MMF-associated hypogammaglobulinemia and prolonged B lymphocyte depression as documented by serial immunophenotying in an adolescent with SLE is ...
S162 Abstracts
618
Assessment of Susceptibility to Pertussis in Individuals with Atopic Conditions Other Than Asthma N. E. Rigelman-Hedberg1, A. S. Hettinger2, L. R. Fink2, H. Kita3, R. Jacobson2, B. Yawn4, X. Li3, K. Bailey3, Y. J. Juhn2; 1Mayo Clinic College of Medicine, Rochester, MN, 2Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, 3Mayo Clinic, Rochester, MN, 4Department of Research, Olmsted Medical Center, Rochester, MN. RATIONALE: Recently we reported an increased risk of pertussis among individuals with asthma. Despite shared underlying immunologic mechanisms, it is unknown whether individuals with non-asthmatic atopic conditions also have an increased risk of pertussis. We assessed if individuals with non-asthmatic atopic conditions have an increased risk of developing pertussis compared to those without atopic conditions. METHODS: This study was designed as a population-based case-control study. In 2004 and 2005, there were 214 pertussis cases reported in Olmsted County, MN. For each case, we identified 2 birthday and gender matched controls from 5,537 patients who had a negative test for pertussis within the same month. We conducted comprehensive medical record review to ascertain atopic conditions by the physician diagnoses of Ôatopic dermatitis,Õ Ôeczema,Õ Ôallergic rhinitis,Õ and Ôhay fever.Õ A conditional logistic regression was fit to assess the impact of atopic status on the risk of pertussis. RESULTS: Thus far, we have enrolled 142 cases and their corresponding 284 controls. The median age and proportion of male pertussis cases were 13.9 years and 74 (52.1%), respectively. Of the 142 cases, 53 (37.4%) were found to have atopic conditions compared to 112 (39.4%) of the controls. An odds ratio for atopic condition in predicting the risk of pertussis was 0.91 (95% CI: 0.58-1.40, p value 5 0.66). CONCLUSIONS: Unlike individuals with asthma, individuals with nonasthmatic atopic conditions do not appear to have increased susceptibility to pertussis. This difference in susceptibility to pertussis between asthma and non-asthmatic atopic conditions deserves further research.
619
MONDAY
Tuberculosis Occurrence After Introducing Asthma Treatment: A Report Of Three Cases D. I. Kim1, M. Kim1, C. Park2; 1Department of Internal Medicine, Changwon Fatima Hospital, changwon, Republic of Korea, 2Department of Internal Medicine, Sungae Hospital, Seoul, Republic of Korea. INTRODUCTION: The relationship between bronchial asthma and tuberculosis (TB) has stimulated the greatest interest and most controversy. We report 3 subjects with TB after introducing asthma treatment. They have no active lesions in chest radiography at first. METHODS: Patients underwent a medical history, chest radiography, allergen skin-prick testing, total and specific IgE measurements, methacholine bronchial provocation test. sputum AFB stain, and sputum AFB culture. RESULTS: Two patients were atopic asthma and one patients was clinically diagnosed asthma. They present persistent wheezing (2 of 3) and unsatisfactory symptom control to appropriate management (1 of 3). We checked chest CT and these were suspicious of tuberculosis. Sputum AFB stains were positive in all cases and all cultures were of Mycobacterium tuberculosis species. We treated TB with anti-tuberculosis agents successfully and maintained management of asthma. CONCLUSIONS: Pulmonary or endobronchial TB should be considered in asthmatic patients who present persistent wheezing or unsatisfactory response to management, at least in which TB is prevalent.
J ALLERGY CLIN IMMUNOL FEBRUARY 2009
620
Effects of IGIV on Dendritic Cell (DC) Maturation and Function N. Wasserbauer1,2, C. Allen1,2, P. Shah1,2, M. Ballow1,2; 1 Women and Children’s Hospital of Buffalo, Buffalo, NY, 2SUNY Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY. RATIONALE: Our laboratory has previously shown that 10% liquid IGIV promoted DC maturation. We investigated if the properties of this IGIV preparation were unique to this formulation compared to other IGIV products. METHODS: Immature DCs were derived from IL-4 and GM-CSF induced peripheral blood monocytes (PBMC) IGIV (0.15 mM-Gamunex10%, Carimune NF and 5% Flebogamma DIF), or HSA (protein control) was added to cultures. Differentiation into immature DC was assayed using monoclonal antibodies: CD14, CD1a, CD40, CD83, CD80, CD86, HLADR. Endocytosis function was assayed by flow cytometry, and antigen processing by allogeneic T-cell responses. RESULTS: All IGIV preparations inhibited the expression of CD1a, a marker for immature DC, during the maturation process. Gamunex produced the highest expression of CD83 (p < 0.001, N 5 10), a marker for mature DC, and CD80, a co-receptor (p < 0.001, N 5 11). There were no differences in the % expression of CD86, HLA-DR or CD40. However, mean florescent intensity (MFI) increased in Gamunex cultures (p < 0.001) for these markers. There was little effect of Flebogamma or Carimune NF compared to media alone or HSA on endocytosis. There was a significant decrease in endocytosis function with Gamunex (p < 0.001, N 5 5). Gamunex treated immature DC promoted (p < 0.001, N 5 11) greater antigen presentation function. CONCLUSIONS: Gamunex induced more mature DCs with increased expression of CD83 and increased antigen presentation function in MLC, but decreased endocytosis function, a property of immature DC. These findings may indicate differences in immune modulatory properties among IGIV preparations.
621
Serial Immunphenotyping and Prolonged B cell Dysfunction in Systemic Lupus Erythematosus (SLE) Treated with Mycophenolate mofetil (MMF) R. M. Kandyil1, A. A. Kamdar2, R. Warren2, I. C. Hanson1,3; 1Section of Allergy and Immunology, Houston, TX, 2Section of Rheumatology, Houston, TX, 3Baylor College of Medicine, Texas Childrens Hospital, Houston, TX. RATIONALE: Mycophenolate mofetil (MMF) is an immunosuppressive agent that impacts B and T cell function. It is commonly used in solid organ transplantation and increasingly in the treatment of autoimmune disorders. MMF-associated hypogammaglobulinemia and prolonged B lymphocyte depression as documented by serial immunophenotying in an adolescent with SLE is outlined. METHODS: Chart review, Quantitative immunoglobulins, Serial lymphocyte phenotyping, T cell lymphoproliferative assay. RESULTS: 2 months after administration of MMF (50 mg/kg/day), impressive hypogammaglobulinemia was documented with IgG decreased from 1090 to 390 mg/dl. All other classes showed a similar reduction. MMF was discontinued. Further evaluation revealed reduced IgG specific vaccine response. Serial lymphocyte phenotyping demonstrated normal T and NK cell percents but nearly absent B cell markers (patient CD19 0-3% vs age-matched range 6-23%). In vitro T cell function was preserved and CD4 and CD8 markers remained stable. Absent peripheral blood B cell markers persisted for 12 months following MMF discontinuation. Ig replacement was required. During this period, there was no clinical evidence of SLE. Complement levels normalized, anti-ds dna antibody was not detectable while her corticosteroids were reduced (0.43 to 0.11 mg/kg/day). CONCLUSIONS: Transient hypogammaglobulinemia and modest decreases in B cell markers lasting 6-9 months have been described in solid organ recipients treated with MMF. Although hypogammaglobulinemia rarely can be associated with SLE activity, this data suggests MMF-associated prolonged B cell depression reflecting exaggerated immune apoptosis. Serial immune evaluation is warranted for patients with autoimmune disorders treated with MMF. Ig replacement may be required in the face of persistent hypogammaglobulinemia.
