# Presentation: 859025

## CDER Meeting: Surrogate Markers of Immunity

**Presenter: Judith A. Britz, Ph.D.**
**October 16, 2000**

## Slide 2

## HIV Pathogenesis 

**Cellular Immune Function Tests have Prognostic Value:**
- independent of CD4+ Count
- Up to 1 year before CD4 Count Decline
**Progressive Loss of Function as measured by response to:**
- Mitogens
- Alloantigens
- Recall Antigens

**Clerici et al. 1989. **_**J. Clin. Invest.**_** 84: 1892**
**Dolan et al. 1995. **_**J. Infect. Dis.**_**172:79**

## Immune Reconstitution

**LPA Reactivity to HIV p24 rAg enhanced:**
- Long Term Non-Progressors
- Following early treatment of acute HIV  infection
- Strengthened by treatment interruption (in some patients)

**Rosenberg, E.S et al. 1997. **_**Science**_** 278: 1447**
**Rosenberg, E.S. et al. 2000. **_**Nature**_** 408: 523**

## Lymphoproliferation (LPA)

**Traditional method for evaluating **
**cell-mediated immune function: **
**Time-consuming: 5-7 Days**
**Radioactive**
**Labor-intensive**
**Not widely available**
**Not standardized**
**Shipping impact**
**Not practical for clinical use**

**Betensky et al. 2000. Clin. Diag. Lab. Immunol. 7(5): 759**

##                               Objectives

**Clinical Correlate of Cell-Mediated Immunity**
**24 Hours or less**
**Non-Radioactive**
**Whole Blood or PBMCs**
**Cost Effective**
**Adaptable to Test with Multiple Antigens**
**Standardized**

## Lymphocyte

- Stimulation

- 4 hours to overnight

## Comparison with LPA

**DPM x 100**
**LPA assay 96 HRS**

**ATP ng/mL**
***In vitro *****CMI Overnight**

## Reference

**	****Sottong, P.R., J.A. Rosebrock, J.A. Britz, and T.R. Kramer. 2000. **
**	****Measurement of T-lymphocyte responses in whole blood cultured using newly synthesized DNA and ATP. **
**	**_**Clinical and Diagnostic Laboratory Immunology**_** 7(2): 307-311**

## PHA Distribution of Normal and HIV+ Patients

**Normal**

**HIV+**

- Homi Farzadegan. Johns Hopkins. 2000. IHV Meeting.

##  Measurement Of Cell Activation By Mitogens And Recall Antigens 

** ****Measurement Of Cell Activation By Mitogens And Recall Antigens**** **

- Therapy Changed

- B.J. Loechelt, M. Chan  Children’s National Medical Center, Washington, D.C; 2000. Manuscript in Preparation.

**Notes:**
Longitudinal study

##  Measurement Of Cell Activation By Mitogens And Recall Antigens 

** ****Measurement Of Cell Activation By Mitogens And Recall Antigens**** **

- B.J. Loechelt, M. Chan  Children’s National Medical Center, Washington, D.C; 2000. Manuscript in preparation

**Notes:**
Longitudinal study

## ATP

- Cunningham-Rundles, S. and J. Cervia. Cornell University School of Medicine. 2000. Manuscript in preparation.

## Wahren, B. et al. Karolinska Institute. 2000. IHV Meeting

## Lymphocyte Response

- Lymphocyte
- Stimulation

**ATP**
**1/2 - 6 hours**

**Cylex              *****In Vitro *****CMI**

**Cytokine Assays**

**Lympho-proliferation**

## Analytical Parameters

**Accuracy**
**Precision**
**Sensitivity**
**Specificity**
**Reproducibility**
**Stability**
**Standardization**

## AIDS Patient Management

## Acknowledgements

**Susanna Cunnigham-Rundles: Cornell**
**Brett Loechelt: George Washington**
**Homi Farzadegan: Johns Hopkins**
**Britta Wahren: Karolinska**
**Tim Kramer: USDA**
**Peter Sottong: Cylex**
**Richard Kowalski: Cylex**
**Julie Woodcock: Cylex**