Case Presentation: Alexander Kolineski, 22-year-old male organ donor. Jonathan F

Question

Case Presentation:

Alexander Kolineski, 22-year-old male organ donor.

Jonathan Forken, 35-year-old male recipient of a liver and right kidney from Mr. Kolineski. Melissa Jachowiz, 27-year-old female recipient of a pancreas and left kidney from Mr. Kolineski.

A 22-year-old man with a history of allergic reactions to peanuts was admitted to our hospital in a coma. After inadvertently ingesting satay sauce, which contains peanuts, during a Chinese meal, he had become unwell and had had a cardiorespiratory arrest that resulted in cerebral anoxia, coma, and brain death. A high level of peanut-specific IgE was detected in his serum ... multiple organs were subsequently procured. The donor's HLA phenotype was A1,24;B8,44;DRB1*03,13.

The donor's liver and right kidney were given in transplantation to a 35-year-old man, and the left kidney and pancreas were given to a 27-year-old woman. The man (HLA phenotype, A2,19;B12,-;DRB1*07,13) had end- stage renal failure.... The woman (HLA phenotype, A1,24;B8,44;DRB1*03,04) had chronic renal failure....

Both transplant recipients received immunosuppressive induction therapy with muromonab-CD3 (OKT3) and corticosteroids, azathioprine, and cyclosporine. Neither had ever had any allergy to peanuts.

Three months after transplantation, the recipient of the liver-kidney transplant reported a skin rash and laryngeal dyspnea after eating peanuts. Allergy to peanuts was diagnosed on the basis of the clinical findings; the absence of specific IgE antibodies before transplantation, their presence at the time the symptoms appeared, and their decline thereafter; and a positive basophil degranulation test.

The transfer of allergen-specific donor lymphocytes is a likely possibility.... The production of IgE by B cells depends on the presentation of allergens by antigen-presenting cells and on cooperation between B cells and regulatory T-helper lymphocytes of the Th2 type. In our patient there may have been transfer of peanut- specific IgE-producing B cells or of peanut-specific Th2 lymphocytes that induced the recipient's B cells to produce peanut-specific IgE.

Passive transfer of donor IgE is unlikely, because the half-life of IgE is only a few days, whereas the allergic reaction occurred three months after transplantation. However, we cannot rule out the possibility that donor IgE bound to the recipient's mast cells and bosophils could have persisted for more than a few days.

It is relevant that the allergy was transferred from the liver-kidney transplant, but not from the pancreas-kidney transplant. Pluripotent hematopoietic stem cells and dendritic cells are known to be normally resident in the liver. These passenger cells can migrate from the graft to the recipient's lymphoid organs, and multilineage hematopoiesis derived from donor cells can persist for several months after liver grafting.

Questions

1- What does HLA stand for? What is an HLA phenotype?

2- Why is it important to understand the "HLA phenotypes" of the individuals in this case?

3- From what you know about the structure of an antibody, explain how an IgE can be "peanut-specific."

4- One way to test for an allergy is to mix a specific allergen with basophils and mast cells from a patient

and look for "degranulation." What is occurring when these cells degranulate? How does this become a positive test for a specific allergy?

5. Why were the patients put on an immunosuppressive therapy after their transplantations?

6. Briefly describe the role of B cells and T-helper lymphocytes in immune physiology.

7- What is an "antigen-presenting cell" and what role does this type of cell play in an immune response?

8- Explain the interaction that occurs between a T-helper lymphocyte and a B cell when the B cell is

being induced to produce peanut-specific IgE. In your explanation, explain the role that the peanut allergen plays in this interaction.

9. In immediate hypersensitivity, the initial exposure to an allergen usually does not produce any symptoms. The symptoms, such as those involved in anaphylaxis, usually appear in the second exposure. What events are occurring during this initial exposure that sensitizes a person to an allergen. In your description include the role of B cells, T cells, IgE, mast cells, basophils and the allergen.

10- Describe how IgE binds and reacts with basophils and mast cells.

11- Describe the normal physiological role of a "pluripotent hemaotpoietic stem cell" in human

physiology.

12. Why is it important to note the presence of these cells in the liver when trying to understand the mechanism for how the peanut allergy was transferred to the patient?

13. In the introduction, the doctors noted well-documented transfers of allergies when bone marrow was being transplanted. Why is this a common occurrence with this type of transplant?

Explanation / Answer

HLA is human leucocyte antigen.These are cell surface proteins within chromosome which envode MHC

2-it is used to match patients and donors and to prevent rejection reaction during transplantation

3-IgE are the immunoglobulins produced in allergic conditions.I gE are specific and attach to particular type of allergen(eg-peanut)

4-when the cells degranulate,they release cytotoxic substances like proteases,histamine,seratonin which are also responsible for inflammation.

In the degranulation test,a specific allergen is injected and if inflammation occurs - the test is positive for that specific allergen.

5- To prevent rejection reaction,patients are put on immunosuppressive therapy

6-T cells are involved in cell mediated immunity and B cells in humoral immunity

7-Antigen presenting cells are those which display antigen complexed with MHC on their surface.They present the antigens to T cells

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