Specific Donor HLA-DR Types Correlate With Altered Susceptibility to Development of Chronic Lung Allograft Dysfunction.

BACKGROUND: The greatest challenge to long-term graft survival is the development of chronic lung allograft dysfunction. Th17 responses to collagen type V (colV) predispose lung transplant patients to the severe obstructive form of chronic lung allograft dysfunction, known as bronchiolitis obliterans syndrome (BOS). In a previous study cohort (n = 54), pretransplant colV responses were increased in recipients expressing HLA-DR15, consistent with the high binding avidity of colV (α1) peptides for HLA-DR15, whereas BOS incidence, which was known to be strongly associated with posttransplant autoimmunity to colV, was higher in patients who themselves lacked HLA-DR15, but whose lung donor expressed it. METHODS: To determine if this DR-restricted effect on BOS incidence could be validated in a larger cohort, we performed a retrospective analysis of outcomes for 351 lung transplant recipients transplanted between 1988 and 2008 at the University of Wisconsin. All subjects were followed until graft loss, death, loss to follow-up, or through 2014, with an average follow-up of 7 years. Comparisons were made between recipients who did or did not develop BOS. Grading of BOS followed the recommendations of the international society for heart and lung transplantation. RESULTS: Donor HLA-DR15 was indeed associated with increased susceptibility to severe BOS in this population. We also discovered that HLA-DR7 expression by the donor or HLA-DR17 expression by the recipient decreased susceptibility. CONCLUSIONS: We show in this retrospective study that specific donor HLA class II types are important in lung transplantation, because they are associated with either protection from or susceptibility to development of severe BOS.

Monocyte programmed death ligand-1 expression is an early marker for predicting infectious complications in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a life-threatening disease that requires early identification of patients at risk of developing infectious complications. Immunosuppression is an initial event that is key to AP pathogenesis. The programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) system is reported to mediate evasion of host immune surveillance in many diseases; however, the relationship between PD-1/PD-L1 expression and these parameters or infectious complications in AP has not been elucidated. This study was conducted to determine whether PD-1 and PD-L1 are upregulated and to reveal the relationship between PD-1/PD-L1 expression and the development of infectious complications in AP. METHODS: Sixty-three patients with AP and 32 sex- and age-matched healthy control subjects were prospectively enrolled. On days 1 and 3 after the onset of AP, we measured PD-1 expression in peripheral CD4+ T cells and PD-L1 and human leukocyte antigen-DR (HLA-DR) expression in CD14+ monocytes using flow cytometry. Plasma interleukin (IL)-10 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with healthy volunteers, the percentages of PD-1-expressing CD4+ lymphocytes and PD-L1-expressing CD14+ monocytes were increased in patients with AP on days 1 and 3 after onset, especially those with infectious complications. Moreover, increased PD-1/PD-L1 expression was associated with increased occurrence of infectious complications, decreased circulating lymphocytes, and increased plasma IL-10 concentration. Multivariate regression analysis indicated that the increased percentage of PD-L1-expressing CD14+ monocytes was an independent risk factor for infectious complications in AP. Area under the ROC curve analysis showed the combination of Acute Physiology and Chronic Health Evaluation II score and PD-L1 and HLA-DR expression in CD14+ monocytes had high accuracy in predicting infectious complications in patients with AP. CONCLUSIONS: The PD-1/PD-L1 system plays an essential role in the early immunosuppression of AP. PD-L1 expression in CD14+ monocytes may be a new marker for predicting risk of infectious complications in patients with AP.

Frequência, características serológicas e moleculares de hepatite B oculta em dadores de sangue do banco de sangue no hospital Central de Maputo / Frequency, serological and molecular characteristics of occult hepatitis B in blood donors from the blood bank at Maputo Central Hospital

A hepatite B oculta é caracterizada pela presença do ácido desoxiribonucleíco (ADN) do VHB no soro, plasma ou tecido hepático em indivíduos com serologia negativa para o antígeno de superfície (HBsAg). Os mecanismos que conduzem à infecção oculta pelo VHB não são claros, embora as mutações virais sejam provavelmente um factor significativo. O objectivo deste estudo foi determinar a frequência, presença de marcadores serológicos e caracteríticas moleculares dos casos com Hepatite B Oculta em dadores de sangue no banco de sangue do Hospital Central de Maputo. Para tal, 1500 dadores de sangue foram recrutados e testados para HBsAg. As amostras HBsAg negativas foram testadas para identificar à presença de ADN do VHB. Amostras com o ADN do VHB detectado foram submetidas ao nested PCR para amplificação das regiões S e P do genoma de VHB, de seguida foram sequenciadas. A frequência de hepatite B oculta foi de 1,2% (17/1436). Os resultados das análises filogenéticas realizadas em 10 dos 17 casos com hepatite B oculta revelaram que 9 isolados pertenciam ao genótipo A e um isolado pertencia ao genótipo E. Foi encontrada um mutação de escape em uma das amostras e varias substituições de aminoácidos na região S e P. O marcador Anti-HBc foi encontrado na maior parte casos com Hepatite B oculta 76,4% (13/17) e não foi registada a reactividade para HBeAg. Os dados mostram uma urgência de introdução de testes complementares para a exclusão de Hepatite B Oculta e necessidade de maior entendimento dos factores relacionados com a não expressão de HBsAg (Hepatite Oculta).

Occult hepatitis B is characterized by the presence of HBV DNA in serum, plasma or hepatic tissue in subjects with negative serology for the surface antigen (HBsAg). The mechanisms leading to occult HBV infection are unclear, although viral mutations are likely a significant factor. The aim of this study was to determine the presence of HBV serological markers other than HBsAg (anti-HBc, anti-HBs and HBeAg), frequence of OBI and to characterize viral genotypes and mutations among blood donors at the Hospital Central de Maputo. A total of 1500 blood donors were recruited and tested for HBsAg. Serum samples HBsAg negative were tested for presence of HBV DNA. Serum samples HBV DNA detected were submitted to nested PCR for amplifications of S and P regions in HBV genome and sequencing. The frequency of hepatitis B was 4.3% (64/1500) and the frequency of occult hepatitis B was 1.2% (17/1436). The results of the phylogenetic analysis in 10 of 17 cases of occult hepatitis B sequences obtained in this study revealed that 9 isolates belonged to genotype A and only one isolate belonged to genotype E. An escape mutation was found in one of the samples and several amino acid substitutions in the S and P regions in HBV genoma. Anti-HBc marker was found in most OBI cases (76.4%) and no sample was reactive for HBeAg. The data show an urgency to introduce complementary tests for the exclusion of Occult Hepatitis B and need for a better understanding the factors related to non-expression of HBsAg (Occult Hepatitis B).