Identification and classification of acute cardiac rejection by intragraft transcriptional profiling.

Background-: Treatment of acute rejection (AR) in heart transplantation relies on histopathological grading of endomyocardial biopsies according to International Society for Heart and Lung Transplantation guidelines. Intragraft gene expression profiling may be a way to complement histological evaluation. Methods and results-: Transcriptional profiling was performed on 26 endomyocardial biopsies, and expression patterns were compared with the 1990 International Society for Heart and Lung Transplantation AR grades. Importantly, transcriptional profiles from settings with an equivalent AR grade appeared the same. In addition, grade 0 profiles could not be distinguished from 1A profiles, and grade 3A profiles could not be distinguished from 3B profiles. Comparing the AR groupings (0+1A, 1B, and 3A+3B), 0+1A showed more striking differences from 1B than from 3A+3B. When these findings were extrapolated to the 2005 revised guidelines, the combination of 1A and 1B into a single category (1R) appears to have brought together endomyocardial biopsies with different underlying processes that are not evident from histological evaluation. Grade 1B was associated with upregulated immune response genes, as 1 categorical distinction from grade 1A. Although grade 1B was distinct from the clinically relevant AR grades 3A and 3B, all of these grades shared a small number of overlapping pathways consistent with common physiological underpinnings. CONCLUSION-: The gene expression similarities and differences identified here in different AR settings have the potential to revise the clinical perspective on acute graft rejection, pending the results of larger studie

Cytomegalovirus in colorectal cancer and idiopathic ulcerative colitis Citomegalovírus em câncer coloretal e colite idiopática ulcerativa

Cytomegalovirus (CMV) is a genus in the family Herpesviridae that has been associated with gastrointestinal syndromes. In this work we looked for a possible association of CMV infection with colorectal cancer and ulcerative colitis (UC). Blood and enteric tissue samples of 14 patients with colorectal cancer and of 21 with UC were subjected to a nested-PCR that amplifies part of the gB gene of CMV and also to immunohistochemistry using a specific monoclonal antibody to IE 76kDa protein of CMV. CMV was detected by nested-PCR in the blood and/or the enteric tissue of nine (64.3%) colorectal cancer and 16 (76.2%) ulcerative colitis patients. In the immunohistochemistry it was observed that 12 (12/21, 57.1%) positive enteric tissue samples of patients with UC and none from patients with colorectal cancer (0/14) were positive to CMV. The positivity of CMV infections in the UC patient group (12/21, 57.1%) showed by both techniques, was significantly higher (p = 0.015) than that observed for colorectal cancer patients (2/14, 14.3%). These results suggest an association of ulcerative colitis with CMV infection of the enteric tissue.<br>Os Cytomegalovírus (CMV) são um gênero da família Herpesviridae, que pode estar associado a síndromes gastrointestinais. No presente trabalho buscamos uma possível associação da infecção por CMV com câncer coloretal e retocolite ulcerativa (RCU). Amostras de sangue e tecido entérico de 14 pacientes com câncer coloretal e 21 com RCU foram submetidas a uma nested-PCR que amplifica parte do gene gB do CMV e a uma imunohistoquímica utilizando um anticorpo monoclonal específico para proteína IE 76Kda de CMV. CMV foi detectado pela nested-PCR em sangue e/ou tecido entérico de 9 (64,3%) dos pacientes com câncer coloretal e 16 (76,2%) dos pacientes com RCU. Na imunohistoquímica foram observadas 12 (57,1%) amostras positivas para CMV nos pacientes com RCU e nos pacientes com câncer coloretal o CMV não foi detectado em nenhuma amostra. A positividade das infecções no grupo de pacientes com RCU (12/21, 57.1%) foi significantemente mais alta (p = 0,015) que aquela observada nos pacientes com câncer coloretal (2/14, 14.3%). Estes resultados sugerem uma associação da presença de CMV no tecido entérico com RCU