- Email: [email protected]
Pretransplant lymphoproliferative disease in an infant with severe combined immunodeficiency (SCID)
J ALLERGY CLIN IMMUNOL VOLUME 111, NUMBER 2
1=
Pretransplunt Lymphoproliferative Disease in an Infant with Severe Combined Immunodeficiency(SCID)
L. J. K o b r y n s k i ], C. Abramowsky2; IPediatrics, Emory University, Atlanta, GA, 2Pathology, Emory University, Atlanta, GA. INTRODUCTION: Benign monoclonal/polyclonal gammopathies and lymphoproliferative diseases have been described post-bone marrow transplantation (BMT) for primary immunodeficiencies (PI) and malignancies. We report a 4 month male with RAGI deficient SCID, with a monoclonal lgA gammopathy. CASE: At diagnosis, the absolute lymphocyte count was 500 cells/mm 3, serum IgG and IgM were absent, IgA was 1200. He had a diffuse erythematous rash, draining ears, cervical, axillary and inguinal lymphadenopathy. CD3, CD4, CD8, CDI9 cells were very low, mitogen responses were absent. The serum IgA rose 200mg/dl per week. Lymph node biopsy showed the absence of germinal centers and large clusters of plasma cells. All these cells were IgA+ with a lambda chain restriction. EBV, LMP-I and EBER in situ studies were negative. EBV PCR and CMV cultures were negative. Lambda light chains were present in the urine. CD20, CD45+ lymphocytes characteristic of mature B cells, were found by flow cytometry of lymph nodes and BMA, consistent with post-transplant lymphoproliferative disease (PTLD). Maternal cells were demonstrated in peripheral blood, lymph nodes and skin, by HLA typing and FISH probes for X and Y. CONCLUSIONS: We theorize that transplacental passage of maternal B cells, combined with the absence of normal T cell regulatory mechanisms led to the clonal expansion of IgA producing B cells. While lymphoproliferative disease and multiclonal gammopathies have been described in children following BMT, this is the first description of a lambda chain restricted IgA monoclonal gammopathy due to maternal cells in a SCID patient prior to BMT.
Abstracts
1
I
$223
The Affects of on Aged Immune System on HIV: The Course of HIV in Elderly Patients Compared with a YoungerGroup When Aggressive Highly Active Antiretroviral Therapy is Instituted
N. S h a r m a ], M. Lee-Wong2; ]Department of Internal Medicine, Beth Israel Medical Center, New York, Nu 2Divison of Clinical Immunology and Allergy, Beth Israel Medical Center, New York, NY. RATIONALE: Impaired humoral and T lymphocyte functioning and delayed recognition and treatment of HIV may put elderly patients at risk for rapid progression of this disease. We conducted a retrospective study of CD4 counts and viral loads in two age groups to investigate whether elderly HIV subjects, if given the same aggressive treatment, can fare as well as younger counterparts. METHODS: A randomized sample of patients with HIV infection was generated from an inner city HIV clinic, where all patients regardless of age are given aggressive management by HIV specialists. 31 patients were obtained for each of two age groups (>63 years and 20-30 years). Retrospective chart review was done. CD4 and viral loads on the first visit and at four-month intervals up to one year after were obtained. Demographics such as H1V risk factors, medical co-morbidities and incidence of opportunistic infections were also collected. RESULTS: Comparison of CD4 counts and viral loads over twelve months showed no statistically significant difference in the course of HIV or AIDS between the two patient populations. Comparison of HIV risk factors also showed no statistically significant difference between the two groups. CONCLUSIONS: When treated in a standardized fashion, CD4 count and viral load response to therapy was statistically similar in the two age groups. Aggressive treatment in elderly patients can play a crucial role in slowing the natural tendency of a more rapid course of HIV in this population burdened with an already declining immune system.
Funding: Self-funded
618 ImmunepatientsResponseto Hepatitis A Vaccination in HIV Positive 616 with Increased Apoptosis in Monooytes of XLA Patients S,imulated Pneumococcal Antigen Funding: Self-funded
F. R. Vallejos ], E. J. Saturno 2, C. M. Moore 2, R. U. Sorensen 2, A. Ochoa2,3; JPediatrics, LSU Health Sciences Center, New Orleans, LA, 2pediatrics, LSU Health Science Center, New Orleans, LA, 3Tumor Immunology Program, Stanley S. Scott Cancer, LSU Health Science Center, New Orleans, LA. Patients with X-linked agammaglobulinemia (XLA) experience recurrent respiratory infections that lead to lung complications such as bronchiectasis and pulmonary fibrosis. XLA is caused by a mutation in Bruton's tyrosine kinase (Btk) and affects males in the first year o f life who exhibit a severe deficit in mature B cells and a profound decrease in circulating immunoglobulins. Btk is also expressed in monocytes but not T lymphocytes and NK cells. Some investigators have shown that the absence of Btk in monocytes produces a mild impairment in degranulation and profound defects in the production of some cytokines. We hypothesized that the absence of Btk in monocytes promotes the induction of apoptosisnecrosis when activated by bacterial antigens. Using an apoptosis-necrosis kit that detects the expression ofAnexin V versus Propidium Iodide we found that macrophages from XLA patients had a two told higher rate of apoptosis when stimulated with pneumococcal antigens as compared to normal controls. Btk deficiency did not change the normal expression of adhesion molecules and complement receptors in monocytes. Is possible that the increased apoptosis in monocytes may play a role in the pathogenesis and lung disease in those patients.
H. Y a r m o h a m m a d P , C. Feucht 2, S. Weissman3; 1Allergy and Immunology, Mt. Sinai Hospital, New York, NY, -"Louis Stokes Cleveland VAMC, Cleveland, OH, 3St. Raphael Hospital, New Haven, CT. INTRODUCTION: Hepatitis A is common in HIV+ patients. Superinfection with HAV in patients with chronic hepatitis C can lead to fulminant hepatic failure. The USPHS/IDSA guidelines recommend that all susceptible HIV patients at increased risk for HAV, or with chronic liver disease, be vaccinated against HAV. Response to HAV vaccine has not been well studied in HIV patients. Objectives: To assess the affect of CD4 count, VL, ART, hepatitis B and C co-infections on response to HAV vaccine in HIV positive patients. METHODS: HIV patients were tested for HAV IgG. Patients with negative HAV IgG received two HAV vaccines 6 to 12 months apart. Post HAV lgG response was measured after the 2nd vaccine. Data analysis was done by SAS software. RESULTS: 230 patients were evaluated. 72 patients were excluded because of (+) HAV lgG. From 158 included, 45 patients had completed their HAV vaccination series. 25 of 45 patients had positive post vaccine HAV IgG. There was no difference in age, race, gender, ART use, or VL between HAV vaccine responders and nonresponders. 21% of responders had CD4200 and VL <500 copies/ml at the time of vaccine (OR 2.1, CI 0.47-9.965, p=0.3; and OR 2.2, CI 0.54-8.70, p=0.2, respectively). CONCLUSIONS: 55% of our HIV (+) patients responded to HAV vaccine. This is much lower than reported rates of 100% in HIV(-) patients. A trend for greater response rates was seen in patients with higher CD4 counts at time of vaccine.
Funding: Self-fitnded
1=
Pretransplunt Lymphoproliferative Disease in an Infant with Severe Combined Immunodeficiency(SCID)
L. J. K o b r y n s k i ], C. Abramowsky2; IPediatrics, Emory University, Atlanta, GA, 2Pathology, Emory University, Atlanta, GA. INTRODUCTION: Benign monoclonal/polyclonal gammopathies and lymphoproliferative diseases have been described post-bone marrow transplantation (BMT) for primary immunodeficiencies (PI) and malignancies. We report a 4 month male with RAGI deficient SCID, with a monoclonal lgA gammopathy. CASE: At diagnosis, the absolute lymphocyte count was 500 cells/mm 3, serum IgG and IgM were absent, IgA was 1200. He had a diffuse erythematous rash, draining ears, cervical, axillary and inguinal lymphadenopathy. CD3, CD4, CD8, CDI9 cells were very low, mitogen responses were absent. The serum IgA rose 200mg/dl per week. Lymph node biopsy showed the absence of germinal centers and large clusters of plasma cells. All these cells were IgA+ with a lambda chain restriction. EBV, LMP-I and EBER in situ studies were negative. EBV PCR and CMV cultures were negative. Lambda light chains were present in the urine. CD20, CD45+ lymphocytes characteristic of mature B cells, were found by flow cytometry of lymph nodes and BMA, consistent with post-transplant lymphoproliferative disease (PTLD). Maternal cells were demonstrated in peripheral blood, lymph nodes and skin, by HLA typing and FISH probes for X and Y. CONCLUSIONS: We theorize that transplacental passage of maternal B cells, combined with the absence of normal T cell regulatory mechanisms led to the clonal expansion of IgA producing B cells. While lymphoproliferative disease and multiclonal gammopathies have been described in children following BMT, this is the first description of a lambda chain restricted IgA monoclonal gammopathy due to maternal cells in a SCID patient prior to BMT.
Abstracts
1
I
$223
The Affects of on Aged Immune System on HIV: The Course of HIV in Elderly Patients Compared with a YoungerGroup When Aggressive Highly Active Antiretroviral Therapy is Instituted
N. S h a r m a ], M. Lee-Wong2; ]Department of Internal Medicine, Beth Israel Medical Center, New York, Nu 2Divison of Clinical Immunology and Allergy, Beth Israel Medical Center, New York, NY. RATIONALE: Impaired humoral and T lymphocyte functioning and delayed recognition and treatment of HIV may put elderly patients at risk for rapid progression of this disease. We conducted a retrospective study of CD4 counts and viral loads in two age groups to investigate whether elderly HIV subjects, if given the same aggressive treatment, can fare as well as younger counterparts. METHODS: A randomized sample of patients with HIV infection was generated from an inner city HIV clinic, where all patients regardless of age are given aggressive management by HIV specialists. 31 patients were obtained for each of two age groups (>63 years and 20-30 years). Retrospective chart review was done. CD4 and viral loads on the first visit and at four-month intervals up to one year after were obtained. Demographics such as H1V risk factors, medical co-morbidities and incidence of opportunistic infections were also collected. RESULTS: Comparison of CD4 counts and viral loads over twelve months showed no statistically significant difference in the course of HIV or AIDS between the two patient populations. Comparison of HIV risk factors also showed no statistically significant difference between the two groups. CONCLUSIONS: When treated in a standardized fashion, CD4 count and viral load response to therapy was statistically similar in the two age groups. Aggressive treatment in elderly patients can play a crucial role in slowing the natural tendency of a more rapid course of HIV in this population burdened with an already declining immune system.
Funding: Self-funded
618 ImmunepatientsResponseto Hepatitis A Vaccination in HIV Positive 616 with Increased Apoptosis in Monooytes of XLA Patients S,imulated Pneumococcal Antigen Funding: Self-funded
F. R. Vallejos ], E. J. Saturno 2, C. M. Moore 2, R. U. Sorensen 2, A. Ochoa2,3; JPediatrics, LSU Health Sciences Center, New Orleans, LA, 2pediatrics, LSU Health Science Center, New Orleans, LA, 3Tumor Immunology Program, Stanley S. Scott Cancer, LSU Health Science Center, New Orleans, LA. Patients with X-linked agammaglobulinemia (XLA) experience recurrent respiratory infections that lead to lung complications such as bronchiectasis and pulmonary fibrosis. XLA is caused by a mutation in Bruton's tyrosine kinase (Btk) and affects males in the first year o f life who exhibit a severe deficit in mature B cells and a profound decrease in circulating immunoglobulins. Btk is also expressed in monocytes but not T lymphocytes and NK cells. Some investigators have shown that the absence of Btk in monocytes produces a mild impairment in degranulation and profound defects in the production of some cytokines. We hypothesized that the absence of Btk in monocytes promotes the induction of apoptosisnecrosis when activated by bacterial antigens. Using an apoptosis-necrosis kit that detects the expression ofAnexin V versus Propidium Iodide we found that macrophages from XLA patients had a two told higher rate of apoptosis when stimulated with pneumococcal antigens as compared to normal controls. Btk deficiency did not change the normal expression of adhesion molecules and complement receptors in monocytes. Is possible that the increased apoptosis in monocytes may play a role in the pathogenesis and lung disease in those patients.
H. Y a r m o h a m m a d P , C. Feucht 2, S. Weissman3; 1Allergy and Immunology, Mt. Sinai Hospital, New York, NY, -"Louis Stokes Cleveland VAMC, Cleveland, OH, 3St. Raphael Hospital, New Haven, CT. INTRODUCTION: Hepatitis A is common in HIV+ patients. Superinfection with HAV in patients with chronic hepatitis C can lead to fulminant hepatic failure. The USPHS/IDSA guidelines recommend that all susceptible HIV patients at increased risk for HAV, or with chronic liver disease, be vaccinated against HAV. Response to HAV vaccine has not been well studied in HIV patients. Objectives: To assess the affect of CD4 count, VL, ART, hepatitis B and C co-infections on response to HAV vaccine in HIV positive patients. METHODS: HIV patients were tested for HAV IgG. Patients with negative HAV IgG received two HAV vaccines 6 to 12 months apart. Post HAV lgG response was measured after the 2nd vaccine. Data analysis was done by SAS software. RESULTS: 230 patients were evaluated. 72 patients were excluded because of (+) HAV lgG. From 158 included, 45 patients had completed their HAV vaccination series. 25 of 45 patients had positive post vaccine HAV IgG. There was no difference in age, race, gender, ART use, or VL between HAV vaccine responders and nonresponders. 21% of responders had CD4200 and VL <500 copies/ml at the time of vaccine (OR 2.1, CI 0.47-9.965, p=0.3; and OR 2.2, CI 0.54-8.70, p=0.2, respectively). CONCLUSIONS: 55% of our HIV (+) patients responded to HAV vaccine. This is much lower than reported rates of 100% in HIV(-) patients. A trend for greater response rates was seen in patients with higher CD4 counts at time of vaccine.
Funding: Self-fitnded