- Email: [email protected]
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: Forkhead box protein 3 mutations and lack of regulatory T cells
Reviews and feature articles
Continuing Medical Education examination
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: Forkhead box protein 3 mutations and lack of regulatory T cells 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.: mai00126 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 University of South Florida Division of Allergy/Immunology training program for developing this CME examination. The individuals who contributed to its preparation were Panida Sriaroon, MD, Jason W. Caldwell, DO, and Morna J. Dorsey, MD, MMSc.
Learning objectives: ‘‘Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: Forkhead box protein 3 mutations and lack of regulatory T cells’’ 1. To recognize the main clinical manifestations of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and differentiate between it and other primary immune deficiency disorders. 2. To recognize laboratory parameters associated with IPEX. 3. To understand the molecular basis of forkhead box protein 3 (FOXP3) mutations in IPEX and the function of regulatory T cells (Tregs). 4. To recognize the current treatment modalities for IPEX.
CME items Question 1. Most patients with IPEX present with a basic clinical triad of — A. recurrent infection, encephalopathy, and enteropathy. B. enteropathy, endocrinopathy, and dermatitis. C. endocrinopathy, candidiasis, and hypogonadism. D. immune thrombocytopenic purpura, adenopathy, and splenomegaly. Question 2. Which of the following statements about the characteristic features of IPEX is true? A. The gastrointestinal disease of IPEX is characterized by severe villous atrophy and extensive lymphocytic infiltrates of bowel mucosa. B. Autoantibodies are not frequently demonstrated in autoimmune hematologic disorders of patients with IPEX. C. Hypothyroidism is the most common endocrine disorder associated with IPEX. D. Kidneys are rarely affected in IPEX. J ALLERGY CLIN IMMUNOL
Question 3. Other than the endocrine manifestations, FOXP3 mutations yield immune deficiency leading to sepsis, meningitis, pneumonia, and osteomyelitis. Which of the following sets of organisms are reported in the article to be the most common? A. enterococcus, Staphylococcus species, cytomegalovirus (CMV), Candida B. encapsulated organisms C. enteric pathogens D. Aspergillus, CMV, adenovirus, and Epstein-Barr virus Question 4. Which of the following laboratory value(s) would be expected in a patient with IPEX? A. low CD41 T cells B. normal T-cell and B-cell subset with low T-cell proliferative responses C. elevated serum IgE D. undetectable serum IgA
October 2007
751
752 Torgerson and Ochs
Reviews and feature articles
Question 5. The human FOXP3 gene — A. is located on the long arm of the X chromosome. B. is expressed predominantly in the gastrointestinal tract and bone marrow. C. can be inducibly expressed by activated B cells. D. functions as the master regulator in the development and function of Tregs. Question 6. FOXP3 is a transcription factor that is mutated in patients with IPEX. Which of the following domains is required for nuclear transport and DNA binding? A. leucine zipper B. proline-rich domain C. forkhead domain D. a hydrophobic domain Question 7. Tregs are characterized by which of the following markers? A. CD41, FOXP31, CD252 B. CD31, CD82, CD42, FOXP31 C. CD41, FOXP31, IL-2 receptor a1 D. CD41, FOXP3, CD45RO1
J ALLERGY CLIN IMMUNOL OCTOBER 2007
Question 8. Which of the following statements about Tregs is correct? A. Upon activation, Tregs suppress the proliferation of naı¨ve and memory T cells. B. Tregs play a small or no role in transplantation tolerance. C. Patients with chronic graft versus host disease following bone marrow transplantation have increased numbers and expression of FOXP3 in Tregs. D. Decreased number and activity of Tregs have been associated with tumor progression. Question 9. Which of the following conditions has been reported to cause IPEX-like syndrome? A. CD25 deficiency B. CD40 ligand deficiency C. mutation in recombinase activating gene 1 D. uracil-DNA glycosylase deficiency Question 10. Once the diagnosis of IPEX is confirmed, which of these therapeutic options should be considered? A. intravenous immunoglobulin (IVIG), splenectomy B. IVIG, peripheral leukocyte infusion C. preventive antibiotics and IFN-g D. stem cell transplantation
Continuing Medical Education examination
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: Forkhead box protein 3 mutations and lack of regulatory T cells 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.: mai00126 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 University of South Florida Division of Allergy/Immunology training program for developing this CME examination. The individuals who contributed to its preparation were Panida Sriaroon, MD, Jason W. Caldwell, DO, and Morna J. Dorsey, MD, MMSc.
Learning objectives: ‘‘Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: Forkhead box protein 3 mutations and lack of regulatory T cells’’ 1. To recognize the main clinical manifestations of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and differentiate between it and other primary immune deficiency disorders. 2. To recognize laboratory parameters associated with IPEX. 3. To understand the molecular basis of forkhead box protein 3 (FOXP3) mutations in IPEX and the function of regulatory T cells (Tregs). 4. To recognize the current treatment modalities for IPEX.
CME items Question 1. Most patients with IPEX present with a basic clinical triad of — A. recurrent infection, encephalopathy, and enteropathy. B. enteropathy, endocrinopathy, and dermatitis. C. endocrinopathy, candidiasis, and hypogonadism. D. immune thrombocytopenic purpura, adenopathy, and splenomegaly. Question 2. Which of the following statements about the characteristic features of IPEX is true? A. The gastrointestinal disease of IPEX is characterized by severe villous atrophy and extensive lymphocytic infiltrates of bowel mucosa. B. Autoantibodies are not frequently demonstrated in autoimmune hematologic disorders of patients with IPEX. C. Hypothyroidism is the most common endocrine disorder associated with IPEX. D. Kidneys are rarely affected in IPEX. J ALLERGY CLIN IMMUNOL
Question 3. Other than the endocrine manifestations, FOXP3 mutations yield immune deficiency leading to sepsis, meningitis, pneumonia, and osteomyelitis. Which of the following sets of organisms are reported in the article to be the most common? A. enterococcus, Staphylococcus species, cytomegalovirus (CMV), Candida B. encapsulated organisms C. enteric pathogens D. Aspergillus, CMV, adenovirus, and Epstein-Barr virus Question 4. Which of the following laboratory value(s) would be expected in a patient with IPEX? A. low CD41 T cells B. normal T-cell and B-cell subset with low T-cell proliferative responses C. elevated serum IgE D. undetectable serum IgA
October 2007
751
752 Torgerson and Ochs
Reviews and feature articles
Question 5. The human FOXP3 gene — A. is located on the long arm of the X chromosome. B. is expressed predominantly in the gastrointestinal tract and bone marrow. C. can be inducibly expressed by activated B cells. D. functions as the master regulator in the development and function of Tregs. Question 6. FOXP3 is a transcription factor that is mutated in patients with IPEX. Which of the following domains is required for nuclear transport and DNA binding? A. leucine zipper B. proline-rich domain C. forkhead domain D. a hydrophobic domain Question 7. Tregs are characterized by which of the following markers? A. CD41, FOXP31, CD252 B. CD31, CD82, CD42, FOXP31 C. CD41, FOXP31, IL-2 receptor a1 D. CD41, FOXP3, CD45RO1
J ALLERGY CLIN IMMUNOL OCTOBER 2007
Question 8. Which of the following statements about Tregs is correct? A. Upon activation, Tregs suppress the proliferation of naı¨ve and memory T cells. B. Tregs play a small or no role in transplantation tolerance. C. Patients with chronic graft versus host disease following bone marrow transplantation have increased numbers and expression of FOXP3 in Tregs. D. Decreased number and activity of Tregs have been associated with tumor progression. Question 9. Which of the following conditions has been reported to cause IPEX-like syndrome? A. CD25 deficiency B. CD40 ligand deficiency C. mutation in recombinase activating gene 1 D. uracil-DNA glycosylase deficiency Question 10. Once the diagnosis of IPEX is confirmed, which of these therapeutic options should be considered? A. intravenous immunoglobulin (IVIG), splenectomy B. IVIG, peripheral leukocyte infusion C. preventive antibiotics and IFN-g D. stem cell transplantation