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Novel insights from adaptor protein 3 complex deficiency
Reviews and feature articles
Continuing Medical Education examination
Novel insights from adaptor protein 3 complex deficiency Instructions for category 1 Continuing Medical Education credit The American Academy of Allergy, Asthma & Immunology is accredited as a provider of Continuing Medical Education (CME) by the Accreditation Council for Continuing Medical Education. Test ID no.: mai00125 Contact hours: 1.0 Expiration date: September 30, 2009 Category 1 credit can be earned by reading the text material and taking this CME examination online. For complete instructions, visit the Journal’s Web site at www.jacionline.org.
The Editors thank the Baylor College of Medicine Allergy/Immunology training program for developing this CME examination. The individuals who contributed to its preparation were J. Andrew Bird, MD, Maria Garcia, MD, Niraj Patel, MD, Regina Wells, MD, Roshni Kandyil, MD, PhD, Usa Tantibhaedhyangkul, MD, Ankhi Dutta, MD, Samuel Foster, MD, Filiz Seeborg, MD, and Lenora Noroski, MD.
Learning objectives: ‘‘Novel insights from adaptor protein 3 complex deficiency’’ 1. To describe the clinical features of Hermansky-Pudlak syndrome type 2 (HPS2), which is caused by adaptor protein 3 (AP-3) deficiency. 2. To define the immune role of the AP-3 complex. 3. To define the physiopathology of the AP-3 complex.
CME items Question 1. Which clinical symptoms are associated with HPS2? A. oculocutaneous albinism, strabismus, hearing loss, and nystagmus B. oculocutaneous albinism, bleeding disorders, recurrent infections, and neutropenia C. oculocutaneous albinism, enterocolitis, and recurrent sinopulmonary infections D. oculocutaneous albinism, vision loss, recurrent infections, and hepatosplenomegaly Question 2. Which of the following is a difference between HPS2 and Chediak-Higashi syndrome? A. oculocutaneous albinism B. platelet dense bodies C. giant intracellular granules D. neutropenia
742
October 2007
Question 3. Which of the following characteristics is descriptive of patients with HPS2? A. increased susceptibility to viral infections and a more severe course with viruses such as cytomegalovirus (CMV), EBV, respiratory syncytial virus (RSV), influenza A, and parainfluenza B. intolerance of live viral vaccines with poor specific antibody response to protein and polysaccharide antigens after immunization C. dysmorphic facies and pectus deformity at birth D. presence of giant intracellular granules in neutrophils Question 4. Patients with HPS2 are more susceptible to which of the following diseases? A. Langerhans cell histiocytosis B. T-cell lymphoma C. hemophagocytic lymphohistiocytosis D. hemochromatosis
J ALLERGY CLIN IMMUNOL
Question 5. Patients with HPS2 have an absence of which subunit of AP-3? A. ß3A B. d-adaptin C. m3 D. s3 Question 6. Which of the following has been identified as a molecular mechanism for AP-3? A. targeting of lysosomal granules to the endoplasmic reticulum B. protein sorting in exocytic/endocytic pathways C. endocytosis via clathrin recruitment D. stabilization of the cell membrane Question 7. Deficiency of the ADTB3A gene in HPS2 leads to defects in which types of cells? A. cells that are erythropoietic in origin (reticuloblasts and reticulocytes) B. cells that have a large number of intracellular granules (neutrophils, NK cells, cytotoxic T lymphocytes, platelets, and monocytes) C. cells that produce B lymphocytes (plasma cells, B lymphocytes) D. cells that are found in the nervous system (oligodendrocytes, Schwann cells)
Badolato and Parolini 743
Question 8. Deficiency of the ADTB3A gene in HPS2 leads to which of the following dysfunctions at the cellular level? A. missorting of proteins such that lysosomal membrane proteins are not appropriately sorted to granules but are delivered to the plasma membrane B. truncation of proteins, resulting in loss of plasma membrane lipid complexes C. aggregation of proteins in the mitochondria, resulting in impaired ATP production D. trafficking of proteins into the ubiquitin pathway, resulting in proteolysis Question 9. Which of the following is seen with d-subunit absence of the AP-3 complex? A. cyclic pancytopenia B. deafness C. defective platelets D. lysosomal abnormalities Question 10. Melanosomes are lysosome-like organelles that are involved in the secretion of melanin and can be viewed as secretory lysosomes. In patients with HPS2, impairment of melanin synthesis by melanocytes is caused by abnormal sorting of which enzyme? A. tyrosinase B. tryptase C. lipase D. protease
Reviews and feature articles
J ALLERGY CLIN IMMUNOL VOLUME 120, NUMBER 4
Continuing Medical Education examination
Novel insights from adaptor protein 3 complex deficiency Instructions for category 1 Continuing Medical Education credit The American Academy of Allergy, Asthma & Immunology is accredited as a provider of Continuing Medical Education (CME) by the Accreditation Council for Continuing Medical Education. Test ID no.: mai00125 Contact hours: 1.0 Expiration date: September 30, 2009 Category 1 credit can be earned by reading the text material and taking this CME examination online. For complete instructions, visit the Journal’s Web site at www.jacionline.org.
The Editors thank the Baylor College of Medicine Allergy/Immunology training program for developing this CME examination. The individuals who contributed to its preparation were J. Andrew Bird, MD, Maria Garcia, MD, Niraj Patel, MD, Regina Wells, MD, Roshni Kandyil, MD, PhD, Usa Tantibhaedhyangkul, MD, Ankhi Dutta, MD, Samuel Foster, MD, Filiz Seeborg, MD, and Lenora Noroski, MD.
Learning objectives: ‘‘Novel insights from adaptor protein 3 complex deficiency’’ 1. To describe the clinical features of Hermansky-Pudlak syndrome type 2 (HPS2), which is caused by adaptor protein 3 (AP-3) deficiency. 2. To define the immune role of the AP-3 complex. 3. To define the physiopathology of the AP-3 complex.
CME items Question 1. Which clinical symptoms are associated with HPS2? A. oculocutaneous albinism, strabismus, hearing loss, and nystagmus B. oculocutaneous albinism, bleeding disorders, recurrent infections, and neutropenia C. oculocutaneous albinism, enterocolitis, and recurrent sinopulmonary infections D. oculocutaneous albinism, vision loss, recurrent infections, and hepatosplenomegaly Question 2. Which of the following is a difference between HPS2 and Chediak-Higashi syndrome? A. oculocutaneous albinism B. platelet dense bodies C. giant intracellular granules D. neutropenia
742
October 2007
Question 3. Which of the following characteristics is descriptive of patients with HPS2? A. increased susceptibility to viral infections and a more severe course with viruses such as cytomegalovirus (CMV), EBV, respiratory syncytial virus (RSV), influenza A, and parainfluenza B. intolerance of live viral vaccines with poor specific antibody response to protein and polysaccharide antigens after immunization C. dysmorphic facies and pectus deformity at birth D. presence of giant intracellular granules in neutrophils Question 4. Patients with HPS2 are more susceptible to which of the following diseases? A. Langerhans cell histiocytosis B. T-cell lymphoma C. hemophagocytic lymphohistiocytosis D. hemochromatosis
J ALLERGY CLIN IMMUNOL
Question 5. Patients with HPS2 have an absence of which subunit of AP-3? A. ß3A B. d-adaptin C. m3 D. s3 Question 6. Which of the following has been identified as a molecular mechanism for AP-3? A. targeting of lysosomal granules to the endoplasmic reticulum B. protein sorting in exocytic/endocytic pathways C. endocytosis via clathrin recruitment D. stabilization of the cell membrane Question 7. Deficiency of the ADTB3A gene in HPS2 leads to defects in which types of cells? A. cells that are erythropoietic in origin (reticuloblasts and reticulocytes) B. cells that have a large number of intracellular granules (neutrophils, NK cells, cytotoxic T lymphocytes, platelets, and monocytes) C. cells that produce B lymphocytes (plasma cells, B lymphocytes) D. cells that are found in the nervous system (oligodendrocytes, Schwann cells)
Badolato and Parolini 743
Question 8. Deficiency of the ADTB3A gene in HPS2 leads to which of the following dysfunctions at the cellular level? A. missorting of proteins such that lysosomal membrane proteins are not appropriately sorted to granules but are delivered to the plasma membrane B. truncation of proteins, resulting in loss of plasma membrane lipid complexes C. aggregation of proteins in the mitochondria, resulting in impaired ATP production D. trafficking of proteins into the ubiquitin pathway, resulting in proteolysis Question 9. Which of the following is seen with d-subunit absence of the AP-3 complex? A. cyclic pancytopenia B. deafness C. defective platelets D. lysosomal abnormalities Question 10. Melanosomes are lysosome-like organelles that are involved in the secretion of melanin and can be viewed as secretory lysosomes. In patients with HPS2, impairment of melanin synthesis by melanocytes is caused by abnormal sorting of which enzyme? A. tyrosinase B. tryptase C. lipase D. protease
Reviews and feature articles
J ALLERGY CLIN IMMUNOL VOLUME 120, NUMBER 4