Clinical trial NCT01334281: An In-vitro Standardization of B Cell Elispot Assays
Official title: A Phase 1, Investigatory Initiated, In-vitro Standardization of B Cell Elispot Assays
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Transplant Sensitization
Panel Reactive Antibody
Sensitization to HLA Antigens
Keywords: Panel Reactive Antibody (PRA)
Sensitization
Organ Transplant
Lead sponsor: Northwestern University
Sponsor class: OTHER
First posted: 2011-04-13
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Any kidney, pancreas or heart transplant waitlisted subjects \> or = to 18 years of age, and of either gender. Subjects must be capable of understanding the study, informed consent form, HIPPA process, and be willing to give informed consent.

Brief summary: This study is being done because the study doctor is trying to develop a new test which will help transplant doctors monitor patients with high panel reactive antibodies (PRA). The test would be used to monitor patients' PRA when doctors are trying to lower it through a process known as desensitization. Desensitization lowers high PRA levels and allows patients to receive transplants. This is a single center study to evaluate and optimize the use of a new laboratory test to detect and measure the immune system's functioning.

Detailed description: Sensitization to HLA antigens is the main barrier to solid organ transplantation. Currently, HLA sensitization is monitored by testing patients' serum against a panel of HLA antigens (whether those will be presented on cell surface or on solid phase matrixes) and calculating the % of positive responses. Such result give indication of the relative breadth of sensitization but not on it "depth" - the relative strength of specific antibodies, nor does it provide any information regarding the memory B cells / plasma cells that can manufacture a specific HLA directed antibody.

This is a single center study to evaluate and optimize the use of in-vitro assay to enumerate B cells producing human leukocyte antigens (HLA)-specific antibodies. The proposed assay is based on principles used for enumeration of specific cytokine producing memory T cells - an ELISPOT assay. The investigators are currently using the T cell ELISPOT assay in our laboratory.

The investigators believe that the proposed assay will provide biologically relevant immune measures that are crucial for the long term outcome of transplantation in highly sensitized patients.

Highly sensitized patients encompass a high risk patient group among transplant recipients. The proposed assay is designed to predict the fate of DSA producing (or capable of producing) memory and plasma cells. Thus, it should allow prediction and early detection of activation of the humoral arm of the immune system, specifically against the donor. This, in turn, may prompt early intervention and preservation of the allograft. Three tubes of blood will be drawn twice, 8-12 weeks apart, during clinic or standard of care dialysis visits following optimization. Subjects undergoing desensitization will have three tubes of blood drawn seven times over the course of two years for the analysis.

Eligibility criteria: Inclusion Criteria:

* Subjects should be listed for solid organ transplant at NU/NMH
* Subjects should be \> or = to 18 years of age, either gender
* Subjects should have history of prior sensitization of HLA antigens
* Subjects should have documented antibody specificity previously tested at the transplant immunology lab at NU
* Subjects should be capable of understanding the study, consents, HIPAA process and be able to give informed consent.

Exclusion Criteria:

* Subjects younger than 18 years of age
* Subjects with no sensitization history

Primary outcomes:
measure: To optimize an in-vitro assay to enumerate HLA-specific memory B cells in order to monitor efficacy of desensitization protocols.
timeFrame: Enrollment (baseline), midpoint of desensitization (only if receiving high dose IVIg); prior to transplant; 3, 6, 12 and 24 months post-transplant.
Secondary outcomes:
measure: Evaluate the relationships between antibody strength, measured by flow cytometry, number of memory B cells in circulation of highly sensitized patients awaiting organ transplant or undergoing desensitization procedures to facilitate organ transplant.
timeFrame: Enrollment (baseline), midpoint of desensitization (only if receiving high dose IVIg); prior to transplant; 3, 6, 12 and 24 months post-transplant.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
Study officials:
affiliation: Northwestern University
name: Anat Tambur, DMD, PhD
role: PRINCIPAL_INVESTIGATOR
References: