Cryptococcal Capsule and IRIS

Darin L Wiesner

Healthy Response To Cryptococcus

Normal

Adapted from Wiesner and Boulware, Curr Fungal Infect Rep 2011

Healthy Response To Cryptococcus

Normal

Adapted from Wiesner and Boulware, Curr Fungal Infect Rep 2011

Healthy Response To Cryptococcus

Normal

Adapted from Wiesner and Boulware, Curr Fungal Infect Rep 2011

Theory of CM-IRIS Pathogenesis

Adapted from Wiesner and Boulware, Curr Fungal Infect Rep 2011

Pathologic

Hypothesis:

• CM Patients that mount an ineffective ex vivo cytokine response to cryptococcal capsular antigen are at increased risk for death or IRIS.

45%

20%

35%

Patient Characteristics

CM Only

CM-IRIS

Death

Ineffective Response

Normal Response

45%

20%

35%

Patient Characteristics

CM Only

CM-IRIS

Death

Ineffective Response

Normal Response

Cytokine Response to Capsular Antigen

Equivalent

Significantly Elevated

Cytokine Response Relativeto Negative Control:

Multivariate Model of IRIS/Death Risk

Theory of CM-IRIS Pathogenesis

Adapted from Wiesner and Boulware, Curr Fungal Infect Rep 2011

Pathologic

Acknowledgements• Mentorship:

– David Boulware, U of MN– Paul Bohjanen, U of MN– Kirsten Nielsen, U of MN

• Reagents and/or Discussion:– Stu Levitz, U of MA– Nielsen Lab, U of MN– Mellissa Rolfes, U of MN

• Clinic:– David Meya, IDI - Kampala– Andrew Kumbugu, IDI – Kampala

• Laboratory:– Henry Kajambula, Makerere U– Andrew Akampurira, Makerere U– Beatrice Achan, Makerere U