Serum rejection

The finding that the administration of 6-mercaptopurine to rabbits following exposure to bovine serum albumin prevented antibody formation [374] formed the basis for a new area of chemotherapy for purine analogues and other antimetabolites and was soon followed by the use of these drugs for the therapy of autoimmune disease and the suppression of homograft rejection. This subject has been reviewed in depth [ 12, 375, 375a], has occasioned a symposium [376], and has received much recent publicity as a result of human heart transplants. 

This includes patients with Banff grade II acute rejection or vascular rejection prior to cyclosporine withdrawal, those who are dialysis-dependent, or with serum creatinine greater than 4.5 mg/dL, black patients, retransplants, multi-organ transplants, or patients with high panel of reactive antibodies. 

Elevated BUN and serum creatinine It is not unusual for serum creatinine and BUN levels to be elevated during cyclosporine therapy. These elevations in renal transplant patients do not necessarily indicate rejection, and each patient must be fully evaluated before dosage adjustment is indicated. These increases reflect a reduction in the glomerular filtration rate. Impaired renal function at any time requires close monitoring, and frequent dosage adjustments may be indicated. The frequency and severity of serum creatinine elevations increase with dose and duration of cyclosporine therapy. These elevations are likely to become more pronounced without dose reduction or discontinuation. 

Anti-lymphocyte globulin (ALG) has been prepared as an highly purified solution of y-globulins with antilymphocyte activity by immunizing horses with human lymphocytes. It activates complement-mediated destruction of lymphocytes and thus decreases cellular immunity with only a limited effect on humoral immunity. Anti-lymphocyte globulin suppresses delayed type hypersensitivity reactions. It is used for the prevention and treatment of rejection episodes of transplanted organs. It also has some indication for the management of idiopathic aplastic anemia. Adverse effects include pain at the site of injection, erythema, serum sickness and rarely anaphylactic shock and thrombocytopenia. 

The membrane cast from chloroform-formic acid mixtures had an anisotropic structure with a 0.9-1.2 p active layer and a 40 p porous support layer. At a water flux of 139 1/m2 day (kg/cm2 at 20 °C), the membrane showed 99.4 % rejection of cytochrome C and 72.7% of Vitamine B12. At 3980 1/m2 day water flux level, the rejection for bovine serum hemoglobin (MW, 66000 68000), cytochrome C, and Vitamine Bl2 were, 95.6, 79.4, and 39.8%, respectively. 

Muromonoab-CD3 is used for the treatment of acute organ transplant rejection. It is effective in preventing graft rejection after kidney, heart or liver transplantation. Muromonoab-CD3 is effective in patients who after acute cardiac or liver allograft rejection do not respond to steroid therapy. It is administered intravenously and with a dose of 5 mg/day, a general concentration range of 400-1500 ng/ml can be achieved. A serum concentration of 600-1150 ng/ml in renal transplant patients produces desirable immunosuppressive effects. The levels of CD3 expression, their production and antibodies to the drug determine its rate of clearance. In the absence of antibodies to muromonoab-CD3, its half-life is about 18 h. 

After tissue transplantation, the severity and the period of rejection depend on the tissue type, and this process involves the specificity and memory components of the immune response. Avrion Mitchison in the 1950s observed that allograft immunity could be transferred by the components of the cellular immune response, and antibodies present in the serum that were part of the humoral response were not associated with this process. Future studies delineated the role of T lymphocytes in the allograft rejection process, and the role of both CD4+ and CD8+ cells was established. 

IV. Anti-T-cell Immune serum is obtained from animals immunized with human T-lymphocytes. The antibodies bind to and damage T cells and can thus be used to attenuate tissue rejection. 

We have validated this approach in a study of 33 sequential biopsies from four patients, where 2-D analysis detected 13 proteins that were upregulated more than 5-fold in association with acute rejection in all four patients. Subsequently, two of these proteins (aB-crystallin, tropomyosin) were measured by ELISA and found to be present at significantly higher levels in serum samples associated with biopsy-proven acute rejection (Borozdenkova et al., 2004). 

Figure 4.26 Rejection coefficient of bovine serum albumin (BSA) protein as a function of time for untreated titania membrane and two titania membranes treated with 0.1 M phosphoric acid at room temperature for 1 and 14 hours, respectively. (A) without phosphate buffer (B) with 0.01 M Na2HP04/NaH2P04 buffer [Randon el al.. 1995]...

Antibodies to passenger B lymphocytes can pose problems after transplantation. When kidneys from a rhesus-negative cadaveric donor, whose serum contained anti-Rho (D), were transplanted into two rhesus-positive patients, anti-Rho (D) was detected in their serum and on their erythrocytes 3.5 weeks after transplantation (40). One patient had hemolysis. The antibodies persisted for nearly 6 months, despite graft rejection and nephrectomy in one case. These antibodies presumably arose from passenger B lymphocytes in the grafts from the rhesus-immunized donor. 

---