Algorithms for the determination of unacceptable HLA antigen mismatches in kidney transplant recipients.

One of the major tasks of human leukocyte antigen (HLA) laboratories is the pretransplant determination of unacceptable HLA antigen mismatches (UAM) in organ transplant recipients. HLA antigen specificities are determined against which the patient has circulating alloantibodies that are expected to harm the transplanted organ. Using the information on UAM, negative crossmatch (XM) prediction or 'virtual XM' is possible when a potential donor's complete HLA typing is available. Before the introduction of solid-phase antibody detection assays, UAM were determined using the complement-dependent cytotoxicity methodology. After the introduction of the single antigen bead technique, however, various UAM determination algorithms have emerged. In this report, six different laboratories worldwide present how they determine UAM in their collective of kidney transplant recipients in the pretransplant phase and proceed thereafter to transplantation.

Avaliação da incidência e fatores de risco da retenção de placenta em vacas mestiças leiteiras / Evaluation of incidence rate and risk factors of retained placenta of crossbred dairy cattle

Avaliaram-se a incidência, os fatores de risco e o impacto da retenção de placenta tanto no desempenho reprodutivo quanto no produtivo de vacas mestiças leiteiras, considerando-se: ano e época de parição, ordem de lactação, escore de condição corporal (ECC), duração da gestação, tipo de parto e número e sexo dos bezerros. Utilizaram-se primíparas e multíparas, com e sem retenção de placenta, na época de chuva e de seca, para estudar: período de serviço, número de doses de sêmen/concepção e produção de leite em até 305 dias e no pico da lactação. A incidência da retenção foi de 12,8 por cento. Os fatores de risco da retenção de placenta foram: período de chuvas, ordem de lactação - segunda, terceira e acima da quarta -, ECC abaixo de 3,5 e acima de 4,0 - aborto, natimorto, prematuro, parto auxiliado e parto gemelar. Verificou-se aumento de 51,2 e 27,5 dias no período de serviço e aumento de 1,2 e 0,6 no número de doses de sêmen, em multíparas com retenção de placenta que pariram no período de chuva ou seca, respectivamente (P<0,05).

The incidence rate, risk factors and impact of retained placenta on the reproductive and productive performance of crossbred dairy cows was evaluated. The frequency distribution of retained placenta and also a Poisson multivariate analysis were developed for the following variables: year, calving season, lactation order, body condition score, gestation length, type of delivery, number and sex of calves. First calf heifers and multiparous cows, with and without retained placenta, during the rainy and dry season, had their average results compared in the following items: days from calving to first service, number of semen doses per conception, milk production up to 305 days and lactation peak. The incidence rate of retained placenta was 12.8 percent. The risk factors were: rainy calving season, 2nd, 3rd and above 4th lactation orders, body scores below 3.5 and greater than 4.0, abortion, stillbirth, premature birth, assisted birth and multiple birth. An increase of 51.2 and 27.5 days in the average interval between calving and first service, and of 1.2 and 0.6 in the average number of semen doses was observed in multiparous cows with retained placenta, giving birth during the rainy and dry seasons, respectively (P<0.05).

HLA class II alleles and chronic hepatitis C virus infection.

The aim of this study was to investigate association of human leucocyte antigens (HLA)-DRB1 and DQB1 polymorphisms with hepatitis C virus (HCV) infection and with the occurrence of severe liver fibrosis/cirrhosis in chronically infected patients. Ninety-nine white patients, from southeast Brazil, with confirmed HCV chronic infection were included in the study. Severe fibrosis/cirrhosis (METAVIR scores F3-F4) was present in 49 patients. HLA-DRB1 specificities and DRB1*11 and DQB1* alleles were determined by PCR-SSP, and their frequencies were compared between patients and a control group of 103 healthy white Brazilian individuals. The results confirmed previous reports of the association of DRB1*11 and DQB1*03 with protection from chronic HCV infection, but did not confirm their association with protection from severe fibrosis/cirrhosis. Furthermore, the results suggested that the polymorphic sites on HLA molecules responsible for protection from chronic HCV infection are encoded not only by the DRB1*1101 and DQB1*0301, as suggested in the literature, but also by other DRB1*11 and DQB1*03 alleles. Thus, we hypothesized that the common polymorphic residues shared by different DRB1*11 and/or DQB1*03 alleles might be responsible for selection of viral epitopes for presentation to CD4(+) T cells, leading to an efficient immune response against the virus.

Post-transplant anti-HLA class II antibodies as risk factor for late kidney allograft failure.

The purpose of this study was to prospectively analyze the relationship between the post-transplant anti-HLA class I and/or class II panel reactive antibodies and graft failure due to chronic allograft nephropathy (CAN). We studied 512 first kidney recipients transplanted at a single center, with a graft functioning for at least 3 years. A single blood sample was collected from each patient for antibody evaluation. The median posttransplant time after blood collection was 4.4 years and did not differ between patients with (n = 91) or without anti-HLA antibodies (n = 421). Female gender, pregnancies and blood transfusions were associated with the presence of anti-HLA class I antibodies. Graft function deterioration was associated with anti-HLA class II antibodies. Multivariate analysis showed independent association for creatinine levels (RR = 7.5), acute rejection (RR = 2.6), recipient male gender (RR = 3.6) and anti-HLA class II antibodies (RR = 2.9) and CAN-associated graft loss. In conclusion, the presence of anti-HLA class II antibodies conferred a risk for graft loss before a decline in renal function and increased the risk of graft failure in patients who already had a decline in graft function. Thus, anti-HLA class II antibody monitoring is a useful tool for the management of long-term kidney recipients.