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Experience with a 20% Subcutaneous Immunoglobulin (Hizentra®) in Children with Primary Immunodeficiency Diseases - A Single-Center Review
AB154 Abstracts
544
MONDAY
Disseminated Aspergillosis in Adult-Onset Severe Combined Immunodeficiency: A Case of Xcind Syndrome Kellie J. Lim, MD1, E. Richard Stiehm, MD, FAAAAI2, Richard Gatti, MD3, Otto Yang, MD4; 1UCLA, Department of Pediatrics, Division of Allergy and Immunology, Los Angeles, CA, 2Division of Allergy and Immunology, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 3UCLA, Department of Pathology & Laboratory Medicine, 4UCLA, Department of Medicine, Division of Infectious Disease. RATIONALE: The onset and diagnosis of severe combined immunodeficiency (SCID) typically occurs in infancy; however, in rare cases it is diagnosed in adulthood. A 24 year old male of normal intelligence presented with a seizure and was later diagnosed with disseminated aspergillosis with intracranial and pulmonary involvement. He had profound CD4 lymphopenia and subsequently developed hypogammaglobulinemia. He did not have history of recurrent infections and was previously in good health. Physical findings included dysmorphic facies, short stature, and microcephaly; thus radiosensitivity syndromes were considered. METHODS: Colony survival assay (CSA), Western blots, and DNA sequencing were performed. RESULTS: CSA confirmed radiosensitivity. Western blots were performed for genes associated with double-stranded DNA breakage repair, and they were normal for: ATM (ataxia telangiectasia), NBS (Nijmegen breakage syndrome), FANCD2 (Fanconi anemia), APTX (ataxia-oculomotor apraxia syndrome), Artemis (Omenn syndrome and Athabascan-type severe combined immunodeficiency), PNPK, MRE11, and RAD50. Antibody for DNA ligase IV on fibroblast lysates prepared in RIPA buffer failed to detect DNA ligase IV. DNA sequencing of DNA ligase IV did not reveal mutations. CONCLUSIONS: DNA ligase IV deficiency is an XCIND syndrome: X-ray-irradiation sensitivity, Cancer susceptibility, Immunodeficiency, Neurological abnormalities, and Double-strand DNA breakage. DNA ligase IV plays a major role in non-homologous end joining (NHEJ) and is also involved in physiological V(D)J rearrangement and class switching, thereby leading to immunodeficiency when a mutation occurs.
545
Abnormalities in CD4 and CD8 Lymphocyte Subpopulations in Patients with Common Variable Immunodeficiency Amanda J. Seba, Norma de Paula Motta Rubini, Albertina VarandasCapelo, Eliane Miranda da Silva, Fernando Samuel Sion, Clety Larissa, Angulo Llerena, Carlos Alberto Morais-de-Sa; Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. RATIONALE: Patients with CVID constitute a heterogeneous group with a spectrum of several immunological abnormalities and different clinical phenotypes. Our objective was to describe the frequency of abnormalities in CD4 and CD8 lymphocyte subpopulations in CVID patients and investigate the impact of these abnormalities on clinical profile and prognosis. METHODS: A retrospective, longitudinal study was conducted of patients with CVID (PAGID diagnostic criteria) in follow-up for a period of >1 year. Patients were assessed for baseline CD4 and CD8 lymphocyte count before starting treatment with intravenous human immunoglobulin. RESULTS: We analyzed 13 patients - 9 females (69%) - aged between 19 and 62 years (median536) in clinical follow-up for a period ranging from 1 to 24 years (median56). Inversion of CD4/CD8 ratio was observed in 54% 7 of the patients. Among these patients, 7 (100%) had recurrent sinusitis, 5 (72%) had bacterial pneumonia, 3 (43%) had severe giardiasis, 3 (43%) had thrombocytopenia, 2 (28%) had pulmonary tuberculosis, 1 (14%) had severe mononucleosis, evolving with lymphocytic interstitial lung disease, and 1 (14%) had malignancy. Among patients without inversion of the CD4/CD8 ratio, the main clinical manifestations were recurrent sinusitis - 6 (100%), bacterial pneumonia - 4 (67%) and malignancy - 1 (17%).
J ALLERGY CLIN IMMUNOL FEBRUARY 2013
CONCLUSIONS: In this series, we found that a high percentage of patients with CVID showed inversion of CD4/CD8 ratio. This immunological abnormality was associated with a profile of more severe clinical manifestations related to cellular immunodeficiency and/or autoimmunity.
546
Experience with a 20% Subcutaneous Immunoglobulin (HizentraÒ) in Children with Primary Immunodeficiency Diseases - A Single-Center Review Rebecca Gregory1, Clare Malcolmson1, Chetan Patel1, Terry Woolley2, Alison Jones1; 1Great Ormond Street Hospital, London, United Kingdom, 2 CSL Behring, West Sussex, United Kingdom. RATIONALE: HizentraÒ (IgPro20), a 20% subcutaneous immunoglobulin (SCIG), has been approved for the treatment of primary immunodeficiency diseases (PID). Licensing studies demonstrated similar or higher serum IgG levels following switch to the more concentrated 20% SCIG from previous immunoglobulin treatment. Here we present effectiveness and safety data from a cohort of children with PID in the UK who switched to 20% SCIG. METHODS: Children/young adults (aged <19 years) switched from VivaglobinÒ (16% SCIG) to 20% SCIG. Patients received the initial dose in hospital; subsequent doses were administered at home. RESULTS: Thirty-seven patients (median age 9.3 years) were evaluated. Patients received a mean HizentraÒ dose of 233.9 mg/kg (range 105–500); dosing schedules were weekly, 10-day, or every two weeks. The average duration of treatment was 9.3 months (range 4–13). Average monthly doses with prior treatment and 20% SCIG were comparable: 649.6 mg/kg (range: 426.7–1188.6) vs 672.1 mg/kg (range 319.1– 1111.1). Mean (SD) serum IgG levels increased from 10.2 (3.5) g/L before 20% SCIG treatment to 11.2 (3.1) g/L during the treatment period. Two severe infections were reported (respiratory infection and peri-orbital cellulitis). No pneumonia cases were reported during 20% SCIG treatment. The annualized rate of days in hospital was 1.1 days/patient/year and that of days missed, 2.3 days/patient/year (preliminary data). There were three treatment-related adverse events: mild local reactions (two) and diarrhea (one). CONCLUSIONS: In real-life clinical practice, switching to 20% SCIG treatment resulted in improved IgG levels and provided effective protection from infections in this small cohort.
544
MONDAY
Disseminated Aspergillosis in Adult-Onset Severe Combined Immunodeficiency: A Case of Xcind Syndrome Kellie J. Lim, MD1, E. Richard Stiehm, MD, FAAAAI2, Richard Gatti, MD3, Otto Yang, MD4; 1UCLA, Department of Pediatrics, Division of Allergy and Immunology, Los Angeles, CA, 2Division of Allergy and Immunology, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 3UCLA, Department of Pathology & Laboratory Medicine, 4UCLA, Department of Medicine, Division of Infectious Disease. RATIONALE: The onset and diagnosis of severe combined immunodeficiency (SCID) typically occurs in infancy; however, in rare cases it is diagnosed in adulthood. A 24 year old male of normal intelligence presented with a seizure and was later diagnosed with disseminated aspergillosis with intracranial and pulmonary involvement. He had profound CD4 lymphopenia and subsequently developed hypogammaglobulinemia. He did not have history of recurrent infections and was previously in good health. Physical findings included dysmorphic facies, short stature, and microcephaly; thus radiosensitivity syndromes were considered. METHODS: Colony survival assay (CSA), Western blots, and DNA sequencing were performed. RESULTS: CSA confirmed radiosensitivity. Western blots were performed for genes associated with double-stranded DNA breakage repair, and they were normal for: ATM (ataxia telangiectasia), NBS (Nijmegen breakage syndrome), FANCD2 (Fanconi anemia), APTX (ataxia-oculomotor apraxia syndrome), Artemis (Omenn syndrome and Athabascan-type severe combined immunodeficiency), PNPK, MRE11, and RAD50. Antibody for DNA ligase IV on fibroblast lysates prepared in RIPA buffer failed to detect DNA ligase IV. DNA sequencing of DNA ligase IV did not reveal mutations. CONCLUSIONS: DNA ligase IV deficiency is an XCIND syndrome: X-ray-irradiation sensitivity, Cancer susceptibility, Immunodeficiency, Neurological abnormalities, and Double-strand DNA breakage. DNA ligase IV plays a major role in non-homologous end joining (NHEJ) and is also involved in physiological V(D)J rearrangement and class switching, thereby leading to immunodeficiency when a mutation occurs.
545
Abnormalities in CD4 and CD8 Lymphocyte Subpopulations in Patients with Common Variable Immunodeficiency Amanda J. Seba, Norma de Paula Motta Rubini, Albertina VarandasCapelo, Eliane Miranda da Silva, Fernando Samuel Sion, Clety Larissa, Angulo Llerena, Carlos Alberto Morais-de-Sa; Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. RATIONALE: Patients with CVID constitute a heterogeneous group with a spectrum of several immunological abnormalities and different clinical phenotypes. Our objective was to describe the frequency of abnormalities in CD4 and CD8 lymphocyte subpopulations in CVID patients and investigate the impact of these abnormalities on clinical profile and prognosis. METHODS: A retrospective, longitudinal study was conducted of patients with CVID (PAGID diagnostic criteria) in follow-up for a period of >1 year. Patients were assessed for baseline CD4 and CD8 lymphocyte count before starting treatment with intravenous human immunoglobulin. RESULTS: We analyzed 13 patients - 9 females (69%) - aged between 19 and 62 years (median536) in clinical follow-up for a period ranging from 1 to 24 years (median56). Inversion of CD4/CD8 ratio was observed in 54% 7 of the patients. Among these patients, 7 (100%) had recurrent sinusitis, 5 (72%) had bacterial pneumonia, 3 (43%) had severe giardiasis, 3 (43%) had thrombocytopenia, 2 (28%) had pulmonary tuberculosis, 1 (14%) had severe mononucleosis, evolving with lymphocytic interstitial lung disease, and 1 (14%) had malignancy. Among patients without inversion of the CD4/CD8 ratio, the main clinical manifestations were recurrent sinusitis - 6 (100%), bacterial pneumonia - 4 (67%) and malignancy - 1 (17%).
J ALLERGY CLIN IMMUNOL FEBRUARY 2013
CONCLUSIONS: In this series, we found that a high percentage of patients with CVID showed inversion of CD4/CD8 ratio. This immunological abnormality was associated with a profile of more severe clinical manifestations related to cellular immunodeficiency and/or autoimmunity.
546
Experience with a 20% Subcutaneous Immunoglobulin (HizentraÒ) in Children with Primary Immunodeficiency Diseases - A Single-Center Review Rebecca Gregory1, Clare Malcolmson1, Chetan Patel1, Terry Woolley2, Alison Jones1; 1Great Ormond Street Hospital, London, United Kingdom, 2 CSL Behring, West Sussex, United Kingdom. RATIONALE: HizentraÒ (IgPro20), a 20% subcutaneous immunoglobulin (SCIG), has been approved for the treatment of primary immunodeficiency diseases (PID). Licensing studies demonstrated similar or higher serum IgG levels following switch to the more concentrated 20% SCIG from previous immunoglobulin treatment. Here we present effectiveness and safety data from a cohort of children with PID in the UK who switched to 20% SCIG. METHODS: Children/young adults (aged <19 years) switched from VivaglobinÒ (16% SCIG) to 20% SCIG. Patients received the initial dose in hospital; subsequent doses were administered at home. RESULTS: Thirty-seven patients (median age 9.3 years) were evaluated. Patients received a mean HizentraÒ dose of 233.9 mg/kg (range 105–500); dosing schedules were weekly, 10-day, or every two weeks. The average duration of treatment was 9.3 months (range 4–13). Average monthly doses with prior treatment and 20% SCIG were comparable: 649.6 mg/kg (range: 426.7–1188.6) vs 672.1 mg/kg (range 319.1– 1111.1). Mean (SD) serum IgG levels increased from 10.2 (3.5) g/L before 20% SCIG treatment to 11.2 (3.1) g/L during the treatment period. Two severe infections were reported (respiratory infection and peri-orbital cellulitis). No pneumonia cases were reported during 20% SCIG treatment. The annualized rate of days in hospital was 1.1 days/patient/year and that of days missed, 2.3 days/patient/year (preliminary data). There were three treatment-related adverse events: mild local reactions (two) and diarrhea (one). CONCLUSIONS: In real-life clinical practice, switching to 20% SCIG treatment resulted in improved IgG levels and provided effective protection from infections in this small cohort.