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Macrophage Activation Syndrome after Hematopoietic Cell Transplantation
Abstracts S205
J ALLERGY CLIN IMMUNOL VOLUME 117, NUMBER 2
Atopy as a Predictor of Favorable Response to Treatment with Interferon-Alpha in Patients with Chronic Hepatitis B M. R. Pijak1, F. Gazdik2, E. Jahnova2; 1Department of Internal Medicine, University Hospital, Bratislava, SLOVAKIA, 2Slovak Medical University, Bratislava, SLOVAKIA. RATIONALE: Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) is considered to be associated with a Th2 immune response, while HBeAg-negative CHB with a Th1 response. We aimed to determine whether the presence of atopy might influence HBeAg/antiHBe status and outcome of antiviral therapy. METHODS: We studied 73 treatment-naive patients with chronic hepatitis B, 39 men and 34 women aged 16-60 years (mean 32 years) with a positive HBV-DNA assay (Digene). Serological markers HBeAg and anti-HBe were tested by ELISA (MONOLISA, Sanofi Pasteur. The atopic status was determined on the basis of 2 or more positive skin prick tests from a panel consisting of 7 aeroallergens. After baseline evaluation all patients were treated with interferon-alpha (IFN) 10 MIU thrice weekly for 24 and 48 wks respectively, depending on HBeAg status. RESULTS: The prevalence of atopy in the entire cohort was 34 %. In the subgroup of HBeAg-positive patients the prevalence of atopy was significantly higher than in the HBeAg-negative patients (61.5% vs. 2.9 %, p< 0.0001, Chi-square test). One year after completion of the treatment, HBV-DNA was undetectable in 32.8 % of all patients. The proportion of responders was significantly higher among atopic patients than in nonatopic patients (52 % vs 22.9 %, p=0.012, Chi-square test). CONCLUSIONS: Consistently with the Th1/Th2 paradigm, we observed that patients with atopy have predominantly HBeAg-positive type CHB
790
and more favorable response to IFN. These results support the notion that both strong Thl activity and synchronous co-stimulatory Th2 activity may be required for a successful HBV elimination. Macrophage Activation Syndrome after Hematopoietic Cell Transplantation A. Sreedharan; Medicine, Indiana University School of Medicine, Indianapolis, IN. RATIONALE: Since a number of inflammatory conditions may occur during hematopoietic cell transplantation (HCT), elucidating the distinguishing features is important because treatments differ. We present a rare case of macrophage activation syndrome (MAS) that occurred following autologous HCT. METHODS: Serial physical examinations, standard laboratory evaluations and measurements of serum ferritin levels were recorded and a thorough literature review was compiled. RESULTS: A single patient with systemic juvenile rheumatoid arthritis experienced MAS in the post-transplant period. This condition was differentiated from other systematic post-transplant inflammatory conditions, including disseminated intravascular coagulation, engraftment syndrome and capillary leak. Extreme hyperferritinemia (> 150,000 ng/mL) was a distinguishing feature. The patient responded to combination glucocorticosteroids, IVIG and cyclosporine A. CONCLUSIONS: MAS occurs rarely after HCT, and is characterized by severe systemic inflammation and elevated serum ferritin. Early recognition and treatment may lead to a favorable outcome. Funding: Indiana Univsersity School of Medicine
791
Assessment of Histamine Release and Immunomodulation Induced by Restorative Dental Materials A. A. Babakhin1, A. I. Volozhin2, L. N. Kazarina2, O. O. Guschina2, J. A. Babakhina2, L. M. DuBuske3; 1National Research Center - Institute of Immunology, Ministry of Health of Russia, Moscow, RUSSIAN FEDERATION, 2Moscow Medical and Dental University, Moscow, RUSSIAN FEDERATION, 3Immunology Research Institute of New England, Gardner, MA. RATIONALE: Dental materials (DM) may modulate immune response. METHODS: DM Prizmafil (P), FiltekTM Z250 (F) and XRV Herculite Prodigy (H) were placed subcutaneously in (CBAxC57Bl/6)F1 mice (500 mg/mouse) one week before, simultaneously with or one week after immunization using 10 g/mouse of ovalbumin (OA). Anti-OA IgE and IgG antibodies were detected by passive cutaneous anaphylaxis and ELISA respectively. DM were pulverized and incubated in PIPES buffer at 37 C for 48 h, separated by centrifugation and supernatants (SNs) were assessed for leukocyte histamine release. RESULTS: Mice treated with P and H before or simultaneously with primary immunization had lower levels of anti-OA IgE than control. Mice treated with F had increased levels of anti-OA IgE. After the second and third immunizations, mice treated with P and H before immunization had lower levels of anti-OA IgG compared with control mice. When P, F and H were given either simultaneously or one week after primary immunization, levels of anti-OA IgG were greater than control. SN from F demonstrated significant HR while SN from P and H induced HR comparable to control. CONCLUSIONS: Dental materials may alter IgE and IgG responses to allergen and release histamine from blood basophils. Funding: IRINE and National Research Center – Institute of Immunology
792
MONDAY
Inhibition of Indoleamine 2,3-Dioxygenase does not Impede Oral Tolerance C. C. Bowman, M. J. DeVito, D. G. Ross, M. J. K. Selgrade; NHEERL, USEPA, Research Triangle Park, NC. RATIONALE: Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolizing enzyme, regulates immune tolerance through inhibition of T-cell proliferation. Pharmacologic inhibition of IDO, which causes fetal rejection and increased tumor resistance in mice, may prove useful in cancer treatment. IDO’s role in tolerance and high levels of expression in the intestine led us to hypothesize that it may function to maintain oral tolerance. METHODS: Initial pharmacokinetic studies were done to achieve relevant levels of the IDO inhibitor 1-methyl-tryptophan (1-MT) during antigen presentation. C3H/HeJ mice were orally treated with 750 mg/kg of 1-MT, a dose previously shown to enhance tumor rejection, and concurrently exposed to a tolerizing dose of ovalbumin (OVA). Experimental groups consisted of: vehicle, 1-MT, vehicle/OVA, or 1-MT/OVA. Following systemic immunization of all groups with OVA and alum, OVA-specific serum IgG and IgE were measured. RESULTS: Concomitant exposure to OVA and 1-MT did not enhance the subsequent immune response to OVA. Levels of OVA-specific antibody in animals with prior oral exposure to the antigen were reduced by at least half relative to those observed in animals with no prior exposure, regardless of inhibition of IDO. CONCLUSIONS: Transient inhibition of IDO at the time of oral antigen exposure does not prevent induction of oral tolerance. 1-MT does not function as an oral adjuvant under these experimental conditions, and appears unlikely to increase the risk of food allergy. (This abstract does not reflect EPA policy.)
789
J ALLERGY CLIN IMMUNOL VOLUME 117, NUMBER 2
Atopy as a Predictor of Favorable Response to Treatment with Interferon-Alpha in Patients with Chronic Hepatitis B M. R. Pijak1, F. Gazdik2, E. Jahnova2; 1Department of Internal Medicine, University Hospital, Bratislava, SLOVAKIA, 2Slovak Medical University, Bratislava, SLOVAKIA. RATIONALE: Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) is considered to be associated with a Th2 immune response, while HBeAg-negative CHB with a Th1 response. We aimed to determine whether the presence of atopy might influence HBeAg/antiHBe status and outcome of antiviral therapy. METHODS: We studied 73 treatment-naive patients with chronic hepatitis B, 39 men and 34 women aged 16-60 years (mean 32 years) with a positive HBV-DNA assay (Digene). Serological markers HBeAg and anti-HBe were tested by ELISA (MONOLISA, Sanofi Pasteur. The atopic status was determined on the basis of 2 or more positive skin prick tests from a panel consisting of 7 aeroallergens. After baseline evaluation all patients were treated with interferon-alpha (IFN) 10 MIU thrice weekly for 24 and 48 wks respectively, depending on HBeAg status. RESULTS: The prevalence of atopy in the entire cohort was 34 %. In the subgroup of HBeAg-positive patients the prevalence of atopy was significantly higher than in the HBeAg-negative patients (61.5% vs. 2.9 %, p< 0.0001, Chi-square test). One year after completion of the treatment, HBV-DNA was undetectable in 32.8 % of all patients. The proportion of responders was significantly higher among atopic patients than in nonatopic patients (52 % vs 22.9 %, p=0.012, Chi-square test). CONCLUSIONS: Consistently with the Th1/Th2 paradigm, we observed that patients with atopy have predominantly HBeAg-positive type CHB
790
and more favorable response to IFN. These results support the notion that both strong Thl activity and synchronous co-stimulatory Th2 activity may be required for a successful HBV elimination. Macrophage Activation Syndrome after Hematopoietic Cell Transplantation A. Sreedharan; Medicine, Indiana University School of Medicine, Indianapolis, IN. RATIONALE: Since a number of inflammatory conditions may occur during hematopoietic cell transplantation (HCT), elucidating the distinguishing features is important because treatments differ. We present a rare case of macrophage activation syndrome (MAS) that occurred following autologous HCT. METHODS: Serial physical examinations, standard laboratory evaluations and measurements of serum ferritin levels were recorded and a thorough literature review was compiled. RESULTS: A single patient with systemic juvenile rheumatoid arthritis experienced MAS in the post-transplant period. This condition was differentiated from other systematic post-transplant inflammatory conditions, including disseminated intravascular coagulation, engraftment syndrome and capillary leak. Extreme hyperferritinemia (> 150,000 ng/mL) was a distinguishing feature. The patient responded to combination glucocorticosteroids, IVIG and cyclosporine A. CONCLUSIONS: MAS occurs rarely after HCT, and is characterized by severe systemic inflammation and elevated serum ferritin. Early recognition and treatment may lead to a favorable outcome. Funding: Indiana Univsersity School of Medicine
791
Assessment of Histamine Release and Immunomodulation Induced by Restorative Dental Materials A. A. Babakhin1, A. I. Volozhin2, L. N. Kazarina2, O. O. Guschina2, J. A. Babakhina2, L. M. DuBuske3; 1National Research Center - Institute of Immunology, Ministry of Health of Russia, Moscow, RUSSIAN FEDERATION, 2Moscow Medical and Dental University, Moscow, RUSSIAN FEDERATION, 3Immunology Research Institute of New England, Gardner, MA. RATIONALE: Dental materials (DM) may modulate immune response. METHODS: DM Prizmafil (P), FiltekTM Z250 (F) and XRV Herculite Prodigy (H) were placed subcutaneously in (CBAxC57Bl/6)F1 mice (500 mg/mouse) one week before, simultaneously with or one week after immunization using 10 g/mouse of ovalbumin (OA). Anti-OA IgE and IgG antibodies were detected by passive cutaneous anaphylaxis and ELISA respectively. DM were pulverized and incubated in PIPES buffer at 37 C for 48 h, separated by centrifugation and supernatants (SNs) were assessed for leukocyte histamine release. RESULTS: Mice treated with P and H before or simultaneously with primary immunization had lower levels of anti-OA IgE than control. Mice treated with F had increased levels of anti-OA IgE. After the second and third immunizations, mice treated with P and H before immunization had lower levels of anti-OA IgG compared with control mice. When P, F and H were given either simultaneously or one week after primary immunization, levels of anti-OA IgG were greater than control. SN from F demonstrated significant HR while SN from P and H induced HR comparable to control. CONCLUSIONS: Dental materials may alter IgE and IgG responses to allergen and release histamine from blood basophils. Funding: IRINE and National Research Center – Institute of Immunology
792
MONDAY
Inhibition of Indoleamine 2,3-Dioxygenase does not Impede Oral Tolerance C. C. Bowman, M. J. DeVito, D. G. Ross, M. J. K. Selgrade; NHEERL, USEPA, Research Triangle Park, NC. RATIONALE: Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolizing enzyme, regulates immune tolerance through inhibition of T-cell proliferation. Pharmacologic inhibition of IDO, which causes fetal rejection and increased tumor resistance in mice, may prove useful in cancer treatment. IDO’s role in tolerance and high levels of expression in the intestine led us to hypothesize that it may function to maintain oral tolerance. METHODS: Initial pharmacokinetic studies were done to achieve relevant levels of the IDO inhibitor 1-methyl-tryptophan (1-MT) during antigen presentation. C3H/HeJ mice were orally treated with 750 mg/kg of 1-MT, a dose previously shown to enhance tumor rejection, and concurrently exposed to a tolerizing dose of ovalbumin (OVA). Experimental groups consisted of: vehicle, 1-MT, vehicle/OVA, or 1-MT/OVA. Following systemic immunization of all groups with OVA and alum, OVA-specific serum IgG and IgE were measured. RESULTS: Concomitant exposure to OVA and 1-MT did not enhance the subsequent immune response to OVA. Levels of OVA-specific antibody in animals with prior oral exposure to the antigen were reduced by at least half relative to those observed in animals with no prior exposure, regardless of inhibition of IDO. CONCLUSIONS: Transient inhibition of IDO at the time of oral antigen exposure does not prevent induction of oral tolerance. 1-MT does not function as an oral adjuvant under these experimental conditions, and appears unlikely to increase the risk of food allergy. (This abstract does not reflect EPA policy.)
789