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Introdução: O transplante (TX) renal é o tratamento de escolha para insuficiência renal crônica (IRC) terminal. Porém, a rejeição do enxerto pode ocorrer por rejeição humoral. Objetivo: Relatar o caso de um paciente que desenvolveu anticorpo DQ no Pós-TX. Relato de caso: Homem, 37 anos, com IRC terminal, inscrito na Central de TX para realizar TX com rim de doador falecido. Realizou TX em março/2021, com doador mulher, 20 anos. As tipagens HLA (Human Leukocyte Antigen) do receptor e da doadora (A*01:01, A*03:01, B*35:01, B*50:01, DRB1*01:01, DRB1*07:01, DQB1*02:02 e DQB1*05:01) foram realizadas por PCR-SSP®. O par receptor/doador apresentou somente duas identidades HLA. As duas provas cruzadas (PCs) Pré-TX (sorológica e virtual) foram negativas. A PC virtual foi realizada utilizando o Programa de algoritmo EpViX®. A pesquisa de anticorpos de classe I (A* e B*) e II (DR* e DQ*) foi realizada, mas não foi detectado anticorpos no soro Pré-TX fev/2021) e no 3º mês Pós-TX. Porém, o anticorpo anti-DQB1*05:01 foi detectado no 8º mês Pós-TX. A análise da incompatibilidade HLA DQ mostrou que o doador tinha o antígeno DQB1*05:01 ausente no receptor. Discussão: A identificação de anticorpos no Pré-TX caracteriza a sensibilização imunológica prévia do receptor contra antígenos HLA, que podem ocorrer após transplante prévio, transfusões e/ou gestações. Sabe-se que receptores sensibilizados no Pré-TX têm risco aumentado de desenvolver rejeição mediada por anticorpos no Pós-TX, caso os anticorpos sejam dirigidos contra os antígenos HLA do doador. O receptor, do presente caso não tinha anticorpos no Pré-TX e nem no 3º mês do Pós-TX. Porém, foi evidenciado, no 8º mês Pós-TX, a presença do anticorpo anti-DQB1*05:01 de novo, caracterizando a sensibilização do receptor no Pós-TX, com produção de anticorpos contra o antígeno DQB1*05:01 do doador. Estudos têm mostrado que a produção de anticorpos anti-DQ de novo no Pós-TX é a principal causa de rejeição humoral envolvida na perda do enxerto. Conclusão: O monitoramento da sensibilização HLA no Pós-TX é de suma importância para se detectar a produção de anticorpos de novo. Estudos são necessários para se avaliar se o anticorpo DQ de novo detectado causou a rejeição humoral do rim transplantado.

The aim of the study was to evaluate whether the homozygosity of the HLA System alleles presented by transplant recipients in Ceará influenced the waiting time for kidney transplantation. This is a cross-sectional study, carried out based on the active search for medical records, of patients who transplanted with a kidney from a deceased donor in the state of Ceará, from January 2018 to December 2019. Data analysis was performed with 406 patients, 84 were excluded. The mean age and waiting time of 47 ± 13.1 years and 14.64 ± 16.18 months, respectively, were observed. Most patients were male (62.3%) with a mean age greater than women (p=0.0034). The average waiting time was higher in the group of patients who were between 36 and 45 years old (p=0.002) when compared to the other age groups, while the waiting time was higher in group O and group A (p=0.001). There was no influence of homozygosity (p=0.934), number of homozygosis (p=0.448) and presence of homozygosis in different HLA loci (locus A, p=0.169, locus B, p=0.629 and locus DR, p=0.064) on the waiting time. Thus, homozygosity in the different alleles of the HLA system did not influence the waiting time on the list of patients who transplanted in 2018 and 2019. Studies are necessary to better assess the influence of HLA homozygosity in a larger number of receptors, especially in the DR locus. These results will be important to review the selection criteria for potential kidney receptors, since homozygosis is currently not scored. El objetivo del estudio fue evaluar si la homocigosidad de los alelos del sistema HLA influenció en el tiempo de espera para el trasplante renal en Ceará. Se trata de un estudio transversal realizado a partir de la búsqueda activa de historias clínicas de pacientes trasplantados con riñón de donante fallecido en el estado de Ceará, entre enero de 2018 y diciembre de 2019. El análisis de datos se realizó con 406 pacientes, 84 fueron excluidos. La edad media y el tiempo de espera fueron 47 ± 13,1 años y 14,64 ± 16,18 meses, respectivamente. La mayoría eran hombres (62,3%) con una edad media superior a la de las mujeres (p = 0,0034). El tiempo medio de espera fue mayor en el grupo de pacientes entre 36 y 45 años (p = 0,002) y en los del grupo O y el grupo A (p=0,001). No hubo influencia de la homocigosis (p=0,934), del número de hemocigosis (p=0,448) y de la presencia de homocigosis en los diferentes loci HLA (locus A, p=0,169, locus B, p=0,629 y locus DR, p=0,064) sobre el tiempo de espera. La homocigosidad de los alelos del sistema HLA no influenció en el tiempo de espera en la lista de trasplante de riñón en Ceará para los pacientes trasplantados durante el período evaluado, incluso en pacientes con PRA elevado. Se necesitan estudios para evaluar la influencia de la homocigosis en un mayor número de receptores, especialmente en el locus DR. Estos resultados serán importantes para se revisar los criterios de selección de los posibles receptores renales, ya que actualmente no se puntúa la homocigosidad. O objetivo do estudo foi avaliar se a homozigose dos alelos do Sistema HLA influenciou o tempo de espera para realização do transplante renal no Ceará. Trata-se de um estudo transversal realizado a partir da busca ativa de prontuários de pacientes que transplantaram com rim de doador falecido no estado do Ceará, entre janeiro de 2018 a dezembro de 2019. A análise dos dados foi realizada com 406 pacientes, 84 foram excluídos. A média de idade e o tempo de espera foram de 47 ± 13,1 anos e 14,64 ± 16,18 meses, respectivamente. A maioria era do sexo masculino (62,3%) com média de idade superior à do sexo feminino (p=0,0034). A média do tempo de espera foi maior no grupo de pacientes que tinha entre 36 e 45 anos (p=0,002) e naqueles do grupo O e grupo A (p=0,001). Não foi observada influência da homozigose (p=0,934), do número de homozigoses (p=0,448) e da presença de homozigoses nos diferentes loci HLA (locus A, p=0,169, locus B, p=0,629 e locus DR, p=0,064) sobre o tempo de espera. A homozigose dos alelos do sistema HLA não influenciou no tempo de espera na lista para transplante renal no Ceará no período avaliado, mesmo em pacientes com PRA elevado. Estudos são necessários para melhor avaliar a influência da homozigose HLA em um número maior de receptores, em especial no locus DR. Esses resultados serão importantes para se rever os critérios de seleção dos potenciais receptores de rim, uma vez que atualmente a homozigose não é pontuada.

O objetivo do estudo foi avaliar se a homozigose dos alelos do Sistema HLA influenciou o tempo de espera para realização do transplante renal no Ceará. Trata-se de um estudo transversal realizado a partir da busca ativa de prontuários de pacientes que transplantaram com rim de doador falecido no estado do Ceará, entre janeiro de 2018 a dezembro de 2019. A análise dos dados foi realizada com 406 pacientes, 84 foram excluídos. A média de idade e o tempo de espera foram de 47 ± 13,1 anos e 14,64 ± 16,18 meses, respectivamente. A maioria era do sexo masculino (62,3%) com média de idade superior à do sexo feminino (p=0,0034). A média do tempo de espera foi maior no grupo de pacientes que tinha entre 36 e 45 anos (p=0,002) e naqueles do grupo O e grupo A (p=0,001). Não foi observada influência da homozigose (p=0,934), do número de homozigoses (p=0,448) e da presença de homozigoses nos diferentes loci HLA (locus A, p=0,169, locus B, p=0,629 e locus DR, p=0,064) sobre o tempo de espera. A homozigose dos alelos do sistema HLA não influenciou no tempo de espera na lista para transplante renal no Ceará no período avaliado, mesmo em pacientes com PRA elevado. Estudos são necessários para melhor avaliar a influência da homozigose HLA em um número maior de receptores, em especial no locus DR. Esses resultados serão importantes para se rever os critérios de seleção dos potenciais receptores de rim, uma vez que atualmente a homozigose não é pontuada.

We evaluated interleukin-10 (IL10) －592 C/A, IL4－589 C/T, interferon gamma (IFNG)＋874 A/T, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)＋49 A/G gene polymorphisms associated with efavirenz hypersensitivity reaction. A total of 63 human immunodeficiency virus-positive patients under treatment at a public hospital were included in the study, of whom 21 presented with efavirenz hypersensitivity. Patients who presented with efavirenz hypersensitivity reaction showed a higher frequency of the IL10 －592A allele than the controls (p＝0.028). The allele A was associated with increased risk of efavirenz hypersensitivity (odds ratio＝2.40). In case of IL4, a significant difference in the frequency of the IL4 －589 (C/T) polymorphism was not observed between patients and controls. A significant inverse correlation was observed when comparing the CTLA4＋49A/G and IL4 －589 C/T polymorphisms (r＝－0.650, p＝0.001); that is, the CTLA4 +49GG genotype, involved with the lowest capacity of inhibition, was inversely correlated IL4－589TT genotype, which induces high production of IL-4. With respect to the CTLA4＋49A/G and IFNG＋874T/A gene polymorphisms, significant differences in allele and genotype frequencies were not observed between the groups. Therefore, our data suggest that polymorphisms in regulatory regions of cytokine genes could modulate an individual's susceptibility to efavirenz hypersensitivity reaction.

The main objective of the work was to evaluate the use of CD38 on T lymphocytes, IFNγ (+874 A/T), and IL-10 (-1082 A/G) polymorphisms in HIV-infected patients under antiretroviral (ARV) therapy. Sixty-one patients were selected at the outpatient clinic for HIV infection at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. The patients were classified into two groups, according to viral load after one year of ARV therapy. In the aviremic group (group I), a reduction of 35.5% of CD38+CD4+ T cells was observed (p = 0.02) and 49.3% of CD38+CD8+ T cells (p = 0.001). In the viremic group (group II), a reduction of 37.2% of CD38+CD4+ T cells (p = 0.067), and 21.4% of CD38+CD8+ T cells (p = 0.60) occurred. No association was found between IL-10 (-1082) polymorphism and the type of response to ARV therapy. Regarding the gene polymorphism on IFNγ (+874 T/A), 73.34% of group I and 33.3% of group II presented the AA genotype. The relative risk of the individuals carrying AA genotype or the A allele and not being able to suppress the viral load level after one year of ARV therapy was 3.44 (1.25-9.45; p = 0.014) or 2.35 (1.05-5.26; p = 0.027), respectively. Our data suggested that an augmented frequency of activated CD38+CD8+ T cells as well as the presence of the A allele of IFNγ polymorphism could contribute to a reduced virological suppression in patients under antiretroviral therapy.

We evaluated interleukin-10 (IL10) －592 C/A, IL4－589 C/T, interferon gamma (IFNG)＋874 A/T, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)＋49 A/G gene polymorphisms associated with efavirenz hypersensitivity reaction. A total of 63 human immunodeficiency virus-positive patients under treatment at a public hospital were included in the study, of whom 21 presented with efavirenz hypersensitivity. Patients who presented with efavirenz hypersensitivity reaction showed a higher frequency of the IL10 －592A allele than the controls (p＝0.028). The allele A was associated with increased risk of efavirenz hypersensitivity (odds ratio＝2.40). In case of IL4, a significant difference in the frequency of the IL4 －589 (C/T) polymorphism was not observed between patients and controls. A significant inverse correlation was observed when comparing the CTLA4＋49A/G and IL4 －589 C/T polymorphisms (r＝－0.650, p＝0.001); that is, the CTLA4 +49GG genotype, involved with the lowest capacity of inhibition, was inversely correlated IL4－589TT genotype, which induces high production of IL-4. With respect to the CTLA4＋49A/G and IFNG＋874T/A gene polymorphisms, significant differences in allele and genotype frequencies were not observed between the groups. Therefore, our data suggest that polymorphisms in regulatory regions of cytokine genes could modulate an individual's susceptibility to efavirenz hypersensitivity reaction.

The aim of the present study was to investigate the association between polymorphism in the interleukin-10 gene promoter at position −1082 in human immunodeficiency virus-infected patients who had presented allergic reaction due to efavirenz. The study included 63 patients treated at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. Twenty-one patients who had presented allergic reaction to efavirenz were compared to 42 patients with no allergic reaction following exposure to this drug. Blood samples were collected for DNA extraction and submitted to the restriction fragment length polymorphism – polymerase chain reaction technique. The −1082AA genotype was significantly more frequent in allergic patients as compared to non-allergic patients (p = 0.019; χ2 = 5.534; OR = 3.625; 95% CI = 1.210–10.860). Likewise the allele IL-10 −1082A was identified significantly more often among efavirenz allergic patients than in the non-allergic group (p = 0.009; χ2 = 6.787; OR = 3.029; 95% CI = 1.290–7.111). These findings suggest that the polymorphism in the interleukin-10 gene promoter −1082G/A can be related to the development of allergic reactions to efavirenz. Keywords: HIV, Drug allergy, Polymorphism, IL-10

Objective: To determine the rates of red blood cell and leukocyte alloimmunization in patients with chronic kidney disease awaiting kidney transplantation. Methods: In this cross-sectional and prospective study, the serum of 393 chronic kidney disease patients on a transplant waiting list in Ceará, Northeastern Brazil were tested for red cell and leukocyte antibodies. In addition, demographic, clinical and laboratory data were collected. Results: The average age in the sample of 393 patients was 34.1 ± 14 years. Slightly more than half (208; 52.9%) were male. The average numbers of transfusions and gestations were 3.1 ± 3.3 and 1.6 ± 6, respectively. One third (33.6%) were alloimmunized: 78% with leukocyte antibodies, 9.1% with red cell antibodies and 12.9% with both. Red cell antibodies were detected in 29 cases (7.4%), 17 of whom were women, who had received more transfusions than the males (p-value < 0.0001). The most frequently detected red cell antibodies belonged to the Rh (24.1%) and Kell (13.8%) blood group systems. Leukocyte antibodies were detected in 30.5% of cases, 83 of whom were women, who had received more transfusions than the males (p-value < 0.0001) and were more reactive to panel reactive antibodies (p-value < 0.0001). The mean alloreactivity to panel reactive antibodies was 47.7 ± 31.2%. Conclusion: Chronic kidney disease patients on the transplant waiting list in Ceará, Brazil, display high rates of red cell (7.4%) and leukocyte (30.5%) alloimmunization. In this sample, alloimmunization was significantly associated with the number of transfusions and gender.