. METHODS: We reviewed three patients in the Asthma and Allergy Center receiving IVIG from May 2001 to Sept 2004. 1) 42 year old woman with recurrent sinusitis and common variable immunodeficiency syndrome started brand-X 10% at infusion rate of 0.26 mg/kg/min. 2) 35 year old woman with chronic sinusitis, SLE, and

functional hypogammaglobulinemia started brand-Y 10% at 0.18 mg/kg/min. 3) 69 year old woman with chronic sinusitis, fibromyalgia, recurrent UTI, and functional hypogammaglobulinemia with IgG subclass 1, 2 deficiency started brand-Y 5% at 0.09 mg/kg/min. All patients switched to brand-Z 5% at 0.09 mg/kg/min in 2004 due to institution regulations. RESULTS: Patients had good response to either brand-X or -Y. After switching to brand-Z, all three developed acute onset headache that started within 1-4 hours during the infusion and lasted 1-3 days. This recurred despite pre-medication with acetaminophen, prednisone, diphenhydramine, and slowing the infusion rate. After switching back to brand -X and -Y, symptoms resolved. Review of the different formulations shows brand -X and -Y have 0 g of sucrose while brand-Z contains 1 gram sucrose per gram of immunoglobulin. IgA content of brand-X, -Y, -Z are 270 ug/ml, <3.7 ug/ml, and < 25 ug/ml, respectively. CONCLUSIONS: The development of headache with IVIG infusion is brand specific and may be related to sucrose but not IgA content of the preparation. Clinically, it may be advisable to switch brands before trying different pre-medication regimens. Funding: Washington University School of Medicine Hypogammaglobulinemia and Recurrent Stevens-Johnson Syndrome: A Case Report L. B. Moreno, B. Kaplan; North Shore-Long Island Jewish Health System, New Hyde Park, NY. RATIONALE: We report the case of a child with Common Variable Immunodeficiency (CVID)/hypogammaglobulinemia with a two-year history of recurrent erythema multiforme major/Stevens-Johnson syndrome (EM/SJS). METHODS: Our patient is a nine- year old male who initially presented with a two-year history of recurrent EM/SJS. An unusual feature of the SJS/EM outbreaks was an associated seasonal pattern, predominantly during the spring and fall. Episodes were not precipitated by herpetic infection, or medication. There was a single episode of serologically determined Mycoplasma pneumonia, followed by EM/SJS. Previous treatment has been unsuccessful with oral acyclovir and slow response to oral prednisone. RESULTS: Clinical evaluation (at time of outbreaks) revealed multiple blistering lesions involving lips, oral mucosa, and diffuse skin involvement. Initial evaluation revealed normal CBC, UA, TFTs, CRP; negative serology for celiac, pemphigoid, and pemphigus; negative Herpes I & II. Immune evaluation revealed normal immunoglobulins levels, normal T & B subsets with slightly decreased CD4/CD8 ratio. Recent immunologic evaluation revealed hypogammabulinemia (IgG 478, IgM 14, IgA normal), normal T & B cells, decreased CD4/CD8 ratio, normal mitogen proliferation studies, and non-protective titers to H. influenza. Of note, within one year, there was loss of reactivity of allergic skin prick testing to oak, maple, and cladosporium. This may be attributed to the evolving immunodeficiency. Since starting monthly IVIG replacement therapy, there have been no EM/SJS outbreaks. CONCLUSION: In summary, we report the case of a child with CVID with initial presentation of recurrent EM/SJS. To our knowledge, there are no reported cases of hypogammaglobulinemia/CVID presenting with recurrent EM/SJS.

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Abstracts S81

J ALLERGY CLIN IMMUNOL VOLUME 115, NUMBER 2