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671 Current etiological concepts of recurrent aphthous ulcers (RAU): A light, transmission and scanning electron microscopic study
S226
Abstracts
670 HLA
Involvement in CDS+ Cell-Mediated Suppression of HIV C Muckewicz, J Levy University of California San’ Francisco, San Francisco, CA CDS+ cells from HIV-infected individuals can suppress HIV replication in cultured CD4+ cells by a noncytolytic mechanism. Maximal suppressive activity occurs when the CDS+ cells and the infected CD4+ target cells are syngeneic; however, complete inhibition of virus replication is achieved even if the CDS+ cells and the CD4+ cells are HLA mismatched. The objective of this study was to directly assess the requirement of HLA class I and class II for efficient suppression of HIV by antiviral CDS+ cells. The human Blymphoblastoid cell line .22 I does not express HLA-A, HLA-B, or HLA-C class I antigens, but does express the class II antigens HLADR. HLA-DQ, and HLA-DP. Culturing HIV-infected .221 cells with CDS+ cells purified from HLA-unrelated HIV-infected individuals resulted in 50-80% reduction in HIV replication. CDS+ cells from uninfected individuals did not appreciably affect HIV replication. Flow cytometry revealed that the antiviral CDS+ cells did not reduce the number of ,221 cells in culture, relative to the cocultures with CDS+ cells from uninfected individuals. The results indicate that recognition of the major HLA class I molecules is not necessary for CDS+ cell-mediated suppression of HIV replication, neither in an HIV antigen- nor alloantigen-specific manner. We are currently examining .221 variant cell lines that do not express HLA class II molecules to rule out possible allogeneic activity to these antigens. The results of this study suggest that the mediation of this type of antiviral response does not involve classical HLA-antigen recognition at the effector stage.
671 Current
Etiological Concepts of Recurrent Aphthous Ulcers (RAU): A Light, ‘Dsnsmission and Scanning Electron Microscopic Study M Aboul-Khair*, H Alyf. K Guindy# *Al Azhar University tAin Shams University $El Minia University Recurrent aphthous ulcers @AU) are disorders characterized by recurring ulcers localized to the oral mucosa affecting 17-20% worldwide. The exact etiology of such ulcers is a subject of controversy. Immunological abnormalities are growing new concept in the development of such ulcers. Up to date detailed ultrastructural changes during ulcer development and its healing are not existing. The present study investigated uhrastructurally the RAU during its active and healing phases with special emphasis to its correlation with the possible variable etiological factors. Eighteen Egyptian patients were included in the present study. Detailed light, transmission and scanning electron microscopic examination of the excised RAU were performed. The epithelium over RAU area showed de-epitbelization and extensive polymorphs and mononuclear infiltrates together with corial perivasculitis. An extensive increase in the number of mast cells was seen with evidence of their degranulation. The loss of adhesion between epithelial cell keratinocytes as well as their attachment to their basal lamina seen in RAU was taken as an indication of delayed type hypersensitivity or cell mediated response to an antigenic stimulus residing within the epithelium. The existence of mononuclear cell infiltrates both epithelial and perivascular, intracellular oedema and graded epitheha1 cell changes are supporting the notion of delayed type hypersensitivity as a possible etiologic factor in RAU development. Early
J ALLERGY CLIN IMMUNOL JANUARY 2000
extravasation of erythrocytes and infiltration of neutrophils observed in the present study constitute a phenomenon of immunecomplex vasculitis. Surprisingly, active fungal association was detected during active ulceration. Such fungal involvement may account for recurrence of aphthous ulcers. Moreover intranuclear inclusion bodies similar to viral inclusions were noticed within the surface epithelial cell near the ulcer edge. During the healing phase of RAU, a noticeable tibroblastic proliferation with basal cell mitosis was revealed. In conclusion, the present study was able to document for the first time the different spatial or temporal ultrastructural changes that occur during an active and healing phases of RAU. We provide a direct evidence for possible role of fungal association whether it is a primary or merely secondary, together with other immunological and viral involvement in the development of such ulcers.
672 Pharmacokinetic
Evaluation of a Vapor-Heated Cl-Inhibitor Concentrate AT Waytes*. B Peak*. W Eng1.f. N Wappler*, FS Rosenf *Baxter Hyland Immuno, Rochester, MI tCenter for Blood Research, Boston, MA $Baxter AG, Vienna, Austria Hereditary Angioedema (HAE), which results from a genetic deficiency of Cl-inhibitor (Cl-INH), is characterized by episodic bouts of edema, which can become life threatening. Replacement therapy with concentrates of Cl -1NH has been used to stop the progression of attacks of edema, and also to prevent attacks. To evaluate the recovery and half-life of a vapor-heated Cl-INH concentrate, infusions of approximately 25 plasma units/kg body weight were administered to 15 asymptomatic HAE patients. One plasma unit (P.U.) is equivalent to the Cl-INH activity present in one ml of fresh normal human plasma. Blood was drawn for the determination of functional and antigenic Cl-INH levels, and antigenic C4 levels at pre-infusion. and at 15 and 30 minutes, and 1,2,4,8,12,16,24,48,96, and 144 hours, post infusion. Functional Cl-INH was determined using a calorimetric enzymatic assay. Antigenic C I -1NH and C4 were determined by RID. The mean preinfusion level of functional Cl-INH was 20.2% normal (SD=9.58). and rose to a peak level of 86.2% (SD=l2.51) by the I5 minute determination. The mean pre-infusion level of antigenic Cl-INH was 5.99 mg/dl (SD=3.32) and rose to a peak level of 24.9 mg/dl (SD=5.28) by the 15 minute determination. The mean functional half-life of Cl-INH was 50.08 hours (SD=S.SO), compared to 37.94 hours (SD=9.77) for antigenic Cl-INH. The mean in vivo recovery (corrected for plasma volume) was determined to be 107.8% for functional Cl-INH and 148.2% for antigenic Cl-INH. The mean pre-infusion C4 level was 8.21 mg/dl (SD=3.84). Following ClINH infusion, a significant increase in C4 levels was seen within 8 to 16 hours, reaching a peak of 14.09 mg/dl (SD=5.79) by the 48 hour determination.
673 Allergenicity
of Spider Mites Such as Citrus Red Mite, European Red Mite, and Two-Spotted Spider Mite, and its CrossReactivity With Domestic Mites Sang-Heon Cho*f, Yoon-Keun Kim*f, Soo-Yeon Leef, Kyung-Up Min*f. You-Young Kim*7 *Department of Internal Medicine, Seoul National University College of Medicine tInstitute of Allergy and Clinical Immunology, Seoul National University Medical Research Center BACKGROUND: Recent surveys have demonstrated that spider mites (Family Tetranychidae) such as citrus red mite (Panonythus citri. CRM), European red mite (Panonychus ulmi, ERM) and
Abstracts
670 HLA
Involvement in CDS+ Cell-Mediated Suppression of HIV C Muckewicz, J Levy University of California San’ Francisco, San Francisco, CA CDS+ cells from HIV-infected individuals can suppress HIV replication in cultured CD4+ cells by a noncytolytic mechanism. Maximal suppressive activity occurs when the CDS+ cells and the infected CD4+ target cells are syngeneic; however, complete inhibition of virus replication is achieved even if the CDS+ cells and the CD4+ cells are HLA mismatched. The objective of this study was to directly assess the requirement of HLA class I and class II for efficient suppression of HIV by antiviral CDS+ cells. The human Blymphoblastoid cell line .22 I does not express HLA-A, HLA-B, or HLA-C class I antigens, but does express the class II antigens HLADR. HLA-DQ, and HLA-DP. Culturing HIV-infected .221 cells with CDS+ cells purified from HLA-unrelated HIV-infected individuals resulted in 50-80% reduction in HIV replication. CDS+ cells from uninfected individuals did not appreciably affect HIV replication. Flow cytometry revealed that the antiviral CDS+ cells did not reduce the number of ,221 cells in culture, relative to the cocultures with CDS+ cells from uninfected individuals. The results indicate that recognition of the major HLA class I molecules is not necessary for CDS+ cell-mediated suppression of HIV replication, neither in an HIV antigen- nor alloantigen-specific manner. We are currently examining .221 variant cell lines that do not express HLA class II molecules to rule out possible allogeneic activity to these antigens. The results of this study suggest that the mediation of this type of antiviral response does not involve classical HLA-antigen recognition at the effector stage.
671 Current
Etiological Concepts of Recurrent Aphthous Ulcers (RAU): A Light, ‘Dsnsmission and Scanning Electron Microscopic Study M Aboul-Khair*, H Alyf. K Guindy# *Al Azhar University tAin Shams University $El Minia University Recurrent aphthous ulcers @AU) are disorders characterized by recurring ulcers localized to the oral mucosa affecting 17-20% worldwide. The exact etiology of such ulcers is a subject of controversy. Immunological abnormalities are growing new concept in the development of such ulcers. Up to date detailed ultrastructural changes during ulcer development and its healing are not existing. The present study investigated uhrastructurally the RAU during its active and healing phases with special emphasis to its correlation with the possible variable etiological factors. Eighteen Egyptian patients were included in the present study. Detailed light, transmission and scanning electron microscopic examination of the excised RAU were performed. The epithelium over RAU area showed de-epitbelization and extensive polymorphs and mononuclear infiltrates together with corial perivasculitis. An extensive increase in the number of mast cells was seen with evidence of their degranulation. The loss of adhesion between epithelial cell keratinocytes as well as their attachment to their basal lamina seen in RAU was taken as an indication of delayed type hypersensitivity or cell mediated response to an antigenic stimulus residing within the epithelium. The existence of mononuclear cell infiltrates both epithelial and perivascular, intracellular oedema and graded epitheha1 cell changes are supporting the notion of delayed type hypersensitivity as a possible etiologic factor in RAU development. Early
J ALLERGY CLIN IMMUNOL JANUARY 2000
extravasation of erythrocytes and infiltration of neutrophils observed in the present study constitute a phenomenon of immunecomplex vasculitis. Surprisingly, active fungal association was detected during active ulceration. Such fungal involvement may account for recurrence of aphthous ulcers. Moreover intranuclear inclusion bodies similar to viral inclusions were noticed within the surface epithelial cell near the ulcer edge. During the healing phase of RAU, a noticeable tibroblastic proliferation with basal cell mitosis was revealed. In conclusion, the present study was able to document for the first time the different spatial or temporal ultrastructural changes that occur during an active and healing phases of RAU. We provide a direct evidence for possible role of fungal association whether it is a primary or merely secondary, together with other immunological and viral involvement in the development of such ulcers.
672 Pharmacokinetic
Evaluation of a Vapor-Heated Cl-Inhibitor Concentrate AT Waytes*. B Peak*. W Eng1.f. N Wappler*, FS Rosenf *Baxter Hyland Immuno, Rochester, MI tCenter for Blood Research, Boston, MA $Baxter AG, Vienna, Austria Hereditary Angioedema (HAE), which results from a genetic deficiency of Cl-inhibitor (Cl-INH), is characterized by episodic bouts of edema, which can become life threatening. Replacement therapy with concentrates of Cl -1NH has been used to stop the progression of attacks of edema, and also to prevent attacks. To evaluate the recovery and half-life of a vapor-heated Cl-INH concentrate, infusions of approximately 25 plasma units/kg body weight were administered to 15 asymptomatic HAE patients. One plasma unit (P.U.) is equivalent to the Cl-INH activity present in one ml of fresh normal human plasma. Blood was drawn for the determination of functional and antigenic Cl-INH levels, and antigenic C4 levels at pre-infusion. and at 15 and 30 minutes, and 1,2,4,8,12,16,24,48,96, and 144 hours, post infusion. Functional Cl-INH was determined using a calorimetric enzymatic assay. Antigenic C I -1NH and C4 were determined by RID. The mean preinfusion level of functional Cl-INH was 20.2% normal (SD=9.58). and rose to a peak level of 86.2% (SD=l2.51) by the I5 minute determination. The mean pre-infusion level of antigenic Cl-INH was 5.99 mg/dl (SD=3.32) and rose to a peak level of 24.9 mg/dl (SD=5.28) by the 15 minute determination. The mean functional half-life of Cl-INH was 50.08 hours (SD=S.SO), compared to 37.94 hours (SD=9.77) for antigenic Cl-INH. The mean in vivo recovery (corrected for plasma volume) was determined to be 107.8% for functional Cl-INH and 148.2% for antigenic Cl-INH. The mean pre-infusion C4 level was 8.21 mg/dl (SD=3.84). Following ClINH infusion, a significant increase in C4 levels was seen within 8 to 16 hours, reaching a peak of 14.09 mg/dl (SD=5.79) by the 48 hour determination.
673 Allergenicity
of Spider Mites Such as Citrus Red Mite, European Red Mite, and Two-Spotted Spider Mite, and its CrossReactivity With Domestic Mites Sang-Heon Cho*f, Yoon-Keun Kim*f, Soo-Yeon Leef, Kyung-Up Min*f. You-Young Kim*7 *Department of Internal Medicine, Seoul National University College of Medicine tInstitute of Allergy and Clinical Immunology, Seoul National University Medical Research Center BACKGROUND: Recent surveys have demonstrated that spider mites (Family Tetranychidae) such as citrus red mite (Panonythus citri. CRM), European red mite (Panonychus ulmi, ERM) and