Marita Chakhtoura

The impact of prophylactic antiviral agents and statin administration on graft longevity in kidney allograft recipients

Context: In an earlier study, we compared the duration of kidney graft survival between two groups of recipients; one on triple (cyclosporine, prednisone and mycophenolate mofetil) and the other on quadruple (cyclosporine, prednisone, mycophenolate mofetil, and sirolimus) immunosuppressive therapy. Objective: The aim of this study was to examine the impact of antiviral and statin therapy on graft longevity. Materials and methods: One hundred five kidney allograft recipients were preoperatively assessed for serological markers of infection with various viral agents. All patients were on a prophylactic antiviral regimen of acyclovir and gancyclovir. Seventeen patients were on a statin. Patients were monitored for viral infections and graft rejection or loss for period of 3 years posttransplantation. Results: We detected a high preoperative prevalence rate of IgG immunoglobulins versus the latency-establishing Herpesviridae viruses. Two patients who were preoperatively IgG positive for CMV had cytomegalovirus disease after transplantation. One patient who was preoperatively IgG positive for VZV had shingles after the surgery. No other confirmed viral infections were reported. Thirteen of 88 patients (14.77%) whose treatment regimen did not include a statin suffered a rejection episode or lost the graft whereas 1 of 17 patients (5.88%) on a statin had a rejection episode. Conclusions: The low rate of viral infections observed in our study population supports the utility of prophylactic administration of antiviral agents to transplant recipients. However, statins seem to have a protective effect on graft longevity (odds ratio [OR] = 0.361, 95% confidence interval [CI] = 0.044–2.957).

Advantages of Sirolimus in a Calcineurin-Inhibitor Minimization Protocol for the Immunosuppressive Management of Kidney Allograft Recipients

A myriad of immunosuppressive agents is currently available for the management of graft recipients; however, a consensus on the optimum immunopharmacological plan is nonextant. Twenty kidney recipients on quadruple (mycophenolate mofetil, prednisone, cyclosporine A or tacrolimus, and sirolimus) therapy and 85 on triple therapy where sirolimus was excluded were analyzed for graft rejection or loss within a posttransplant surveillance period of 3 years. Only 1 of 20 recipients (5%) on quadruple therapy experienced a rejection episode. On the other hand, 13 of 85 recipients (15.3%) on triple therapy had a rejection episode or lost the graft. Overall, 14 of 105 recipients (13.3%) experienced a rejection episode or kidney loss. Our observations indicate that an immunosuppressive regimen including sirolimus is advantageous for the management of kidney allograft recipients in the short term.

Influence of HLA disparity, immunosuppressive regimen used, and type of kidney allograft on production of anti-HLA class-I antibodies after transplant and occurrence of rejection

We studied the effects of HLA disparity, immunosuppressive regimen used, and the type of kidney allograft on production of anti-HLA antibodies after transplant and the occurrence of rejection episodes. Five living-unrelated donors and 4 living-related donors kidney recipients received quadruple therapy (including sirolimus and mycophenolate mofetil). Fifteen living-unrelated donors and 19 living-related donors received triple therapy (excluding sirolimus). A single bolus of 4 to 6 mg/kg rabbit anti-human T-lymphocyte immune serum was included with both regimens. Recipients were studied over a 3-year period. Human leukocyte antigen profiles were determined by DNA (SSP) typing, and anti-HLA class-I antibodies were determined by the complement-dependent microcytotoxicity assay and an enzyme-linked immunosorbent assay. The degree of HLA disparity did not appear to affect anti-HLA antibody production or the occurrences of rejection episodes. None of the patients who received quadruple therapy developed anti-HLA class-I antibodies. Two living-unrelated donors and 2 living-related donors recipients who received triple therapy developed anti-HLA class-I antibodies. One of the 2 living-unrelated donors antibody-positive patients rejected the kidney and returned to dialysis, and the other patient has normal graft function 3 years after the transplant. The 2 living-related donors patients with normal graft function were antibody-positive 1 year after the transplant but were antibody-negative at 2 and 3 years after transplant. Sirolimus appeared to inhibit production of antibodies after transplant. Moreover, use of present day immunosuppressive agents diminishes the role of HLA matching in relation to the occurrence of rejection episodes.

Monoclonal antibodies used as prophylactic, therapeutic and diagnostic agents

Monoclonal antibodies can be of mouse, part mouse part human (chimeric, humanized), or of human origin. Their preparation involves hybridoma, gene cloning, gene recombination, phage display, and gene transfection techniques. The preparation, mechanism of action, uses, and possible adverse effects of most of the available monoclonal antibodies used as prophylactic, therapeutic, and diagnostic agents are reviewed.

Alterations In Immunity After Total vs Partial Tonsillectomy

Problem Palatine tonsils are secondary lymphoid organs active in sampling antigens entering the upper respiratory tract and in producing immunoglobulin (Ig) both locally and distally through migrating tonsillar B cells. Their size has been found to be directly proportional to the number of B and T cells. The aim of this study is to compare the change in serum and saliva Ig levels after total and partial tonsillectomy. Methods Children with obstructive tonsils and/or adenoid undergoing total or partial tonsillectomy were recruited in a pilot study. Patients with history of recurrent infections or immunodeficiency were excluded. Blood and saliva samples were obtained immediately preoperatively and at the 1st follow-up visit. Serum Igs (G,M&A) concentrations were determined using radial immunodiffusion. Saliva secretory IgA was measured using an Enzyme Immuoassay (EIA). Results Twenty five patients (13 partial and 12 total) were included. There were no statistically significant changes in serum Igs levels after total or partial tonsillectomy, except for IgM which increased (1.317 to 1.632 g/L) after partial tonsillectomy, more significantly in males, in those aged 5 years and older, and when the postoperative samples were taken within a 2 month-period. Moreover, there was statistically non-significant decrease in secretory IgA level after both total and partial tonsillectomy. Conclusion The effect of partial or total tonsillectomy on immunoglobulin level seems reassuring. The increase in IgM and the non-significant decrease in SIgA may represent a kind of immunological readjustment after tonsillar surgery. Significance This is the first study (to our knowledge) that compares the changes in immunoglobulin levels (in serum & saliva) after partial vs. total tonsillectomy. The obtained results are preliminary and are reassuring to the parents and physicians who have concerns regarding the immunological sequalae of tonsillectomy in children. A longer follow up will be done in a larger future study. Support This study was supported by Medtronic.

Human leukocyte antigen (HLA) associations, antibody titers and circulating immune complexes in patients with cystic echinococcosis

Cystic echinococcosis (CE), caused by the parasite Echinococcus granulosus, is a prominent disease in Lebanon. The objectives of this study were to determine HLA allele-CE association in patients, and relate its presence to high anti-Echinococcus antibody titers and the presence of circulating immune complexes (CIC). Thirty patients and 20 controls were included. HLA profiles were determined by DNA-SSP typing. Relative risk and P-values were determined for each allele using Statcalc (EpiInfo, Version 6). Linkage disequilibrium was determined for associated alleles using SPSS 12.0 for Windows. Antibody titers were determined by indirect hemagglutination (IHA) and CIC by polyethylene glycol (PEG) precipitation. HLA-B*14 and HLA-DRB1*01 appeared to associate with protection against CE (P1 = P2 = 0.007 and P1 = P2 = 0.0007, respectively). However, it appeared that linkage disequilibrium did not exist between these 2 alleles (P = 0.250). HLA-B*35 was found to associate with susceptibility to disease (RR = 1.70, P = 0.02). Twenty five patients had anti-Echinococcus antibodies and 9 patients had CICs. However, there did not appear to be a correlation between the presence of HLA-B*35 and high antibody titers, or the presence of CICs. In conclusion, 2 HLA alleles that associate with resistance and 1 that associates with susceptibility to E. granulosus infection have been identified. The joint pain reported by some of the patients might be attributed to CIC deposits.