Outcomes of kidney transplantation over a 16-year period in Korea: An analysis of the National Health Information Database.

BACKGROUND: This study investigated the outcomes of kidney transplantation (KT) over a 16-year period in Korea and identified risk factors for graft failure using a nationwide population-based cohort. METHODS: We investigated the Korean National Health Insurance Service-National Health Information Database. Health insurance claims for patients who underwent KT between 2002 and 2017 were analyzed. RESULTS: The data from 18,331 patients who underwent their first KT were reviewed. The percentage of antithymocyte globulin (ATG) induction continuously increased from 2.0% in 2002 to 23.5% in 2017. Rituximab began to be used in 2008 and had increased to 141 patients (9.6%) in 2013. Acute rejection occurred in 17.3% of all patients in 2002 but decreased to 6.3% in 2017. The rejection-free survival rates were 78.8% at 6 months after KT, 76.1% after 1 year, 67.5% after 5 years, 61.7% after 10 years, and 56.7% after 15 years. The graft survival rates remained over 80% until 12 years after KT, and then rapidly decreased to 50.5% at 16 years after KT. In Cox's multivariate analysis, risk factors for graft failure included being male, more recent KT, KT from deceased donor, use of ATG, basiliximab, or rituximab, tacrolimus use as an initial calcineurin inhibitor, acute rejection history, and cytomegalovirus infection. CONCLUSIONS: ATG and rituximab use has gradually increased in Korea and more recent KT is associated with an increased risk of graft failure. Therefore, meticulous preoperative evaluation and postoperative management are necessary in the case of recent KT with high risk of graft failure.

A single-center analysis of early readmission after renal transplantation.

BACKGROUND: Thirty-day readmission rates (early hospital readmission, EHR) are an important benchmark for quality improvement. Nationally, patients undergoing renal transplantation incur a 31% EHR rate. While national databases provide useful data, the impact of EHR on individual centers has received little attention. We proposed that an institutional review of EHR after renal transplantation may provide a benchmark for individual transplant programs and identify modifiable program-specific issues to reduce EHR. METHODS: We reviewed 269 consecutive kidney transplant recipients over a five-year period (2012-2016). Early hospital readmission was modeled using generalized linear modeling assuming a binary distribution. RESULTS: About 21% of patients were readmitted within 30 days. Deceased kidney donation (DD), delayed graft functioning (DGF), anti-thymocyte globulin (ATG) induction, diabetes, public insurance, weekend discharge, and low glomerular filtration rate (eGFR) at discharge were all identified as risk factors for readmission. Early hospital readmission was not correlated with risk of death (5.4% at 44 months: HR 2.2 (95% CI [0.7, 6.6]; P = 0.1473) or graft loss. CONCLUSIONS: EHR after renal transplantation is common. Certain factors may predict an increased risk for EHR. A multi-disciplinary approach to discharge planning may limit some EHR, but most complications and adverse events are unpredictable and require hospital-level of care.

Urinary iodine concentrations of pregnant women in Ukraine.

BACKGROUND: Iodine requirements increase during pregnancy and previous studies have reported the inadequate iodine status of pregnant women in areas that have achieved iodine sufficiency in the general population. We examined the urinary iodine (UI) concentrations of pregnant women in Ukraine, where the iodine status is showing improvement among the general population. METHODS: We enrolled 148 pregnant women<16 weeks pregnant and 80 healthy women as a control group living in Zhitomir, Ukraine. UI concentration, thyroid-stimulating hormone (TSH), antithyroglobulin antibodies (TGAb), and antithyroid peroxidase antibodies (TPOAb) were measured. RESULTS: The median UI concentrations were significantly lower in pregnant women than in control women [13.0 (ND­51.0) µg/L vs. 62.0 (35.3­108.5) µg/L, p<0.001]. TSH concentrations were significantly lower in pregnant women than in control women [1.7 (1.2­2.7) IU/L vs. 2.2 (1.4­3.1) IU/L, p=0.011], but this difference disappeared when adjusted for age (2.1±0.1 IU/L vs. 2.4±0.2 IU/L, p=0.097). The frequency of TSH over 6.2 IU/L and the frequency of positive TGAb and/or TPOAb were not statistically different between groups (p=0.70 and p=0.48, respectively). The UI concentrations of 142 pregnant women (95.9%) were <150 µg/L indicating insufficient iodine intake. CONCLUSIONS: The UI concentration of pregnant women in Ukraine revealed severe iodine deficiency. Regular monitoring and appropriate nutrition education are essential because iodine deficiency can be easily prevented by adequate iodine intake. The risk of iodine deprivation during pregnancy needs to be assessed locally over time because it may occur in areas that are not globally recognized as being iodine-deficient.

A comparison of Jurkat cell-reactive anti-T lymphocyte globulin and fetal anti-thymocyte globulin preparations in the treatment of aplastic anemia.

OBJECTIVE: The aim of this study was to investigate the success rate and effects on survival of different anti-thymocyte globulin (ATG) preparations in patients diagnosed with aplastic anemia. SUBJECTS AND METHODS: Of the total 24 patients included in the study, 12 were male and 12 female with a median age of 44 years (range 16-72). Nine patients received Lymphoglobulin®, 7 Thymoglobulin® and ATG-Fresenius® (ATG-F). There was no significant difference between the three treatment groups in terms of severity of aplastic anemia. RESULTS: The estimated 6-month survival rates for ATG-F, Lymphoglobulin and Thymoglobulin groups were 42.9, 77.8 and 71.4%, respectively. The difference in overall survival rates between groups was not significant, most likely due to the low number of patients. The most striking result was that none of the patients in the ATG-F preparation group showed any response to treatment. The ATG-F group was found to have a significantly inferior response rate (p = 0.07). CONCLUSION: Our data showed that none of the patients responded to ATG-F treatment. Hence, despite the small number of the patients, we recommend that ATG-F should not be used for treatment of severe aplastic anemia.

A novel analytical ELISA-based methodology for pharmacologically active saikosaponins.

A competitive enzyme-linked immunosorbent assay (ELISA) for saikosaponins was established using monoclonal antibody (MAb) 3G10. Hybridoma 3G10 prepared by fusing splenocytes immunized with saikosaponin a-BSA (SSa-BSA) conjugate and a hypoxanthine-aminopterin-thymidine (HAT)-sensitive mouse myeloma cell line, P3-X63-Ag8-U1, secreted monoclonal antibodies with wide cross-reactivity to saikosaponins including saikosaponin b(2) (SSb(2)), c (SSc) and d (SSd), which are stereo and/or regio isomers of SSa. The method, at an effective measuring range of 0.6 mug /ml to 2.3 mug/ml of SSa, successfully detected total saikosaponins in Bupleuri radix and Kampo medicines prescribed with Bupleuri radix. Good correlation between ELISA and HPLC analyses of total saikosaponin in a crude extract of Bupleuri radix was obtained after hydrolysis of acyl saikosaponins by treatment with a mild alkaline solution.

Amotosalen interactions with platelet and plasma components: absence of neoantigen formation after photochemical treatment.

BACKGROUND: The INTERCEPT Blood System (Baxter Healthcare Corp., and Cerus Corp.) is a photochemical treatment (PCT) process that uses amotosalen (S-59) and ultraviolet A (UVA) illumination to inactivate a broad spectrum of pathogens. STUDY DESIGN AND METHODS: To evaluate the potential of the process to create neoantigens, the amounts of residual amotosalen and photoproducts present in PCT platelets (PLTs) and PCT plasma were quantified. The initial amount of amotosalen was 150 micromol per L. After illumination with 3 J per cm2 UVA and before transfusion, a compound adsorption device was used to substantially reduce the amounts of free amotosalen and unreactive photodegradation products. Patient serum samples from Phase III clinical trials were assayed by enzyme-linked immunosorbent assay (ELISA) for antibodies to potential amotosalen neoantigens. RESULTS: After PCT, 15 percent of the starting amount of amotosalen remains bound to PLTs, and 15 to 22 percent remains bound to plasma components. The majority of bound amotosalen is associated with lipid. Less than 1 percent of PLT-bound amotosalen and approximately 2 percent of plasma-bound amotosalen can be extracted into the water-soluble protein fraction. In seven Phase III clinical trials, 523 patients received more than 8000 units of PCT PLTs or PCT plasma. None of the patients exhibited clinical or laboratory manifestations of neoantigenicity. Furthermore, no other alteration of PLT membrane proteins was identified based on testing for lymphocytotoxic antibodies and PLT-specific alloantibodies. CONCLUSION: These results indicate that no neoantigens were detected by ELISA after PCT, suggesting that transfusion of PCT PLTs or PCT plasma does not induce adverse immunologic responses.

A quantitative flow cytometry assay for the preclinical testing and pharmacological monitoring of rabbit antilymphocyte globulins (rATG).

Rabbit antilymphocyte or antithymocyte globulins (rATG) are currently used as immunosuppressive agents in clinical organ and bone marrow transplantation, but because of differences in antigen source and purification processes between manufacturers, determination of the dose to be administered remains empirical. Dosage may be adjusted to peripheral blood T cell counts or limited by side effects such as neutropenia or thrombocytopenia. We report here a measurement by indirect immunofluorescence of the amount of antibodies from rATG that bind to different blood cell types. A concentration-related immunofluorescence signal was obtained with reasonable replicability, allowing comparison of different rATGs by reference to the same rATG batch as internal standard. Ratios of antilymphocyte to undesirable antibodies (directed against antigens expressed on neutrophils, platelets or red cells) could be calculated for each rATG preparation. Finally, the method is applicable to the measurement of free antibodies in sera from patients treated with rATG and to the analysis of the effects of in vivo absorption of rATG during its administration. Marked differences in antibody content per mg of rIgG account for the differences in rATG dosage that were empirically established for clinical applications.

Avaliaçäo de testes imunológicos em pacientes com aborto recorrente / Evaluation of immunologic tests in recurrent abortion

INTRODUÇÃO: O aborto recorrente é um grande enigma, pois apesar de várias causas que lhe säo atribuidas poucas tem um real valor. O papel do fator imunológico tem sido pesquisado amplamente. OBJETIVO: Avaliar alguns testes imunológicos em pacientes com aborto recorrente. TIPO DE ESTUDO: prospectivo LOCAL: Setor de Reproduçäo Humana do Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeiräo Preto. PARTICIPANTES: Num estudo piloto foram selecionados nove casais com duas perdas fetais ou mais sem causa aparente e nove casais voluntários com pelo menos dois filhos, sem história de aborto e com idade inferior a 40 anos VARIAVEIS ESTUDADAS: A freqüência de compartilhamento de antígenos HLA e de anticorpos linfocitotóxicos contra antígenos paternos foram avaliados por métodos sorológicos, a variaçäo de fenótipos celulares (CD4, CD8, CD19, CD16, CD56 e HLA-DR) por citometria de fluxo, a atividade "natural killer" (NK) pela liberaçäo de 51Cr e a dosagem de progesterona por radioimunoensaio. RESULTADOS: Näo houve diferença de compartilhamento entre casais com aborto recorrente tanto em relaçäo à classe I quanto II e näo se detectou o aparecimento de anticorpos citotóxicos no grupo investigado. Houve um número absoluto maior de células CD8+(587 vs 448 linfócitos/mmü, p=0,01) e das CD19+(215 vs 182 linfócitos/mmü, p=0,05) nas pacientes. A atividade NK näo foi estatisticamente diferente entre os dois grupos estudados, mas houve uma tendência à reduçäo da atividade NK entre pacientes com aborto recorrente. Näo houve correlaçäo da atividade NK com um número de células CD16+ e CD56+ nem com dosagem de progesterona nos dois grupos estudados. CONCLUSÃO: Estes dados sugerem que o compartilhamento de antígenos HLA, o aparecimento de anticorpos linfocitotóxicos e elevaçäo da atividade NK podem näo ser importantes para a ocorrência de abortos repetidos. o aumento de células CD8+ e CD19+ circulantes pode ocorrer independente de qualquer terapêutica e a citotoxicidade contra antígenos fetais pode ser mediada por células T e näo por células NK.

Standardized flow cytometry gating in veterinary medicine.

Gating in flow cytometry is used to select subpopulations of cells for analysis. The technique is critical for subsequent analysis in order to select the population, free of debris and unrelated cells. Accurately quantifying subpopulations in clinical cases is necessary for correct diagnosis. Human lymphocytes are selected by backgating on populations of CD45+high CD14- cells. These reagents are not available widely across species. In veterinary medicine, markers to identify lymphocytes are usually limited to T-lymphocyte, CD4, CD8, and B-lymphocyte surface antigens. A standardized gating technique using a T-lymphocyte antibody is described and is applicable across species where limited phenotype markers are available.

Early recipient-donor switch of the complement type after liver xenotransplantation.

Liver transplantation is an immunological peculiarity with respect to the resistance of the graft to humoral rejection. We undertook a kinetic analysis of molecules involved in humoral rejection for a period of one week following xenografting in the hamster to rat model system. A complement-dependent lymphocytotoxicity test (CDC) was used to detect anti-donor antibodies in the recipient rats. Complement was studied by two methods. Function of the classical complement pathway was evaluated with a hemolytic assay, and C3 was measured by radial immunodiffusion. Conversion of the major plasma proteins from recipient to donor profile was studied by zone electrophoresis on agarose. CDC showed antibody titers rose during the first week post-transplantation, and they were of complement-activating isotypes. Zone electrophoresis showed almost complete replacement of rat C3 by hamster C3 within 72 hours. Hemolytic assay of complement on day 6 post-transplant showed serum of the xenograft recipients could lyse erythrocytes sensitized with rat antibody with 80% of efficiency of normal rat serum. Our data show the effector molecules for humoral rejection, rat antibodies with anti-hamster specificity and a functional complement cascade, were present within the first week following transplantation. Rapid conversion of serum complement to hamster proteins maintains compatibility with the species-specific membrane inhibitors of complement activation expressed by the xenografted hepatocytes, and could limit complement-mediated damage.

MHC class II genes influence the susceptibility to chronic active hepatitis C.

BACKGROUND/AIMS: Chronic hepatitis C develops in more than 70% of hepatitis C virus infected subjects. Viral factors influence the disease course, but little is known about the importance of host factors. METHODS: Frequencies of major histocompatibility complex (MHC) class I and class II antigens were analyzed in two groups of patients with chronic hepatitis C virus infection and in control subjects. MHC class I typing was done by standard microlymphocytotoxicity assays. DRB1 and DQA1 genotyping was done by PCR based typing methods. RESULTS: DRB1*0301 was found in 26 of 75 patients with chronic hepatitis C virus infection (34.7%) and in 12 of 101 control subjects (11.9%) (relative risk 3.9; p < 0.001). Homozygosity for this allele appeared to confer a stronger risk. In contrast, DRB1*1301 was detected in three subjects with persistent infection (4.0%) compared to 21 control subjects (20.8%) (relative risk 0.2; p < 0.008). This allele was linked with DQA1*0103, which was found in 10 patients (13.3%) compared to 34 control subjects (33.7%) (relative risk 0.31; p < 0.003). An even stronger protective effect was provided by the presence of DRB1*1301 and DQA1*0103 (relative risk 0.08; p < 0.005). These findings were confirmed in a second group of chronic hepatitis C virus infected patients. CONCLUSIONS: The MHC class II allele DRB1*0301 appears to predispose to progression to chronic active hepatitis C, whereas the class II alleles DRB1*1301 and DQA1*0103 appear to provide protection against chronic active infection with hepatitis C virus.

Anti-ribosomal and 'P-peptide'-specific autoantibodies bind to T lymphocytes.

Patients with systemic lupus erythematosus (SLE) frequently have anti-lymphocyte autoantibodies, some of which also bind to surfaces of neurons. Since anti-ribosomal P protein autoantibodies (anti-P) from SLE patients also bind to surfaces of neurons, we hypothesized that anti-P are anti-lymphocyte antibodies. A panel of human T lymphocytes was evaluated for anti-P binding by indirect immunofluorescence. Affinity-purified anti-ribosomal antibodies were used as a source of anti-P. These autoantibodies bound to the surfaces of all transformed T cell lines tested. This binding was not mediated by Fc receptors. It was inhibitable by ribosomes. Anti-P bound to circulating T lymphocytes from healthy adults and children. They also bound to thymocytes and cord blood T cells from normal neonates. Circulating T cells from SLE patients with anti-P bound less anti-P than cells from healthy controls. Two patients were studied on multiple occasions. The capacity of their T cells to bind anti-P correlated inversely with titres of anti-ribosomal antibodies. Anti-ribosomal antibodies, other than anti-P, also appear to bind to T cells. The surface of T cells contains a protein with the size and antigenicity of the ribosomal P protein, P0. We conclude that anti-ribosomal antibodies are a subset of anti-lymphocyte autoantibodies. Their possible role in the pathogenesis of lymphopenia or lymphocyte dysfunction in SLE has to be defined in further studies.

Is immunogenetic susceptibility to neuropsychiatric systemic lupus erythematosus (SLE) different from non-neuropsychiatric SLE?

OBJECTIVES: To analyse frequency of HLA class II antigens (DR and DQ) and lymphocytotoxic autoantibodies in patients with systemic lupus erythematosus (SLE) and subsets with or without neuropsychiatric involvement. METHODS: Ninety three patients with SLE (42 with neuropsychiatric features) were typed for HLA class II antigens and investigated for the presence of lymphocytotoxic autoantibodies by a complement dependent microlymphocytotoxicity assay. A total of 191 controls of similar ethnic background were also typed for HLA antigens. RESULTS: HLA-DR3 antigen was increased in the total group of patients with SLE (p = 0.003) and in the neuropsychiatric group (p = 0.002). HLA-DR4 antigen frequency was increased in non-neuropsychiatric patients (p = 0.001) and decreased in patients with neuropsychiatric SLE (p = 0.0005). Comparisons of HLA frequencies between subgroups of patients showed decreased HLA-DR4 (p < 0.0001) and increased HLA-DR9 and HLA-DQ2 antigens (p = 0.0008 and 0.005 respectively) in the neuropsychiatric group. The frequency of lymphocytotoxic autoantibodies was increased in neuropsychiatric patients with SLE having HLA-DR9 specificity (p = 0.04). CONCLUSION: HLA-DR4 may have a protective specificity for the development of neuropsychiatric features of SLE and HLA-DR9, in addition to HLA-DR3, and the presence of lymphocytotoxic auto-antibodies may predispose to neuropsychiatric abnormalities.

Experimental hyperacute rejection in pancreas allotransplants.

A model of sensitization by intraperitoneal lymph node inoculation was developed to test the hypothesis that hyperacute rejection (HAR) could occur in sensitized recipients of vascularized pancreas allografts. Ten pairs of outbred mongrel dogs that were lymphocytotoxic cross-match assay negative were inoculated with homogenized lymph nodes on either three or four occasions at fortnightly intervals before renal transplantation. A renal allograft from the same donor was used to test the HAR response and to further enhance sensitization by rejection of a vascularized organ. Pancreas transplants were performed 2 weeks later, with biopsies of the graft and blood samples taken at 0, 10, 20, and 30 min and then at 30-min intervals until the grafts were no longer viable. All renal and pancreas grafts were rejected in a classical hyperacute pattern. Within 4 min of revascularization of the pancreas, central lobular hemorrhage and vascular congestion appeared, followed by general edema. Histology demonstrated parallel changes of edema, vascular congestion, necrosis, hemorrhage, and leukocytic infiltrate, which all preceded graft infarction. A sharp decline in both arterial and venous white blood cell count and platelets occurred within 10 min of revascularization with initial sequestration and subsequent release of platelets from the graft (P=0.02). In summary, HAR of the allografted pancreas can be observed by the surgeon within minutes of revascularization, with predictable macroscopic and microscopic changes. This study supports the use of routine lymphocytotoxic cross-match tests for all recipients of pancreas transplants and implies that particular care is warranted in regraft pancreas allograft recipients.

[Idiopathic habitual abortion: experiences with active immunotherapy]. / Idiopathische habituelle Aborte: Erfahrungen mit der aktiven Immuntherapie.

The effect of lymphocyte transfusions on the stabilisation and successful outcome of pregnancy was investigated in 30 women with recurrent abortions presumably caused by immunologic factors. Lymphocyte concentrates were obtained from stored whole blood of the husbands and transferred by intravenous injection. Exclusion criteria for this study were the presence of antipaternal lymphocytotoxic antibodies in the patient's serum (cross match) or an advanced pregnancy (> 12 weeks). After transfusion of paternal lymphocytes 19 (63%) women had uncomplicated and successful pregnancies whereas 11 (37%) suffered again from early pregnancy loss. Two out of these 11 patients aborted twice. The probability of a successful treatment decreased as soon as lymphocytotoxic antibodies appeared in the patient's serum (p < or = 0.021). Women with a lower number of abortions before treatment carried their pregnancies to full term more frequently (p < or = 0.03). The number of transfusions, the period between start of treatment and conception as well as the distribution of age within the two groups had no significant effect on the outcome of therapy. A lack of lymphocytotoxic antibodies or their late appearance during treatment give a positive prognosis for the progress of pregnancy. Compared with a fertile control group, couples with habitual abortions showed no significantly increased HLA sharing. Immunisation with paternal lymphocytes in cases of presumably habitual abortions due to immunologic factors appears as an effective therapy with only few side effects. Large, randomised, double-blind, and placebo-controlled trials are needed before drawing conclusions.

Pilot study of low-dose azathioprine in presensitized patients awaiting heart or lung transplantation.

In an effort to reduce the level of presensitization in patients on our heart and lung transplant waiting list, ten patients with random panel reactivity above 10% on monthly screening for durations of 2 to 59 months were given low-dose azathioprine (25 to 75 mg/day) for 1 to 22 months. All patients had positive T-cell panel reactivity (10% to 70%) against specific (n = 6), multi-specific (n = 1), or undefined (n = 3) HLA loci, and four additional patients had positive B-cell panel reactivity (5% to 40%). No effect of azathioprine on panel reactivity was seen in four of ten patients (40%), whereas a significant and sustained reduction in panel reactivity occurred in six patients (60%), all within 2 months of commencing azathioprine. All nonresponders had antibodies with class I (A locus) specificity, whereas all six responders had multi-specific or undefined antibody specificities. A formal trial of low-dose azathioprine in presensitized recipients is warranted.

Humoral immune response to human aortic valve homografts.

The humoral response to homograft valves in humans is largely unknown. The anti-human lymphocyte antigen (HLA) antibody production, specificity, and immunoglobulin class were examined sequentially in 73 patients undergoing aortic valve replacement. In addition, the long-term production of antibodies was examined in a cross-sectional study of 160 patients at periods varying from 1 to 15 years postoperatively. Human lymphocyte antigen antibodies were produced in 17 of 30 antibiotic-sterilized homografts (56%) and in 15 of 15 "homovital" homograft recipients, compared with 6 of the 28 control xenograft recipients (21%) (p < 0.001). The HLA antibodies were immunoglobulin G in all 15 homovital homografts, in 11 of 17 antibiotic-sterilized homografts, and in four of the six xenograft cases. Human lymphocyte antigen specificities could be assigned to the antibodies in 21 cases. In 10 of 11 cases in which donor HLA typing data were available, the antibodies detected were directed against donor HLA class I antigens. Of six possible determinants of HLA antibody production, the type of homograft valve implanted (homovital or antibiotic sterilized) correlated with antibody formation. In the cross-sectional study, 66 of the 85 homovital homograft recipients tested for HLA antibodies after 1 year were found to have antibodies, compared with 29 of 75 antibiotic-sterilized homograft recipients (p = 0.00003). We conclude that homografts appear to stimulate a strong donor HLA-specific antibody response, particularly of the immunoglobulin G class. This is most common in homovital valve recipients. These antibodies can persist for 15 years after operation. The clinical significance of this response requires further investigation.

Niveles de anticuerpos anti-Gal en personas infectadas y no-infectadas por trypanosoma cruzi: probable inducción por bacterias y por el parásito / Anti-Gal antibodies levels in trypanosoma cruzi infected and non-infected persons: probable induction by bacteria and by the parasite

Se estudiaron los niveles de anticuerpos contra epítopes Gal Ó 1,3 Gal en 407 sueros humanos chagásicos (92) y no chagásicos (315), mediante la reacción de hemaglutinación con eritrocitos de conejo; con inmunoelectrotransferencia se investigó la reactividad de sueros con altos títulos de anticuerpos anti-Gal frente a antígenos de escherichia coli y serratia marcescens. Finalmente, utilizando un anticuerpo anti-Gal purificado se identificó epítopes Gal Ó 1,3 Gal en formas metacíclicas de 12 cepas altoandinas chilenas de trypanosoma cruzi. Entre los 92 sueros chagásicos, se demostró que en el 68,5 por ciento (63) de los menos chagásicos se detectó anticuerpos anti-Gal a títulos ò 1:1.600, mientras que entre los sueros no chagásicos, sólo el 15,6 por ciento (49) mostró respuesta anti-Gal a títulos similares. Estos datos sugieren que la determinación de estos anticuerpos podría contribuir a complementar el diagnóstico de la infección, especialmente cuando se establezcan títulos de corte ò 1:3.200. La inmunoelectrotransferencia mostró que sueros de personas infectadas con T. cruzi reconocen varios antígenos presentes en E. coli y S. marcescens, lo que refuerza la idea de que a lo menos en parte estas bacterias serían capaces de estimular estas respuestas. El análisis autorradiográfico utilizando anticuerpo anti-Gal purificado, mostró diferencias en la expresión de los epítopes Gal Ó 1,3 Gal en las diferentes cepas de T. cruzi. Estos resultados sugieren que los anticuerpos anti-Gal podrían tener real significado en los mecanismos de inmunidad natural y protección de la infección en chilenos infectados con T. cruzi

Immunoglobulin G lymphocytotoxic antibodies in clinical liver transplantation: studies toward further defining their significance.

Twenty-two consecutive liver allograft recipients, who tested positive for immunoglobulin G (IgG) lymphocytotoxicity were subjected to pretransplantation and posttransplantation immunologic monitoring of anti-donor IgG lymphocytotoxic antibody titers, total hemolytic complement activity (CH100), circulating immune complexes (CIC), and platelet counts in an effort to improve our understanding of the preformed antibody state in clinical hepatic transplantation. Ten contemporaneous liver transplant recipients whose crossmatch results were negative and who experienced severe hepatocellular damage early after transplantation were included as controls. Crossmatch test results were negative 1 day after transplantation and during the 1 month follow-up remained negative in 14 of 22 (64%) sensitized recipients, most of whom had relatively low (< or = 1:16) anti-donor IgG antibody titers before transplantation. After transplantation, this group and the control group experienced no thrombocytopenia, no increase of CIC, and a gradual increase in CH100 activity that reached normal levels within 1 week. A strong negative correlation between prothrombin time (PT) and CH100 activity in these groups of patients suggested that changes in CH100 activity (P < .0005) were tightly linked to liver synthetic function. In contrast, the crossmatch test results remained positive after transplantation in 8 of 22 (36%) sensitized recipients, all of whom had relatively high (> 1:32 to 1024) pretransplantation titers of anti-donor IgG antibodies. After transplantation these patients developed a syndrome that was characterized by decreased CH100 activity and increased CIC compared with pretransplantation levels and refractory thrombocytopenia that was associated with a 50% allograft failure rate because of biopsy-proven humoral and acute (cellular) rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of total blood exchange with PHP solution on cardiac xenotransplantation.

Prevention of hyperacute rejection is a difficult and unsolved problem in xenotransplantation. Natural antibodies and complement activation have been known to play an important role in the xenotransplantation between discordant species pairs. In the present study, total blood exchange (TBE) was performed with pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP) solution (Ajinomoto Co., Inc., Kawasaki, Japan) before cardiac xenotransplantation in order to remove the immunoglobulins and prolong xenograft survival time. Guinea pigs and rats were used as the discordant species combination for donor and recipient. Two groups were established: Group 1, untreated control (n = 8) and Group 2, TBT with PHP solution (n = 8). The exchange blood transfusion was carried out at the rate of 15-20 ml/h utilizing PHP solution using a blood pump. After the blood exchange was processed, hematocrit (Ht) levels dropped to 4 or 5%, and a cardiac xenotransplantation was performed within 24 h. The levels of serum IgA, IgM, and IgG were decreased to less than 25, 25, and 10% of the base line, respectively, after blood exchange. A mean xenograft survival time in Group 2 was prolonged to 472 +/- 74 min and to 10.4 +/- 1.8 min in Group 1 (p < 0.01). A titer of the anti-guinea pig lymphocytotoxic antibody in rat serum was decreased to almost nil. The data from this study suggest that total blood exchange with PHP solution may be useful in preoperative removal of xenograft antibodies in xenotransplantation.