- Email: [email protected]
372 IgE bearing dendritic cells: Evidence for a possible role in the pathogenesis of atopic eczema
371
A COMPARISONOF SKIN MAST CELL NUMBERS IN MASTOCYTOSIS VS. UNEXPLAINED ANAPHYLAXIVFLUSHING.
373
Margarita Ph.D. and Dean 0. Metcalfe, M.D., NIH, Bethesda, Marvland. it has been sugqested that patients with unexplained anaphiiaxis or unexplained flushing (UEA/UEF) have systemic mastocvtosis (SM). a proposal-said to-be supported by excels &st cell (MC) numbers in the skin of these individuals. To examine this hypothesis, we determined the number and distribution of MC in the skin of 9 normal subjects (NS), 9 patients with UEA/UEF, 6 with urticaria pigmentosa (UP), and 12 with SM. Skin biopsies of NS contained 38.4&4 MC/mm* and biopsies of patients with UEA/UEF contained 71.8*13 MC/mm*. Similar modest increases in MC numbers are observed in a number of skin conditions. In contrast, lesional biopsies of patients with UP contained 596.5+278 MC/mm* (p
372
=BEARING POBBIBLB
ROLE
DBNDRITIC CELLS. IN ~Piiii%iiNBBIB
EVIDENCE OF
RUSH VENDt,l IMMUNDTHERAPY(V.I.T.) : A ONF YEAR EQLI OW-UP STUDY OF P' ASHA AND AIUWN lNDw,Q I--. Ph. D.. Francol~ . t,M,D..AlainBraaudC1S,Marseille France We have previously reported (j.A.C.1 1987, 79, 174, abst) that rush VIT inducbd a dramatic increase in plasma histamine levels in venom-sensitive patients. Maximum increase occurred 3 hours after the beginning of this treatment at 60 ug of venom. These 11 patients recetved a booster injection (81) of 100 ug of venom each month for one year. During this year patients did not devolopped adverse reactions to insect stings or to BI. In this study we investigated
changes
in plasma
histamine
levels
and venom
induced histamine release (HR). Histamine was assa@ by a solid phase competitive RIA (Immunotech, Marseille, France). Atone year bloodwasdrawn before the Blandthan 10,20,30and 60 minafter. 10 mfnafterthelast 81 plasma histamine levels significantly increased (p
FOR A ATOPIC
374
ECZEEA, Thomas Bieber, M.D., Jbrg Prinz, M.D., Johannes Ring, M.D., Munich. Germany. Immunocytochemical and immunoelectron microscopical investigations have been performed on cryosections and epidermal cell suspensions from normal and lesional skin of patients with atopic eczema using a panel of monoclonal antibodies (moab) reacting with IgE molecules or IOT6 (anti-CDla) reacting with LC and the socalled indeterminaTe. cells (IC). Serum IgE was determined for each patient at the day of biopsy. Numerous IgE+ dendritic cells were found in the dermal infiltrate; in double labelling, some of them appeared to be also CDla+. In lesional skin of patients with normal IgE levels, no IgE+ dendritic cells could be demonstrated in the epidermis. In contrast, lesional epidermis, and not, uninvolved skin, of patients with high IgE levels (>300 W/ml) displayed IgE+ dendritic cells, scattered through the epithelium but mostly grouped in the areas of strong spongiosis or within vesicles. Double labelling studies as well as comparative enumeration suggest that there exist at least two subpopulations of epidermal dendritic cells: CDla+/IgEcells and CDla+/IgE+ cells. Immunoelectronmicroscopical investigations showed that the latter exibit Birbeck granules which are known to be specific for LC. In summary, our results suggest that epidermal LC could acquire IgE molecules on their surface during the development of eczematous lesions; the posslble regulatory role of IgE-bearing LC and IC in the generation of atopic eczema needs further investigations.
261
EFFICACY OF RUSH IMMUNOTHERAPY WITH GRASS OR MULTIPLE POLLEN SPECIES ASSESSED BY NASAL CHALLENGE. I.Chanal, J.Bousquet, B. Lebel, F.B.Michel, Montpellier,France. immunotherapy (RIT) is effective Rush in grass pollen allergy but its results with multiple pollens are equivocal. controlled study A double-blind placebo was carried out with 66 patients (12-43 yr) to compare the efficacy of RIT with orchard grass pollen (in grass pollen allergies) and 3 to 5 pollen species including orchard grass pollens in patients allergic to several species. Efficacy was assessed by nasal challenge with numb&s of orchard grass 5-fold . increasing arains (50-156,250). The positivity uollen of challeige was studiedby examining iymptomi and release rhinorrhea, sneezes) (blockage, of histamine (titrated by RIA, Immunotech, France) and PGD2 (titrated by EIA, CEA, France) in nasal secretions. All extracts were standardized (Stallergtines, RIT consisted in 8-12 injections in France). 2-4 days to reach the maintenance dose (5,000 BU) that was followed by 6 injections. Patients had a cumulative dose of 35,000 to 41,000 BU of orchard grass before nasal challenge. results of nasal challenge: m+/-sd grains grass pollen placebo 1.5442 2,232 (a) 69,175_+68,411 (b) active 3,086+ 7,286 mixed pollens placebo active 28.706?49.411 (cl pa/b
A COMPARISONOF SKIN MAST CELL NUMBERS IN MASTOCYTOSIS VS. UNEXPLAINED ANAPHYLAXIVFLUSHING.
373
Margarita Ph.D. and Dean 0. Metcalfe, M.D., NIH, Bethesda, Marvland. it has been sugqested that patients with unexplained anaphiiaxis or unexplained flushing (UEA/UEF) have systemic mastocvtosis (SM). a proposal-said to-be supported by excels &st cell (MC) numbers in the skin of these individuals. To examine this hypothesis, we determined the number and distribution of MC in the skin of 9 normal subjects (NS), 9 patients with UEA/UEF, 6 with urticaria pigmentosa (UP), and 12 with SM. Skin biopsies of NS contained 38.4&4 MC/mm* and biopsies of patients with UEA/UEF contained 71.8*13 MC/mm*. Similar modest increases in MC numbers are observed in a number of skin conditions. In contrast, lesional biopsies of patients with UP contained 596.5+278 MC/mm* (p
372
=BEARING POBBIBLB
ROLE
DBNDRITIC CELLS. IN ~Piiii%iiNBBIB
EVIDENCE OF
RUSH VENDt,l IMMUNDTHERAPY(V.I.T.) : A ONF YEAR EQLI OW-UP STUDY OF P' ASHA AND AIUWN lNDw,Q I--. Ph. D.. Francol~ . t,M,D..AlainBraaudC1S,Marseille France We have previously reported (j.A.C.1 1987, 79, 174, abst) that rush VIT inducbd a dramatic increase in plasma histamine levels in venom-sensitive patients. Maximum increase occurred 3 hours after the beginning of this treatment at 60 ug of venom. These 11 patients recetved a booster injection (81) of 100 ug of venom each month for one year. During this year patients did not devolopped adverse reactions to insect stings or to BI. In this study we investigated
changes
in plasma
histamine
levels
and venom
induced histamine release (HR). Histamine was assa@ by a solid phase competitive RIA (Immunotech, Marseille, France). Atone year bloodwasdrawn before the Blandthan 10,20,30and 60 minafter. 10 mfnafterthelast 81 plasma histamine levels significantly increased (p
FOR A ATOPIC
374
ECZEEA, Thomas Bieber, M.D., Jbrg Prinz, M.D., Johannes Ring, M.D., Munich. Germany. Immunocytochemical and immunoelectron microscopical investigations have been performed on cryosections and epidermal cell suspensions from normal and lesional skin of patients with atopic eczema using a panel of monoclonal antibodies (moab) reacting with IgE molecules or IOT6 (anti-CDla) reacting with LC and the socalled indeterminaTe. cells (IC). Serum IgE was determined for each patient at the day of biopsy. Numerous IgE+ dendritic cells were found in the dermal infiltrate; in double labelling, some of them appeared to be also CDla+. In lesional skin of patients with normal IgE levels, no IgE+ dendritic cells could be demonstrated in the epidermis. In contrast, lesional epidermis, and not, uninvolved skin, of patients with high IgE levels (>300 W/ml) displayed IgE+ dendritic cells, scattered through the epithelium but mostly grouped in the areas of strong spongiosis or within vesicles. Double labelling studies as well as comparative enumeration suggest that there exist at least two subpopulations of epidermal dendritic cells: CDla+/IgEcells and CDla+/IgE+ cells. Immunoelectronmicroscopical investigations showed that the latter exibit Birbeck granules which are known to be specific for LC. In summary, our results suggest that epidermal LC could acquire IgE molecules on their surface during the development of eczematous lesions; the posslble regulatory role of IgE-bearing LC and IC in the generation of atopic eczema needs further investigations.
261
EFFICACY OF RUSH IMMUNOTHERAPY WITH GRASS OR MULTIPLE POLLEN SPECIES ASSESSED BY NASAL CHALLENGE. I.Chanal, J.Bousquet, B. Lebel, F.B.Michel, Montpellier,France. immunotherapy (RIT) is effective Rush in grass pollen allergy but its results with multiple pollens are equivocal. controlled study A double-blind placebo was carried out with 66 patients (12-43 yr) to compare the efficacy of RIT with orchard grass pollen (in grass pollen allergies) and 3 to 5 pollen species including orchard grass pollens in patients allergic to several species. Efficacy was assessed by nasal challenge with numb&s of orchard grass 5-fold . increasing arains (50-156,250). The positivity uollen of challeige was studiedby examining iymptomi and release rhinorrhea, sneezes) (blockage, of histamine (titrated by RIA, Immunotech, France) and PGD2 (titrated by EIA, CEA, France) in nasal secretions. All extracts were standardized (Stallergtines, RIT consisted in 8-12 injections in France). 2-4 days to reach the maintenance dose (5,000 BU) that was followed by 6 injections. Patients had a cumulative dose of 35,000 to 41,000 BU of orchard grass before nasal challenge. results of nasal challenge: m+/-sd grains grass pollen placebo 1.5442 2,232 (a) 69,175_+68,411 (b) active 3,086+ 7,286 mixed pollens placebo active 28.706?49.411 (cl pa/b