Afzal Nikaein

CD30, a marker to detect the high‐risk kidney transplant recipients

Abstract:u2002Background:u2002 Sensitization of potential renal transplant recipients may impact the selection of donors and the outcome of transplant. Another element of the potential kidney transplant recipient immune system that provides useful information regarding the transplant outcome is the immunologic CD30 molecule.

Clinically irrelevant circulating human leukocyte antigen antibodies in the presence of ventricular assist devices.

INTRODUCTIONnIdentification of anti-human leukocyte antigen (HLA) antibodies by single-antigen beads (SAB) allows for prediction of donor-specific crossmatches (virtual crossmatches), thus facilitating the allocation of organs from deceased donors. However, the clinical relevance of HLA antibodies identified by SAB has been less than clear. This study demonstrates that sera from cardiac transplant candidates with a ventricular assist device (VAD) or infection may contain clinically irrelevant antibodies that bind to the beads but not to lymphocytes.nnnMETHODSnInvestigated were 5 cardiac transplant candidates (3 with VAD, all with infections, and 1 retransplant) with positive HLA antibodies detected by SAB, but negative by cytotoxicity. To determine clinical relevance of the antibodies, flow cytometric crossmatches (FCXM) were performed. Untreated beads and elution buffer-treated beads to dissociate the β-2 microglobulin and the peptide from the heavy chain were used.nnnRESULTSnThe virtual crossmatch data were compared with data from actual FCXMs. Of 40 T-cell and B-cell FCXM, SAB-identified HLA antibodies were predictive for only 1 T-cell and 9 B-cell FCXM outcomes. Patients sera contained a mixture of antibodies directed against cryptic epitopes on the heavy chain and exposed epitopes. The mean fluorescence intensity of antibodies varied from 1,040 to 11,000.nnnCONCLUSIONSnSera from cardiac transplant candidates with or without VAD may contain natural antibodies that do not bind to intact antigens on the cell surface. Therefore, great care must be exercised before denying a life-saving transplant to these patients simply on the basis of SAB results.

Pre‐transplant level of soluble CD30 is associated with infection after heart transplantation

Abstract:u2002Background:u2002 One immunologic element of the immune system is the CD30 molecule which belongs to the TNF‐R superfamily. CD30 can serve as a T‐cell signal transducing molecule and is expressed by a subset of activated T lymphocytes, CD45RO+ memory T cells. Augmentation of soluble CD30 during kidney transplant (Tx) rejection has been reported. Our study was to determine if the level of sCD30 prior to heart transplant (HTx) could categorize the patients (pts) into high or low immunologic risk for post‐Tx outcome.

Development of class I-specific helper-inducer T-cell clone.

A unique alloreactive human helper-inducer T-cell clone which reacts with the class I HLA antigen was characterized. The clone was derived from a mixed lymphocyte culture between cells from a HLA-A2-; B35,w51; Bw4,Bw6; Cw4,-; DR1,4; DQw1,-; DRw53 responder and a HLA-A2,3; B7,14; Bw6; Cw8,-; DR7,-; DQw2,w3; DRw52 stimulator. When screened against a panel of stimulator cells, this clone was found to have a specificity towards a stimulator HLA-B14 and consisted entirely of Leu-4, Leu-3, and 4B4 positive T cells, which is a T helper-inducer phenotype. Using monoclonal antibodies directed towards various monomorphic class I and II HLA epitopes in an inhibition experiment, it was found that both monoclonal antibodies w6/32 and 4E (recognizing class I monomorphic and HLA-B epitopes, respectively) inhibited proliferation. However, monoclonal antibodies BBm.1 and L227 (directed against beta 2-microglobulin and Ia-like molecule, respectively) had no inhibitory effect. Functional evaluation of this clone demonstrated helper activity on the proliferation of MLC response. The helper-induction effect on MLC cultures remained intact following irradiation of the clone for either 500 or 2000 rad suggesting that helper function of the clone was radiation resistant. The helper activity of this clone was MHC nonrestricted since it enhanced proliferation of the original responder and stimulator MLC as well as third and fourth party individuals. By CTLL cell line proliferation assay, this clone was found to release IL-2. When assayed (day 1 to 7) for class II HLA products expression following stimulation, HLA-DRw53 was consistently expressed by the clone. However, HLA-DR1, DQw1 were found to be expressed simultaneously on day 2 through day 7 and HLA-DR4, DQw3 on day 2 and 3. These data demonstrate, for the first time, the generation of a class I specific helper-inducer T-cell clone in MLC response.