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Clinical and Virological Characteristics Of HIV-Associated Lymphomas In Patients With Perinatally-Acquired HIV In The Era Of Antiretroviral Therapy
Abstracts AB97
J ALLERGY CLIN IMMUNOL VOLUME 133, NUMBER 2
An Adult With Disseminated Herpes Zoster Infection Found To Have Rare Combined CD4, CD8 T-Cell and NK-Cell Deficiency Neil Parikh, MD1, Joseph S. Yusin, MD, FAAAAI2; 1UCLA-VA Greater Los Angeles Healthcare System, Los Angeles, CA, 2VA Greater Los Angeles Health Care System, Los Angeles, CA. RATIONALE: Cellular immuodeficiencies other than those associated with human immunodeficiency virus (HIV) are rare, and they usually arise in early childhood (eg, severe combined immune deficiency). Only idiopathic CD4+ lymphopenia has been well-defined to develop in adulthood. Case reports have reported adult-onset T-cell deficiency associated with impaired CD2 expression, and a subtype of common variable immunodeficiency with severe T-cell defect. Here we present an adult with recurrent herpes zoster infection found to have CD4, CD8 T-cell and NK cell deficiency. METHODS: HIV DNA/RNA PCR and lymphocyte mitogen stimulation were performed by Quest Diagnostics. RESULTS: This Caucasian male initially presented at age 7 with acute varicella infection. At age 25 the patient presented with pruritic rash involving T10 dermatome, diagnosed with herpes zoster. At age 40, patient presented with diffuse papulovesicular rash, malaise, and headache. Vesicular fluid showed positive varicella zoster virus (VZV) PCR. Immune evaluation was performed at this point. CD3+/CD4+ T cell 248 x106 cells/L, CD3/CD8 T cell 94 x106 cells/L, and CD3-/CD56+ NK cell 69 x106 cells/L, varicella IgG 1.51 g/dL. White blood cell count, quantitative immunoglobulins IgG, IgM, IgA, IgE, B cell count, streptococcal antibody titer, lymphocyte mitogen stimulation, HIV RNA PCR, and tetanus toxoid/tuberculin/candida delayed hypersensitivity skin tests were normal. Patient was given hepatitis B and herpes zoster vaccinations. CONCLUSIONS: We believe this is a unique, rare case of adult-onset combined CD4, CD8 T-cell and NK cell deficiency. This novel late-onset cellular immunodeficiency is of unknown prevalence, genetic origin, and may be of very significant clinical utility in the future.
336
Clinical and Virological Characteristics Of HIV-Associated Lymphomas In Patients With Perinatally-Acquired HIV In The Era Of Antiretroviral Therapy Dr. Jasmeen S. Dara, MD1, Dr. Stefan Barta2, Dr. Jenny Shliozberg, MD, FAAAAI3; 1Montefiore Medical Center/Albert Einstein College of Medicine, 2Montefiore Medical Center, 3Montefiore Medical Center, Bronx, NY. RATIONALE: Since the advent of cART, HIV-associated lymphomas have decreased in incidence and there has been a shift towards Burkitt (BL) and Hodgkin lymphoma (HL). However, in contrast to non-Hodgkin lymphoma, HL has been increasing in incidence. EBV, most common oncogenic virus involved in pathogenesis, is present in approximately 40% of cases. To date, there have been no reports of HIV-associated lymphoma in patients with perinatally-acquired HIV in the US. METHODS: Clinical, virological, and histologic characteristics of HIVassociated lymphomas in 5 patients with perinatally-acquired HIV were collected restrospectively through chart review. RESULTS: Median age at diagnosis was 24 years [22, 25]. All patients had moderate to severe immunosuppression (median CD4 220/mL [85.5, 263.0], median viral load 1761 copies/mL [113, 2X106]) at the time of diagnosis. The median CD4 nadir was 350/mL [4, 446.5] and duration at nadir was 48 months [18, 72]. Two patients had diffuse large B-cell lymphoma (DLBCL), one of which had a plasmablastic subtype of DLBCL. Two patients had nodular sclerosing HL, and one had BL. Four patients had serologic and/or immunohistochemical evidence of EBV infection. Four patients had favorable response to chemotherapy, no disease progression, and median disease free survival of 3.4 years [1.2, 7.1] thus far. One patient, with DLBCL, had disease progression including leptomeningeal involvement and is currently receiving salvage chemotherapy. CONCLUSIONS: In this series, HIV-associated lymphomas are found in patients with perinatally-acquired HIV during the second decade of life. Prognosis remains favorable for those that respond to first line chemotherapy.
337
Study On Air Pollution and Respiratory Health Of Children In Delhi, India Ms. Jincy Mathew, M.Tech1, Dr. Radha Goyal, PhD2, Dr. Krinshna K. Taneja, PhD3, Dr. Naveen Arora, PhD4; 1CSIR- Institute of Genomics and Integrative Biology, Delhi, India, 2CSIR- National Environmental Engineering Research Institute, Delhi, India, 3CSIR- Istitute of Genomics and Integrative Biology, Delhi, India, 4CSIR Institute of Genomics and Integrative Biology, New Delhi, India. RATIONALE: Air pollutants may cause respiratory problems in children during adolescence. The study was aimed at assessing the respiratory health of children exposed to pollution in different areas of Delhi. METHODS: Schools were selected from commercial-Chandni Chowk (CC), industrial- Mayapuri (MP) and residential -Sarojini Nagar (SN) areas. Indoor and outdoor levels of SO2, NOx and Particulate matter (PM) were estimated using samplers in classrooms and at monitoring stations. Questionnaire was designed based on internationally valid questionnaires for respiratory illness. Students completed the questionnaire and performed spirometry test. RESULTS: Indoor and outdoor PM10 concentration was highest in CC (8156354.45 & 337685 mg/m3) and lower in MP (694.66322.9 & 274678mg/m3) and SN (534.3694.22 & 197648 mg/m3). These were too high & above the permissible limits of 100mg/m3. However, levels of SO2 and NOxwere below the limit. Students (1814) aged between 12–16 years participated in the survey. Questionnaire data showed that ‘‘wheeze, cough and cold’’ were most prevalent in CC (29.6%) panel of students followed by MP (15.9%). Spirometry tests demonstrated that 19% of CC & 14% of MP subjects suffered mild obstruction whereas 16% of CC & 32% of MP subjects had severe obstruction. Conditional logistic regression analysis of the association between chronic exposure to PM and respiratory symptoms showed a significant positive relationship in these areas. CONCLUSIONS: Commercial and industrial zones with high traffic movement and human activities contribute more PM which affects the pulmonary health. The study indicates that high pollution levels may lead to respiratory illness in children.
338
Trans-Generational Transmission Of Ozone – Induced Airway Dysfunction Prof. Park Choon Sik, Mr. Da-Jeong Bae, Dr. Jong-Sook Park, Dr. Jang An Soo; Soonchunhyang University Bucheon Hospital, Gyeonggi-Do, South Korea. RATIONALE: Epigenetics is responsible – environmental interaction of asthma development. The role of epigenetics behind ozone - induced airway dysfunction is not known yet. METHODS: 6 weeks old BALB/C female mice were exposed to filter air or O3 (2ppm, 3hr/day, day1 to day 21). Airway resistance (Pehn), and BAL procedure were performed at weekly interval. For trans-generational transmission study, 6weeks old BALB/C female mice (F0) were exposed to filter air (Air-F0) or O3 (1ppm, Ozone-F0) during pregnancy. Pehn was measured at 5 and 6 weeks of age in F1;F3 mice grown up in filter air, and cytokines (IL-1a, ß, 4, 5, 8, 9, 10, 12, 17, 22, 23, LxA4, RvE1, PGE2) were measured in BALF using ELISA kit. mRNA expression of DNMTs, MeCP2, MBDs, HDAC3, Chrm1,2,3 and ADRß2 genes were measured in RNA extracted from lung tissue using Real-Time PCR. RESULTS: After Ozone exposure, Pehn value was significantly increased in a time dependent manner with concomitant BAL neutrophilia. MBDs and HDAC3 increased at hour 3, while DNMTs, MeCP2 started to increase at day 14 exposure. In the trans-generational models, F1; F3 mice born from Ozone-F0 showed persistent elevation of Pehn and BAL neutrophilia. IL-5, 8, 9,10, and 12 elevated in F1 of Ozone F0, but returned in F2 and F3 compared to those of Air F0. DNMTs of Ozone-F0 to Ozone-F3 increased, while Chrm2 and ADRß2 were decreased compared to those of AirF0. CONCLUSIONS: Ozone - induced airway dysfunction may be transmitted to F3 generation with altered expression of the genes related with airway function potentially via epigenetic changes.
SUNDAY
335
J ALLERGY CLIN IMMUNOL VOLUME 133, NUMBER 2
An Adult With Disseminated Herpes Zoster Infection Found To Have Rare Combined CD4, CD8 T-Cell and NK-Cell Deficiency Neil Parikh, MD1, Joseph S. Yusin, MD, FAAAAI2; 1UCLA-VA Greater Los Angeles Healthcare System, Los Angeles, CA, 2VA Greater Los Angeles Health Care System, Los Angeles, CA. RATIONALE: Cellular immuodeficiencies other than those associated with human immunodeficiency virus (HIV) are rare, and they usually arise in early childhood (eg, severe combined immune deficiency). Only idiopathic CD4+ lymphopenia has been well-defined to develop in adulthood. Case reports have reported adult-onset T-cell deficiency associated with impaired CD2 expression, and a subtype of common variable immunodeficiency with severe T-cell defect. Here we present an adult with recurrent herpes zoster infection found to have CD4, CD8 T-cell and NK cell deficiency. METHODS: HIV DNA/RNA PCR and lymphocyte mitogen stimulation were performed by Quest Diagnostics. RESULTS: This Caucasian male initially presented at age 7 with acute varicella infection. At age 25 the patient presented with pruritic rash involving T10 dermatome, diagnosed with herpes zoster. At age 40, patient presented with diffuse papulovesicular rash, malaise, and headache. Vesicular fluid showed positive varicella zoster virus (VZV) PCR. Immune evaluation was performed at this point. CD3+/CD4+ T cell 248 x106 cells/L, CD3/CD8 T cell 94 x106 cells/L, and CD3-/CD56+ NK cell 69 x106 cells/L, varicella IgG 1.51 g/dL. White blood cell count, quantitative immunoglobulins IgG, IgM, IgA, IgE, B cell count, streptococcal antibody titer, lymphocyte mitogen stimulation, HIV RNA PCR, and tetanus toxoid/tuberculin/candida delayed hypersensitivity skin tests were normal. Patient was given hepatitis B and herpes zoster vaccinations. CONCLUSIONS: We believe this is a unique, rare case of adult-onset combined CD4, CD8 T-cell and NK cell deficiency. This novel late-onset cellular immunodeficiency is of unknown prevalence, genetic origin, and may be of very significant clinical utility in the future.
336
Clinical and Virological Characteristics Of HIV-Associated Lymphomas In Patients With Perinatally-Acquired HIV In The Era Of Antiretroviral Therapy Dr. Jasmeen S. Dara, MD1, Dr. Stefan Barta2, Dr. Jenny Shliozberg, MD, FAAAAI3; 1Montefiore Medical Center/Albert Einstein College of Medicine, 2Montefiore Medical Center, 3Montefiore Medical Center, Bronx, NY. RATIONALE: Since the advent of cART, HIV-associated lymphomas have decreased in incidence and there has been a shift towards Burkitt (BL) and Hodgkin lymphoma (HL). However, in contrast to non-Hodgkin lymphoma, HL has been increasing in incidence. EBV, most common oncogenic virus involved in pathogenesis, is present in approximately 40% of cases. To date, there have been no reports of HIV-associated lymphoma in patients with perinatally-acquired HIV in the US. METHODS: Clinical, virological, and histologic characteristics of HIVassociated lymphomas in 5 patients with perinatally-acquired HIV were collected restrospectively through chart review. RESULTS: Median age at diagnosis was 24 years [22, 25]. All patients had moderate to severe immunosuppression (median CD4 220/mL [85.5, 263.0], median viral load 1761 copies/mL [113, 2X106]) at the time of diagnosis. The median CD4 nadir was 350/mL [4, 446.5] and duration at nadir was 48 months [18, 72]. Two patients had diffuse large B-cell lymphoma (DLBCL), one of which had a plasmablastic subtype of DLBCL. Two patients had nodular sclerosing HL, and one had BL. Four patients had serologic and/or immunohistochemical evidence of EBV infection. Four patients had favorable response to chemotherapy, no disease progression, and median disease free survival of 3.4 years [1.2, 7.1] thus far. One patient, with DLBCL, had disease progression including leptomeningeal involvement and is currently receiving salvage chemotherapy. CONCLUSIONS: In this series, HIV-associated lymphomas are found in patients with perinatally-acquired HIV during the second decade of life. Prognosis remains favorable for those that respond to first line chemotherapy.
337
Study On Air Pollution and Respiratory Health Of Children In Delhi, India Ms. Jincy Mathew, M.Tech1, Dr. Radha Goyal, PhD2, Dr. Krinshna K. Taneja, PhD3, Dr. Naveen Arora, PhD4; 1CSIR- Institute of Genomics and Integrative Biology, Delhi, India, 2CSIR- National Environmental Engineering Research Institute, Delhi, India, 3CSIR- Istitute of Genomics and Integrative Biology, Delhi, India, 4CSIR Institute of Genomics and Integrative Biology, New Delhi, India. RATIONALE: Air pollutants may cause respiratory problems in children during adolescence. The study was aimed at assessing the respiratory health of children exposed to pollution in different areas of Delhi. METHODS: Schools were selected from commercial-Chandni Chowk (CC), industrial- Mayapuri (MP) and residential -Sarojini Nagar (SN) areas. Indoor and outdoor levels of SO2, NOx and Particulate matter (PM) were estimated using samplers in classrooms and at monitoring stations. Questionnaire was designed based on internationally valid questionnaires for respiratory illness. Students completed the questionnaire and performed spirometry test. RESULTS: Indoor and outdoor PM10 concentration was highest in CC (8156354.45 & 337685 mg/m3) and lower in MP (694.66322.9 & 274678mg/m3) and SN (534.3694.22 & 197648 mg/m3). These were too high & above the permissible limits of 100mg/m3. However, levels of SO2 and NOxwere below the limit. Students (1814) aged between 12–16 years participated in the survey. Questionnaire data showed that ‘‘wheeze, cough and cold’’ were most prevalent in CC (29.6%) panel of students followed by MP (15.9%). Spirometry tests demonstrated that 19% of CC & 14% of MP subjects suffered mild obstruction whereas 16% of CC & 32% of MP subjects had severe obstruction. Conditional logistic regression analysis of the association between chronic exposure to PM and respiratory symptoms showed a significant positive relationship in these areas. CONCLUSIONS: Commercial and industrial zones with high traffic movement and human activities contribute more PM which affects the pulmonary health. The study indicates that high pollution levels may lead to respiratory illness in children.
338
Trans-Generational Transmission Of Ozone – Induced Airway Dysfunction Prof. Park Choon Sik, Mr. Da-Jeong Bae, Dr. Jong-Sook Park, Dr. Jang An Soo; Soonchunhyang University Bucheon Hospital, Gyeonggi-Do, South Korea. RATIONALE: Epigenetics is responsible – environmental interaction of asthma development. The role of epigenetics behind ozone - induced airway dysfunction is not known yet. METHODS: 6 weeks old BALB/C female mice were exposed to filter air or O3 (2ppm, 3hr/day, day1 to day 21). Airway resistance (Pehn), and BAL procedure were performed at weekly interval. For trans-generational transmission study, 6weeks old BALB/C female mice (F0) were exposed to filter air (Air-F0) or O3 (1ppm, Ozone-F0) during pregnancy. Pehn was measured at 5 and 6 weeks of age in F1;F3 mice grown up in filter air, and cytokines (IL-1a, ß, 4, 5, 8, 9, 10, 12, 17, 22, 23, LxA4, RvE1, PGE2) were measured in BALF using ELISA kit. mRNA expression of DNMTs, MeCP2, MBDs, HDAC3, Chrm1,2,3 and ADRß2 genes were measured in RNA extracted from lung tissue using Real-Time PCR. RESULTS: After Ozone exposure, Pehn value was significantly increased in a time dependent manner with concomitant BAL neutrophilia. MBDs and HDAC3 increased at hour 3, while DNMTs, MeCP2 started to increase at day 14 exposure. In the trans-generational models, F1; F3 mice born from Ozone-F0 showed persistent elevation of Pehn and BAL neutrophilia. IL-5, 8, 9,10, and 12 elevated in F1 of Ozone F0, but returned in F2 and F3 compared to those of Air F0. DNMTs of Ozone-F0 to Ozone-F3 increased, while Chrm2 and ADRß2 were decreased compared to those of AirF0. CONCLUSIONS: Ozone - induced airway dysfunction may be transmitted to F3 generation with altered expression of the genes related with airway function potentially via epigenetic changes.
SUNDAY
335