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966 Assessment of autoimmunity in chronic urticaria patients
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965
966
Abstracts
J ALLERGY CLIN IMMUNOL JANUARY 1996
E O S I N O P H I L C A T I O N I C P R O T E I N IN A T O P I C DERMATITIS AND URTICARIA Montoro A_ Chivato T. Lamina IL .Baeza M. Zubeldia J, gubio M. Madrid, Spain. The aim of this study was to determine the concentrations of eosinophil cationic protein (ECP) in serum of patients with skin allergic diseases as atopic dermatitis (AD) and urticaria in order to evaluate their association with the clinical severity of the disease. Fourteen patients with AD (ages 1-40, 8 female, 6 male), 38 with urticaria (ages 1-63, 24 female, 14 male) and 12 controls (ages 10-20, 3 female, 9 male). ECP determination was performed using CAP FEIA (Pharmacia). Patients medicated with eorticosteroids in the previous 3 months were excluded, as well as those with inflammatory allergic diseases. AD patients were classified in accordance with Rajka-Hanifln scale in 2 groups, mild (5 individuals) and moderate-severe (9 individuals). Urticaria (acute, recurrent and chronic) patients were also divided into 2 groups, in acute exacerbation (19 patients) and asymptomatic (19 patients). Mean ECP level in controls was 3.734-1.21 pg/l . in AD was 24.564-16.70 ~tg/I (p<0.O01) and in urticaria was 17.844-9.72 lag/l (p<0.001). Mean for mild AD patients was 6.92a:2.75 pg/I and for moderatesevere was 34.21~:13.62 pg/l (p<0.001). For urticarias, in acute exacerbation mean was 20.684-11.14 ~tg/land in asymptomatic patients was 15.01±7.66 (p=0.075, non-significant). ECP level is high in allergic patients with skin diseases. In DA, there is a significant relation between serum ECP and the clinical score. In urticaria patients such a relation was not found.
967
Assessment of Autoimmunity in Chronic Urticaria Patients. L Ton~, PhD. G Balakrishnan,
968
M D , J KQchan. PhD. and A P Kanlan. MD. Division of Allergy, S U N Y - S t o n y Brook, H e a l t h Sciences Center, Stony Brook, NY and Hoffman-LaRoche, Nutley, NJ. W e have prospectively assessed the ability of sera obtained f r o m patients with c h r o n i c urticaria to release beta Hexosaminidase ([5-Hex) from rat basophil leukemia (RBL) cells transfected with the ¢~ subunit of the IgE receptor. Fifty patients and twenty control subjects were tested U s i n g 10% histamine release as significant, 38 urticaria patients with hives were positive while only 1 control was positive (p < 0.001). Isolation of patients' IgG corroborated this result indicating the presence of IgG anti FceO~. W e next wished to correlate this result with histamine release using h u m a n basophils as well as by autologous skin testing. 30 o f these urticaria samples were tested compared to 10 controls. 12 patients and 1 control subject were positive; eight patients had 40 - 100% histamine release. These eight samples were tested on basophils o f six different donors. All were positive although the sensitivity varied and was unrelated to atopic status. Autologous skin testing was positive in 1/3 of subjects, ie 10 o f 30. All of these were positive by RBL and h u m a n basophil secretion. The data indicate that a subpopulation of chronic urticaria patients may have an autoimmune etiology with a cutaneous inflammatory response initiated by mast cell degranulation.
Association of Reduced NF-ATp Binding at the IL-4 Promoter Element CLE0 and High IgE Levels in Severe Atopie Eczema. M Walehner MD, E A Wierengal PhD, M Meurer MD, P Kind MD, G Plewig MD, G Messer MD. Munich, Germany and Amsterdam, The Netherlands The search for genetic factors that may predispose people to atopic disease concentrates on proteins involved in the regulation of lgE, such as the cytokine interleukin-4 (IL-4). In patients with severe atopic eczema (AE) IL.,4 is elevated due to activation of the T helper (Th) type 2 lymphocyte response. In cloned human Th2 vs. Thl cells, we identified a differential DNA binding pattern at the recognition site CLE0, the conserved lympbokine element 0, of the IL--4gene promoter with a strong transient npregulation of NFATp binding in Thl cells after activation with anti-CD3/CD28. To investigate the in vivo relevance of these results, we analyzed protein extracts from PBMC of severe AE patients with strongly elevated IgE levels (3.000- 35.000 kU/l). Gel retardation assays indicated that, like in Th2 clones, the NF-ATp binding to IL-4 CLE0 in these extracts was strongly reduced, as compared to PBMC extracts from control donors. Thus, systemically reduced NF-ATp activity at the CLE0 element seems to be involved in the molecular dysregulation of IL-4 gene expression in atoplc eczema patients and, hence, is inversely related to ICE produetlon.
Ovomucoid-specific CD8 ÷ TH2-1ike Cell Lines in Atopic D e r m a t i t i s P a t i e n t s [AD] w i t h Egg Allergy. HA Sampson MD, J Rowe BA, PA Eigenmann MD. DYM Leun~ MD, PhD, SK Huang PhD, Baltimore, MD & Denver, CO Significant in vitro airborne and food allergen-induced lymphocyte proliferation has been demonstrated in both allergic patients [pts] and normal controls. In pts with allergic rhinitis and asthma, aeroallergen-specific memory CD4 + T cells were shown to produce excessive IL-5 & IL-4 compared to controls, which was associated with elevated IgE levels and eosinophil differentiation. Characterization of food allergen-specificT cell lines is very limited. This study was designed to determine whether similar phenotypes and cytokine profiles of allergenspecific T cells are generated in pts with AD and food allergy. Ovomucoid-specific T-cell lines were established from PBMCs of 10 pts with AD and egg allergy, 5 pts with egg allergy, and 2 controls. Flow cytometry using Mab was used for detection of T-cell markers and semi-quantitative RT-PCR for cytokine mRNA. [Median % CD + cells/group; * = p < .05] Patients Median: %CD4 ÷ %CD8 + IL-5 IL-4 egg allergic AD 32-~ 62-x ++ + egg allergic 69 * 31 * + control 99 . / 1-/ Ovomucoid-specific T-cell lines from egg allergic AD pts were predominantly CD8 + TH2-1ike cells. This is in distinct constrast to aeroallergen-specifie T-cell lines reported in previous studies and suggests a unique immunopathogenic mechanism in food allergic patients.
965
966
Abstracts
J ALLERGY CLIN IMMUNOL JANUARY 1996
E O S I N O P H I L C A T I O N I C P R O T E I N IN A T O P I C DERMATITIS AND URTICARIA Montoro A_ Chivato T. Lamina IL .Baeza M. Zubeldia J, gubio M. Madrid, Spain. The aim of this study was to determine the concentrations of eosinophil cationic protein (ECP) in serum of patients with skin allergic diseases as atopic dermatitis (AD) and urticaria in order to evaluate their association with the clinical severity of the disease. Fourteen patients with AD (ages 1-40, 8 female, 6 male), 38 with urticaria (ages 1-63, 24 female, 14 male) and 12 controls (ages 10-20, 3 female, 9 male). ECP determination was performed using CAP FEIA (Pharmacia). Patients medicated with eorticosteroids in the previous 3 months were excluded, as well as those with inflammatory allergic diseases. AD patients were classified in accordance with Rajka-Hanifln scale in 2 groups, mild (5 individuals) and moderate-severe (9 individuals). Urticaria (acute, recurrent and chronic) patients were also divided into 2 groups, in acute exacerbation (19 patients) and asymptomatic (19 patients). Mean ECP level in controls was 3.734-1.21 pg/l . in AD was 24.564-16.70 ~tg/I (p<0.O01) and in urticaria was 17.844-9.72 lag/l (p<0.001). Mean for mild AD patients was 6.92a:2.75 pg/I and for moderatesevere was 34.21~:13.62 pg/l (p<0.001). For urticarias, in acute exacerbation mean was 20.684-11.14 ~tg/land in asymptomatic patients was 15.01±7.66 (p=0.075, non-significant). ECP level is high in allergic patients with skin diseases. In DA, there is a significant relation between serum ECP and the clinical score. In urticaria patients such a relation was not found.
967
Assessment of Autoimmunity in Chronic Urticaria Patients. L Ton~, PhD. G Balakrishnan,
968
M D , J KQchan. PhD. and A P Kanlan. MD. Division of Allergy, S U N Y - S t o n y Brook, H e a l t h Sciences Center, Stony Brook, NY and Hoffman-LaRoche, Nutley, NJ. W e have prospectively assessed the ability of sera obtained f r o m patients with c h r o n i c urticaria to release beta Hexosaminidase ([5-Hex) from rat basophil leukemia (RBL) cells transfected with the ¢~ subunit of the IgE receptor. Fifty patients and twenty control subjects were tested U s i n g 10% histamine release as significant, 38 urticaria patients with hives were positive while only 1 control was positive (p < 0.001). Isolation of patients' IgG corroborated this result indicating the presence of IgG anti FceO~. W e next wished to correlate this result with histamine release using h u m a n basophils as well as by autologous skin testing. 30 o f these urticaria samples were tested compared to 10 controls. 12 patients and 1 control subject were positive; eight patients had 40 - 100% histamine release. These eight samples were tested on basophils o f six different donors. All were positive although the sensitivity varied and was unrelated to atopic status. Autologous skin testing was positive in 1/3 of subjects, ie 10 o f 30. All of these were positive by RBL and h u m a n basophil secretion. The data indicate that a subpopulation of chronic urticaria patients may have an autoimmune etiology with a cutaneous inflammatory response initiated by mast cell degranulation.
Association of Reduced NF-ATp Binding at the IL-4 Promoter Element CLE0 and High IgE Levels in Severe Atopie Eczema. M Walehner MD, E A Wierengal PhD, M Meurer MD, P Kind MD, G Plewig MD, G Messer MD. Munich, Germany and Amsterdam, The Netherlands The search for genetic factors that may predispose people to atopic disease concentrates on proteins involved in the regulation of lgE, such as the cytokine interleukin-4 (IL-4). In patients with severe atopic eczema (AE) IL.,4 is elevated due to activation of the T helper (Th) type 2 lymphocyte response. In cloned human Th2 vs. Thl cells, we identified a differential DNA binding pattern at the recognition site CLE0, the conserved lympbokine element 0, of the IL--4gene promoter with a strong transient npregulation of NFATp binding in Thl cells after activation with anti-CD3/CD28. To investigate the in vivo relevance of these results, we analyzed protein extracts from PBMC of severe AE patients with strongly elevated IgE levels (3.000- 35.000 kU/l). Gel retardation assays indicated that, like in Th2 clones, the NF-ATp binding to IL-4 CLE0 in these extracts was strongly reduced, as compared to PBMC extracts from control donors. Thus, systemically reduced NF-ATp activity at the CLE0 element seems to be involved in the molecular dysregulation of IL-4 gene expression in atoplc eczema patients and, hence, is inversely related to ICE produetlon.
Ovomucoid-specific CD8 ÷ TH2-1ike Cell Lines in Atopic D e r m a t i t i s P a t i e n t s [AD] w i t h Egg Allergy. HA Sampson MD, J Rowe BA, PA Eigenmann MD. DYM Leun~ MD, PhD, SK Huang PhD, Baltimore, MD & Denver, CO Significant in vitro airborne and food allergen-induced lymphocyte proliferation has been demonstrated in both allergic patients [pts] and normal controls. In pts with allergic rhinitis and asthma, aeroallergen-specific memory CD4 + T cells were shown to produce excessive IL-5 & IL-4 compared to controls, which was associated with elevated IgE levels and eosinophil differentiation. Characterization of food allergen-specificT cell lines is very limited. This study was designed to determine whether similar phenotypes and cytokine profiles of allergenspecific T cells are generated in pts with AD and food allergy. Ovomucoid-specific T-cell lines were established from PBMCs of 10 pts with AD and egg allergy, 5 pts with egg allergy, and 2 controls. Flow cytometry using Mab was used for detection of T-cell markers and semi-quantitative RT-PCR for cytokine mRNA. [Median % CD + cells/group; * = p < .05] Patients Median: %CD4 ÷ %CD8 + IL-5 IL-4 egg allergic AD 32-~ 62-x ++ + egg allergic 69 * 31 * + control 99 . / 1-/ Ovomucoid-specific T-cell lines from egg allergic AD pts were predominantly CD8 + TH2-1ike cells. This is in distinct constrast to aeroallergen-specifie T-cell lines reported in previous studies and suggests a unique immunopathogenic mechanism in food allergic patients.