Cell-Mediated Immunity and Anti-HLA Antibody Tests Provide Insight to Immune Response in Renal Transplant Patients

The ImmuKnow(R) and anti-HLA antibody assays both contribute to
characterization of renal transplant patients being weaned off
immunosuppression

COLUMBIA, Md., June 1 /PRNewswire/ -- Data developed by Cylex in
conjunction with the University of Pittsburgh Medical Center, and presented
today at the American Transplantation Congress in Toronto, Canada, suggest
that cell-mediated immunity and anti-HLA antibody assays may be independent
measures of different facets of the immune response (at least in renal
transplant patients).

"Cell-mediated immunity, as measured with Cylex's ImmuKnow test, may
indicate the effectiveness of augmented immunosuppression and the risk of
viral infections," said Brad Stewart, president of Cylex. "By contrast,
levels of anti-HLA antibodies may determine the risk for antibody-mediated
rejection. In renal transplant patients who are being weaned from
immunosuppression, it seems that both assays may contribute independently
to characterize these patients."

Researchers at the University of Pittsburgh Medical Center have
independently shown that immune function, assessed using the ImmuKnow assay
for cell-mediated immunity, may correlate with decreased immunosuppression
in a cohort of renal transplant recipients enrolled in a protocol of
immunosuppression minimization using depletion induction and
monotherapy.(1) They have also determined humoral sensitization by
assessing the circulating anti-HLA antibodies.(2) The current study
("Relationship between immune function and humoral sensitization in renal
transplant recipients;" see abstract no. 974) was designed to assess the
relationship between immune function and the level of humoral sensitization
in serially matched samples.

The ImmuKnow assay of cell-mediated immunity is used to measure the
degree of immune activation of CD4+ T-cell function. Circulating anti-HLA
antibodies were determined by ELISA and expressed as percent ELISA-PRA for
anti-HLA class I and II antibodies. Immune function was determined by using
the ImmuKnow assay and ELISA-PRA in 290 samples from 39 patients receiving
renal transplantation. Samples were collected pre-treatment through 2,160
days post-treatment (mean 289 +/- 428 SD). For 33 patients, sequential
analysis (of between 4 and 14 samples per patient) also correlated with
clinical outcomes and responses to various therapies.

There was no correlation between the cell-mediated immunity (measured
in nanograms of ATP per milliliter) and percent ELISA-PRA for class I or
class II (R2 <0.1). However, the median ATP concentration of samples that
exhibited ELISA-PRA class II < 20% (n = 203) was significantly higher than
the median ATP concentration of samples (n = 87) with ELISA-PRA >20% (216
vs. 138; p = 0.0002). A similar pattern, but less significant (p = 0.07)
was observed for ELISA-PRA class I.



Three different patterns were evident among the renal transplant patients:

-- Those in whom the immune function values were in a stable zone
(100-300 ng ATP/mL) with or without anti-HLA antibodies
-- Those who exhibited diminished levels of immune function (< 100 ng
ATP/mL) following treatment for mixed forms of rejection (steroid bolus
+ plasmapheresis/IVIG + MMF) with or without a change in ELISA-PRA
-- Those who displayed low immune function (< 100 ng ATP/mL) in
association with viral infections such as BK or CMV.

About ImmuKnow(R)

ImmuKnow is an immune cell function assay that can detect cell-mediated
immunity (CMI) in adult patient populations undergoing immunosuppressive
therapy for organ transplantation, by measuring the concentration of
adenosine triphosphate (ATP) released from CD4 cells following cell
stimulation.

The ImmuKnow test is a qualitative assay and does not directly quantify
the level of immunosuppression. Results of ImmuKnow assays should be used
in conjunction with clinical presentation, medical history, and other
clinical indicators when assessing the immune status of any individual
patient. The use of the ImmuKnow assay as described in this study has not
been approved or cleared by the FDA. The company may use data from this or
similar studies to support a future FDA marketing application for a similar
indication.

About Cylex, Incorporated

Cylex(TM) is a privately held global life sciences company that is the
leader in the development and manufacture of in vitro diagnostic products
intended to illuminate immunity. ImmuKnow is the in vitro diagnostic
utilized to detect cell-mediated immunity (CMI) in patient populations
undergoing immunosuppressive therapy, and is increasingly being adopted at
organ transplant centers throughout the US and abroad. The Company's
patented technology provides an innovative platform allowing clinical
researchers to simply and reproducibly measure immune cell function for the
development of new diagnostics, biomarkers, and companion assays. The
company is based in Columbia, MD.



(1) Tan HP, Donaldson J, Basu A, et al. 411 Living donor kidney
transplants using alemtuzumab pre-conditioning and tacrolimus
monotherapy: 5 year experience. Abstract no. 137 presented at the
American Transplant Congress, Toronto, Canada, May 30, 2008.

(2) Tan HP, Donaldson J, Basu A, et al. Rejection characteristics of 200
living donor kidney transplants using alemtuzumab induction and
tacrolimus monotherapy: 3 year follow-up. Abstract no. 221 presented
at the American Transplant Congress, Toronto, Canada, May 30, 2008.




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Via: Healthcare