PHRM641

Case 16

Part 2 – Excess Inflammation

Dr. Rhodes prescribes ganciclovir and IVIG therapy for Jude to try to control the EBV infection. She is
concerned about Jude’s worsening condition and indications that his liver function is failing rapidly. She
performs a bone marrow aspiration and examines the bone marrow cells by microscopy and flow cytometry.
She also performs flow cytometry on his blood lymphocytes and ELISA on his blood serum to quantitate the
levels of several cytokines.

Jude he has abnormally high numbers of CD8+ T cells in his blood which express the activation marker CD56.
Consistent with high numbers of activated T cells and the inflammatory damage being done to Jude’s liver, his
serum shows high levels of IFN-gamma, IL-6 and TNF-alpha. Jude’s bone marrow is hypocellular and the cells
that are present are mostly atypical B cells, and CD8+ T cells. The bone marrow also shows many macrophages
that are showing signs of activation and hemophagocytic activity.

Dr. Rhodes now suspects that Jude is suffering from hemophagocytic lymphohistiocytosis (HLH). He is
immediately placed on aggressive immunosuppressive therapy with dexamethasone and rituximab which
eventually are able to resolve the EBV infection and allowed Jude to recover.

Questions:
1. What cells are secreting IFN-gamma in this scenario? What cells are being activated by the IFN-
gamma? How does this activation contribute to the inflammation in this case?
2. Can you think of a therapeutic strategy that might control this inflammation?
(Hint: remember from the WHIM syndrome case that you can use drugs to block the interaction of
cytokines with their receptors)
3. What are the CD8+ T cells probably recognizing in this case?
4. Why do you think Dr. Rhodes added rituximab to Jude’s therapy?