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TH17 deficiency in human disease
Continuing Medical Education examination
TH17 deficiency in human disease 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.: mai00245 Contact hours: 1.0 Expiration date: May 31, 2014 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 Washington University School of Medicine in St Louis Allergy and Immunology training program for developing this CME examination. The individuals who contributed to its preparation were Natalie B. Miller, MD, Sarena A. Sawlani, MD, James A. Tarbox, MD, and Jennifer M. Welch, MD, under the direction of H. James Wedner, MD.
Learning objectives: ‘‘TH17 deficiency in human disease’’ 1. To define the variety of cells capable of producing cytokines from the IL-17 cytokine family. 2. To understand TH17 development and mutations that affect maturation. 3. To describe various diseases with impaired TH17 cell differentiation that can result in susceptibility to chronic mucocutaneous candidiasis (CMC). CME items Question 1. A patient presents with recurrent infections with Candida species and Staphylococcus aureus. His mother and maternal grandmother also have similar symptoms. On the basis of laboratory data, the IgE level is increased. A mutation in what gene can lead to this presentation? A. dedicator of cytokinesis 8 (DOCK8) B. IL-12 receptor (IL12R) C. IL-23 receptor (IL23R) D. signal transducer and activator of transcription 3 (STAT3) Question 2. An infant presenting with CMC is noted to have various autoantibodies detected, which include type 1 interferons and IL-22. What likely immunodeficiency does the infant have? A. AD-HIES B. autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) C. STAT1 gain-of-function mutation D. DiGeorge syndrome Question 3. Which of the following interleukins plays a role in TH17 development? A. IL-2 B. IL-4 C. IL-6 D. IL-10
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June 2012
Question 4. In which of the following deficiencies would you see the most severe reduction in TH17 development? A. IL-12p40 deficiency B. IL-23p19 deficiency C. STAT3 deficiency D. IL-1b deficiency Question 5. A 10-year-old girl with a history of sinus infections, asthma, and shingles presents to the emergency department with dysphagia and a 15-lb weight loss. When discussing family history, her parents mention that they are first cousins. After admission to the hospital, she was found to have eosinophilia of 2000/mL on routine blood work. A mutation in which of the following genes should be suspected in this child? A. autoimmune regulator (AIRE) B. DOCK8 C. STAT3 D. STAT1 Question 6. Which of the following statements is true of TH17 T-cell development? A. IL-17A and IL-17F are produced only by TH17 and CD81 T cells. B. IL-1b is important in TH17 T-cell development but is not required. C. IL-12p40– and IL-12 receptor 1b–deficient patients have more severe reductions in TH17 populations than STAT3-deficient patients. D. IL-17A and IL-17F share the least amount of amino acid homology. J ALLERGY CLIN IMMUNOL
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 6
Question 7. Which of the following statements regarding DOCK8 mutation is true? A. Patients present with CMC. B. In vitro induction of RORgt expression by naive T cells is intact. C. RORgt levels are markedly increased in peripheral T cells. D. T-cell proliferation after activation with anti-CD3 and anti-CD28 is intact. Question 8. Of the following mutations that increase susceptibility to CMC, which is a gain-of-function mutation? A. STAT1 B. STAT3 C. IL17RA D. IL17RF Question 9. Which of the following cells produce IL-17F? A. gd T cells B. intestinal Paneth cells C. B cells D. fibroblasts
MCDONALD 1437
Question 10. Which of the following statements about thymomas is correct? A. Thymomas are associated with autoimmune manifestations, most notably with antibodies against muscle acetylcholine receptors that cause Lambert-Eaton syndrome. B. The majority of thymic epithelial cell tumors express AIRE. C. CMC is commonly associated with thymomas. D. Patients with thymomas, despite having high titers of neutralizing antibodies against IFN-a and IFN-v, do not have increased susceptibility to viral infections.
TH17 deficiency in human disease 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.: mai00245 Contact hours: 1.0 Expiration date: May 31, 2014 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 Washington University School of Medicine in St Louis Allergy and Immunology training program for developing this CME examination. The individuals who contributed to its preparation were Natalie B. Miller, MD, Sarena A. Sawlani, MD, James A. Tarbox, MD, and Jennifer M. Welch, MD, under the direction of H. James Wedner, MD.
Learning objectives: ‘‘TH17 deficiency in human disease’’ 1. To define the variety of cells capable of producing cytokines from the IL-17 cytokine family. 2. To understand TH17 development and mutations that affect maturation. 3. To describe various diseases with impaired TH17 cell differentiation that can result in susceptibility to chronic mucocutaneous candidiasis (CMC). CME items Question 1. A patient presents with recurrent infections with Candida species and Staphylococcus aureus. His mother and maternal grandmother also have similar symptoms. On the basis of laboratory data, the IgE level is increased. A mutation in what gene can lead to this presentation? A. dedicator of cytokinesis 8 (DOCK8) B. IL-12 receptor (IL12R) C. IL-23 receptor (IL23R) D. signal transducer and activator of transcription 3 (STAT3) Question 2. An infant presenting with CMC is noted to have various autoantibodies detected, which include type 1 interferons and IL-22. What likely immunodeficiency does the infant have? A. AD-HIES B. autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) C. STAT1 gain-of-function mutation D. DiGeorge syndrome Question 3. Which of the following interleukins plays a role in TH17 development? A. IL-2 B. IL-4 C. IL-6 D. IL-10
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June 2012
Question 4. In which of the following deficiencies would you see the most severe reduction in TH17 development? A. IL-12p40 deficiency B. IL-23p19 deficiency C. STAT3 deficiency D. IL-1b deficiency Question 5. A 10-year-old girl with a history of sinus infections, asthma, and shingles presents to the emergency department with dysphagia and a 15-lb weight loss. When discussing family history, her parents mention that they are first cousins. After admission to the hospital, she was found to have eosinophilia of 2000/mL on routine blood work. A mutation in which of the following genes should be suspected in this child? A. autoimmune regulator (AIRE) B. DOCK8 C. STAT3 D. STAT1 Question 6. Which of the following statements is true of TH17 T-cell development? A. IL-17A and IL-17F are produced only by TH17 and CD81 T cells. B. IL-1b is important in TH17 T-cell development but is not required. C. IL-12p40– and IL-12 receptor 1b–deficient patients have more severe reductions in TH17 populations than STAT3-deficient patients. D. IL-17A and IL-17F share the least amount of amino acid homology. J ALLERGY CLIN IMMUNOL
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 6
Question 7. Which of the following statements regarding DOCK8 mutation is true? A. Patients present with CMC. B. In vitro induction of RORgt expression by naive T cells is intact. C. RORgt levels are markedly increased in peripheral T cells. D. T-cell proliferation after activation with anti-CD3 and anti-CD28 is intact. Question 8. Of the following mutations that increase susceptibility to CMC, which is a gain-of-function mutation? A. STAT1 B. STAT3 C. IL17RA D. IL17RF Question 9. Which of the following cells produce IL-17F? A. gd T cells B. intestinal Paneth cells C. B cells D. fibroblasts
MCDONALD 1437
Question 10. Which of the following statements about thymomas is correct? A. Thymomas are associated with autoimmune manifestations, most notably with antibodies against muscle acetylcholine receptors that cause Lambert-Eaton syndrome. B. The majority of thymic epithelial cell tumors express AIRE. C. CMC is commonly associated with thymomas. D. Patients with thymomas, despite having high titers of neutralizing antibodies against IFN-a and IFN-v, do not have increased susceptibility to viral infections.