Allergy and Immunology Review Corner: Chapter 21 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD.

Transcription

1 Allergy and Immunology Review Corner: Chapter 21 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Chapter 21: Transplantation Immunity and Clinical Applications Prepared by Bob Geng, MD, UCLA, and Monica Bhagat, MD, University of Pennsylvania 1. Thalidomide is an old drug that has been rediscovered to have a new function in the treatment of multiple myeloma. There are multiple proposed mechanisms of the action of Thalidomide. Which of the following is NOT a likely mechanism of action? A. Inhibition of myeloma cell adhesion to bone marrow stromal cells B. Blocking of Il-6, TNF-alpha, and IL-1beta secretion from bone marrow stromal cells C. Inhibition of VEGF and Beta-FGF in the stimulation of bone marrow neovascularization D. Induction of IL-2 and IFN-gamma release from T-cells E. Acts as a intracellular proteasome inhibitor for myeloma cells 2. A patient diagnosed with multiple myeloma would like to know his prognosis of survival. His serum calcium is 12 g/dl, Hemoglobin is 9.5 g/dl, serum beta-2 microglobulin is 6 mg/l, and his albumin is 2.5 g/dl. According to the latest International Staging System (ISS), what is his approximate average length of survival? A. 3 years B. 62 months C. 44 months D. 29 months E. 2 months 3. A patient diagnosed with Monoclonal Gammopathy of Undetermined Significance (MGUS) is inquiring about his risk of progressing to Multiple Myeloma. Which of the following features would not suggest a greater risk of progression? A. Serum free kappa/free lambda ratio of 1.8 B. Urine free kappa/free lambda ratio of 5 C. Serum free kappa/free lambda ratio of 0.2 D. Urine free kappa/free lambda ratio of 0.3 E. Serum free kappa/free lambda ratio of 1 F. Presence of circulating myeloma plasma cells. 4. Rituximab is an anti-cd20 monoclonal antibody that has been used for the treatment of lymphoma and various autoimmune disorders. Which of the following stages of B cell development does Rituximab NOT target? A. Mature B cell B. Germinal Center B cell C. Memory B cell D. Plasma cell E. Immature B cell

2 F. Pre B cell G. Choices A and C H. Choices D and E I. Choices F and D J. Choices C and F K. Targets all stages. 5. A patient has recently been diagnosed with Hodgkin s Lymphoma, and received a lymph node biopsy that is being processed for staining of specific cell surface markers. On typical H&E stain you notice many bilobed nuclei cells that have a distinct owl s eye appearance. What would you predict would be the pattern of immunohistologicstaining of cell surface markers expressed on those particular cells? A. CD30+/CD15+/CD20+/CD45+ B. CD30-/CD15+/CD20-/CD45+ C. CD30+/CD15+/CD20-/CD45- D. CD30+/CD15-/CD20+/CD45- E. CD30-/CD15-/CD20-/CD45-6. In protein electrophoresis, which of the following conditions may result in an abnormal elevated gamma globulin pattern? A. Cirrhosis B. Chronic infection C. Various autoimmune diseases D. All of the above 7. Which of the following statements regarding smoldering multiple myeloma (SMM) is FALSE? A. Associated with a lower probability of evolving to MM when compared to MGUS B. Serum M protein is > or equal to 3 g/dl C. Bone marrow plasma cells > or equal to 10 percent D. Absence of anemia, hypercalcemia, lytic bone lsions, renal insufficiency 8. Reed-Sternberg (RS) cells are large and are either multinucleated or have a bilobed nucleus. RS cells may be found in which of the following conditions? A. Classical Hodgkin s lymphoma B. Non-Hodgkin s lymphoma (rarely) C. Mononucleosis D. Drug-induced reactive lymphadenopathy E. All of the above 9. Each of the following are examples of techniques used to diagnose the monoclonal gammopathies EXCEPT: A. Immunoelectrophoresis B. Immunofixation C. Determination of urinary protein D. FISH assays

3 E. Determination of relative amounts of kappa and lambda chains 10. POEMS is NOT characterized by which of the following? A. Peripheral neuropathy B. Endocrinopathy C. Thrombocytopenia D. Association with Castleman s disease Answers 1. E, pages See Figure D, pages See Table E, pages See Table Higher incidence of MM occurs in those patients with abnormal ratio of either < 0.26 or > I, pages See Figure C, page 855. See Figure D, pages Hypergammaglobulinemia is a non-specific finding that may be due to a broad differential of conditions. The classic M spike is present in patients with multiple myeloma due to a restricted increase of a monoclonal immunoglobulin product (single clone). Of note, this M component may be either an intact immunoglobulin (IgA, IgG, IgD, or IgE) or a Bence-Jones protein (free kappa or free lambda chains). 7. A, pages SMM is associated with a HIGHER probability of evolving to MM when compared to MGUS. 8. E, pages HL is a B cell neoplasm characterized by a minority of neoplastic cells, the RS cells, which are located within an extensive infiltrate of reactive cells. Although necessary for the diagnosis of HL, it is not sufficient, and RS cells are actually also present in other conditions, as listed above. They are RARELY found in NHL. 9. D, pages FISH assays are used to diagnose lymphoproliferative disorders and are used to search for specific chromosomal abnormalities in the DNA of interphase cells. 10. C, page 840. Box 21-4 Suspicion for POEMS should be raised in the setting of thrombocytosis and sclerotic bone lesions on plain radiographs.

4 Allergy and Immunology Review Corner: Chapter 22 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Chapter 22: Transplantation Immunity and Clinical Applications Prepared by Monica Bhagat, MD, University of Pennsylvania, and Marissa Shams, MD, Emory University 1. Which of the following types of immune cells are cytopathic and facilitate graft rejection? A. Th1 cells B. Th17 cells C. A and B D. Treg cells 2. In solid organ transplantation, the degree of HLA compatibility is described in terms of the number of mismatches at which of the following particular histocompatibility antigens? A. ABO antigens only B. HLA-A, HLA-B, and HLA-DR antigens C. HLA-DR, HLA-DQ, and HLA-DP antigens D. HLA matching is no longer critical for solid organ transplantation 3. In hematopoietic stem cell transplantation (HSCT), which of the following sources of stem cells is typically associated with slower engraftment? A. Peripheral blood stem cells B. Bone marrow C. Umbilical cord of newborn babies D. All of the above 4. Which of the following monoclonal antibodies are chimeric in nature and bind to the IL-2 receptor on T cells? A. Basiliximab B. OKT3 C. Basiliximab and Daclizumab D. Rituximab 5. Minor histocompatability antigens (mha) are which of the following: A. Immunogenic peptides from polymorphic exogenous cellular proteins B. Incapable of triggering an immune reaction and are harmless C. Known to play a role in GVHD D. Known to induce a strong T cell response when multiple mha mismatches are present E. A&B

5 F. C&D 6. True or False: For HSC (hematopoietic stem cell) Transplant; allele matching occurs only at HLA-A, HLA-B, HLA-C. 7. The most reliable means of detection for acute rejection: A. HLA typing with CDC (complement dependent lymphotoxicity) B. Percutatenous needle biopsy of the graft C. PRA (Percentage reactive to Antibody) D. CBC with differential and lymphocyte enumeration 8. Which of the following individuals are most at risk for development of acute Graft- Versus-Host Disease (GVHD)? A. Recipients of HSC transplant B.. Recipients of small bowel transplant C.. Immune compromised patient reeiving non-irradiated blood transfusions D. None of the above E. All of the above 9. Mononuclear cell infiltration, fibrosis and scarring of parenchyma and associated blood vessels is associated with: A. Acute Rejection B. Hyperacute Rejection C. Delayed Rejection D. Chronic Rejection 10. Matching a prospective patient in need of solid organ transplant with prospective donor includes all of the following steps, EXCEPT: A. Identification of patient s HLA haplotypes via Complement-dependent lymphocytoxicity (CDC) assay or commercially available HLA-typing trays using purified B and T lymphocytes B. Screening for potential HLA antibodies in the recipient s serum directed toward any of the donors HLA haplotype. C. ABO typing and crossmatching of donor and recipient for detection and ABO incompatibility. D. Desensitization of a mismatch anti-hla antibody present in recipient serum against donor HLA haplotypes with plasmapharesis and IVIG Answers 1. C, page 869, Fig 22-4 Organ engraftment is promoted by a balanced Treg/effector cell ratio preventing the destructive effects of Th1, Th2, and Th17 cells that mediate graft rejection. Therapies aim to promote the function of the immunosuppressive Treg cells post-transplantation. 2. B, pages

6 Histocompatibility antigens include the major blood group antigens, HLA antigens, and a variety of minor histocompatibility antigens. For solid organ transplants, we focus on the number of mismatches at HLA-A, HLA-B, and HLA-DR antigens ONLY (C, DQ, and DP are ignored). So, overall this means a perfect match is called a zero antigen mismatch and the opposite scenario is known as six-antigen mismatch. Also, although modern treatments have made it possible to completely suppress the recipient s system (making HLA matching less critical), there is better outcomes in well-matched transplants! 3. D, pages Umbilical cord source provides rapidly available stem cells and less chance of rejection with transplantation due to immaturity of cells. The main disadvantage of utilizing this source is lack of adequate cell dose for larger patients and slower engraftment. 4. C, pages Both of these are chimeric mouse-human monoclonal antibodies that bind to the IL-2 receptor on T cells, leading to saturation of the IL-2 receptors and prevents T cell activation. OKT3 is specific for the T cell marker CD3 but may lead to cytokine release storm and late post-transplant lymphoproliferative disorder. Rituximab is a murine/human monoclonal antibody directed against CD20 antigen on the surface of normal and malignant B lymphocytes. 5. F, page 872 mha are immunogenic peptides from polymorphic endogenous cellular proteins. These proteins are present in different allelic forms in different individuals. In the transplant setting, individual mha mismatches between donor and recipient trigger a weak immune response. However, multiple mismatches can induce a strong T cell response. 6. FALSE page 872 For HSCT transplant, allele matching occurs at HLA-A, HLA-B, HLA-C, HLA-DRß1 & HLA-DQß1. A perfect match for HSC transplant occurs with 10/10 alleles matching. In comparison, Solid Organ Transplant allele matching occurs at HLA-A, HLA-B, HLA-DR and a perfect match occurs with 6/6 alleles matching. 7. B, page 874 The risk of acute rejection of solid organ transplant is highest in the first 3 months after transplantation and manifests as a sudden decline in graft function. The most reliable method for diagnosis of acute rejection is percutaneous needle biopsy of the allograft. Many factors may contribute to the development of acute rejection including; degree of HLA-mismatch, retransplantation, reactive anti-hla antibody, antibody specificity for donor HLA antigens. 8. E, page 876 Although GVHD is most commonly a complication of HSC transplant, other groups are at risk including recipients of small bowel transplant and any immune compromised patient receiving non-irradiated blood transfusions. The primary targets of acute GVHD are skin, liver and intestinal tract.

7 9. D, page 876 Chronic Rejection typically develops months to years after transplantation with gradual loss of graft function. On histopath examination there is mononuclear infiltration with both Bcells and Tcells. Examples include Vanishing Bile Duct Syndrome in the liver transplant and Bronchiolitis Obliterans with lung transplant. 10. D, page 880 Many transplant centers have developed protocols to temporarily desensitize patients in order to create a window of opportunity during which anti-hla antibody titers are reduced low enough where a transplant be undertaken without the risk of hyperacute rejection. However, this procedure is usually reserved for patients previously sensitized to HLA-antigens (via pregnancy, prior transplant or transfusion) requiring solid organ transplantation with deteriorating clinical condition and no other suitable match. Additionally, this procedure is not a component of the routine screening algorithm for histocompatability testing.