RESUMEN
Inconsistencies in cardiac rejection grading systems corroborate the concept that the evaluation of inflammatory intensity and myocyte damage seems to be subjective. We studied in 36 patients the potential role of the immunohistochemical (IHC) counting of inflammatory cells in endomyocardial biopsy (EMB) as an objective tool, testing the hypothesis of correlation between the International Society for Heart and Lung Transplantation 2004 rejection and IHC counting of inflammatory cells. We observed a progressive increment in CD68+ cells/mm(2) (P = .000) and CD3+ cells/mm(2) (P = .000) with higher rejection grade. A strong correlation between the grade of cellular rejection and both CD68+ cells/mm(2) and CD3+ cells/mm(2) was obtained (P = .000). One patient with CD3+ and CD68+ cells/mm(2) above the upper limit of the 95% confidence interval for cells/mm(2) found in rejection grade 1R evolved to rejection grade 2R without treatment. In patients with 2R that did not respond to treatment the values of CD68+ or CD3+ cells were higher than the overall median values for rejection grade 2R. For diagnosis of rejection needing treatment, the CD68+ and CD3+ cells/mm(2) areas under the receiver operating characteristic curves were 0.956 and 0.934, respectively. IHC counting of mononuclear inflammatory infiltrate in EMB seems to have additive potential role in evaluation of EMB for the diagnosis and prognosis of rejection episodes.
Asunto(s)
Antígenos CD/inmunología , Rechazo de Injerto/diagnóstico , Trasplante de Corazón , Leucocitos Mononucleares/inmunología , Miocardio/patología , Adulto , Animales , Biopsia , Gatos , Femenino , Rechazo de Injerto/metabolismo , Rechazo de Injerto/patología , Humanos , Inmunohistoquímica , MasculinoRESUMEN
The pathogenesis of rheumatic fever (RF) is related to autoimmune humoral and cellular responses against human tissues triggered by Streptococcus pyogenes. CD4(+) T cells are the ultimate effectors of chronic heart lesions in rheumatic heart disease (RHD). Heart-infiltrating CD4(+) T cell clones are able to recognize heart tissue and streptococcal antigens by molecular mimicry. The streptococcal M5(81-103) region, an immunodominant region, was recognized by both intralesional and peripheral T cell clones (62% and 38%, respectively). Peripheral T lymphocytes from Brazilian patients with severe RHD preferentially recognized the M5(81-96) peptide, in the context of HLA-DR7(+) and DR53(+) molecules. HLA-DR7 seems to be related to the development of multiple valvular lesions in RHD patients from different countries. In addition, the fact that peripheral and intralesional T cells recognized the M5(81-103) region points to this region as one of the streptococcal triggers of autoimmune reactions in RHD. T cell repertoire analysis from peripheral and intralesional T cell lines derived from RHD patients showed several oligoclonal expansions of BV families. Major expansions were found in the heart lesions, suggesting that such T cell populations preferentially migrate from the periphery to the heart. Some cross-reactive intralesional T cell clones displayed the same T cell receptor (TCR) BVBJ and CDR3 sequences, showing a degenerate pattern of antigen recognition. Heart tissue-infiltrating cells from myocardium and valvular tissue produced TNF-alpha, IFN-gamma, IL-10, and IL-4, whereas few cells from valvular tissue produced IL-4, showing that the lack of regulation in the valves could be responsible for the permanent and progressive valvular lesions.
Asunto(s)
Fiebre Reumática/etiología , Cardiopatía Reumática/etiología , Streptococcus pyogenes/inmunología , Linfocitos T/inmunología , Antígenos Bacterianos/fisiología , Autoinmunidad , Proteínas de la Membrana Bacteriana Externa/fisiología , Proteínas Portadoras/fisiología , Citocinas/biosíntesis , Humanos , Fiebre Reumática/inmunología , Cardiopatía Reumática/inmunologíaRESUMEN
OBJECTIVE: To study the diagnostic contribution of repeated transthoracic (TTE) and transoesophageal echocardiography (TOE) among patients with suspected infective endocarditis. METHODS: 262 patients with 266 episodes of suspected infective endocarditis were referred for TTE and TOE over three years in a 423 bed university cardiology hospital. Patients were a mean (SD) of 47.6 (17.9) years old. 139 (52.3%) episodes occurred in men and 127 (47.7%) in women. The diagnostic information obtained from repeated TTE and TOE examinations was evaluated relative to the diagnosis of endocarditis. RESULTS: TTE examinations were repeated in 192 (72.2%) and TOE examinations were repeated in 49 (18.4%) of 266 episodes. A mean of 2.4 TTE and 1.2 TOE examinations were performed for each episode of suspected endocarditis. The second and third TTEs added diagnostic information in 34 (26.7%) and the second and third TOEs added diagnostic information in 25 (19.7%) of 127 episodes with definite endocarditis. After the third TTE or TOE no additional diagnostic information was obtained. CONCLUSIONS: The diagnostic contribution of repeated TTE or TOE for the diagnosis of endocarditis decreased as the number of repetitions increased. In this setting, the data do not substantiate more than three TTE or TOE examinations as an efficient strategy to increase the diagnostic yield for all but selected patients with suspected endocarditis.