CD49d is a disease progression biomarker and a potential target for immunotherapy in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene. The immune inflammatory response also contributes to disease progression in DMD patients. In a previous study, we demonstrated higher levels of circulating CD49dhi and CD49ehi T cells in DMD patients compared to healthy control. DMD patients are clinically heterogeneous and the functional defect cannot be correlated with genotype. Therefore, it is important to be able to define reliable noninvasive biomarkers to better define the disease progression at the beginning of clinical trials. RESULTS: We studied 75 DMD patients at different stages of their disease and observed that increased percentages of circulating CD4(+)CD49d(hi) and CD8(+)CD49d(hi) T lymphocytes were correlated with both severity and a more rapid progression of the disease. Moreover, T(+)CD49d(+) cells were also found in muscular inflammatory infiltrates. Functionally, T cells from severely affected patients exhibited higher transendothelial and fibronectin-driven migratory responses and increased adhesion to myotubes, when compared to control individuals. These responses could be blocked with an anti-CD49d monoclonal antibody. CONCLUSION: CD49d can be used as a novel biomarker to stratify DMD patients by predicting disease progression for clinical trials. Moreover, anti-CD49d peptides or antibodies can be used as a therapeutic approach to decrease inflammation-mediated tissue damage in DMD.

Differential integrin expression by T lymphocytes: potential role in DMD muscle damage.

The expression and function of integrin-type extracellular matrix receptors, VLA-4 and VLA-5, and laminin receptor VLA-6 on the surface of CD3(+)CD4(+) and CD3(+)CD8(+) defined T cell populations was evaluated in the blood of Duchenne muscular dystrophy (DMD) patients and healthy individuals. Both the number of CD4(+) and CD8(+) T cell subsets expressing VLA-4 or VLA-5 and the fibronectin-driven T cell migration was significantly higher in DMD patients. These data indicate that interactions of VLA-4 and/or VLA-5 with fibronectin may drive T lymphocytes to specific niches within muscle, contributing to tissue damage and fibrosis in DMD patients.

AIDS in childhood: cardiac involvement with and without triple combination antiretroviral therapy.

OBJECTIVE: To describe the prevalence of cardiac abnormalities in the echocardiogram of children with AIDS followed up in a reference service at 18+/-6 months of AIDS confirmed diagnosis. METHODS: A cross-section study with a cohort after 18+/-6 months of AIDS diagnosis. The study included a total of 93 children with a confirmed diagnosis of AIDS with vertical transmission, with no malignancies and who underwent echocardiogram (echo) during cardiologic evaluation. Cardiac abnormalities were assessed in patients who were not treated (G1) and patients who were treated (G2) with combination antiretroviral therapy. RESULTS: When diagnosed with AIDS, the children were on average 3.07 years old and 50.50% were female. The combination regimen with antiretroviral agents was used by 47 patients (G2). Cardiac involvement was present in 40 children (43.00%). The presence of left ventricular dysfunction (G1: 39.10%; G2: 10.60%) and the isolated enlargement of left ventricle (G1: 6.60%; G2: 14.90%) were the most frequent findings. We observed a significant association between the groups without and with combination antiretroviral therapy asregards the presence of left ventricular dysfunction (PR= 3.42; [1.41-8.26]; p = 0.02) and malnutrition (PR = 1.79; [1.00-3.20]; p = 0.04). CONCLUSION: Cardiac involvement was frequent in children with AIDS and left ventricular dysfunction was the most common abnormality on echocardiogram. There was a statistically significant difference between the groups with and without triple combination treatment as regards the presence of left ventricular dysfunction and malnutrition.

AIDS in childhood: cardiac involvement with and without triple combination antiretroviral therapy / AIDS na infância: acometimento cardíaco com e sem a terapia anti-retroviral tríplice combinada

OBJETIVO: Descrever a prevalência de alterações cardíacas ao ecocardiograma em crianças com AIDS acompanhadas em serviço de referência aos 18±6 meses do diagnóstico confirmado de AIDS. MÉTODOS: Estudo transversal, com corte aos 18±6 meses do diagnóstico de AIDS. Incluídas 93 crianças com diagnóstico confirmado de AIDS por transmissão vertical, sem doença maligna, que, na avaliação cardiológica, realizaram ecocardiograma (eco). De forma exploratória avaliaram-se as alterações cardíacas nos pacientes sem uso (G1) e com uso (G2) de terapia combinada anti-retroviral. RESULTADOS: Quando do diagnóstico de AIDS, as crianças tinham em média 3,07 anos e 50,50 por cento eram do sexo feminino. Esquema de terapia combinado com anti-retrovirais foi utilizado por 47 pacientes (G2). O acometimento cardíaco esteve presente em 40 crianças (43,00 por cento). A presença de disfunção ventricular esquerda (G1:39,10 por cento;G2:10,60 por cento) e o aumento isolado de ventrículo esquerdo (G1:6,60 por cento;G2:14,90 por cento) foram os achados mais freqüentes. Observou-se associação significativa entre os grupos sem e com terapia anti-retroviral combinada quanto à presença de disfunção ventricular esquerda (RP=3,42; [1,41-8,26]; p =0,02) e de desnutrição (RP=1,79; [1,00-3,20]; p=0,04). CONCLUSÃO: O acometimento cardíaco foi freqüente nas crianças com AIDS, sendo a disfunção ventricular esquerda a alteração mais observada ao ecocardiograma. Houve diferença estatisticamente significativa entre os grupos com e sem tratamento tríplice combinado quanto à presença de disfunção ventricular esquerda e de desnutrição.

OBJECTIVE: To describe the prevalence of cardiac abnormalities in the echocardiogram of children with AIDS followed up in a reference service at 18±6 months of AIDS confirmed diagnosis. METHODS: A cross-section study with a cohort after 18±6 months of AIDS diagnosis. The study included a total of 93 children with a confirmed diagnosis of AIDS with vertical transmission, with no malignancies and who underwent echocardiogram (echo) during cardiologic evaluation. Cardiac abnormalities were assessed in patients who were not treated (G1) and patients who were treated (G2) with combination antiretroviral therapy. RESULTS: When diagnosed with AIDS, the children were on average 3.07 years old and 50.50 percent were female. The combination regimen with antiretroviral agents was used by 47 patients (G2). Cardiac involvement was present in 40 children (43.00 percent). The presence of left ventricular dysfunction (G1: 39.10 percent; G2: 10.60 percent) and the isolated enlargement of left ventricle (G1: 6.60 percent; G2: 14.90 percent) were the most frequent findings. We observed a significant association between the groups without and with combination antiretroviral therapy asregards the presence of left ventricular dysfunction (PR= 3.42; [1.41-8.26]; p = 0.02) and malnutrition (PR = 1.79; [1.00-3.20]; p = 0.04). CONCLUSION: Cardiac involvement was frequent in children with AIDS and left ventricular dysfunction was the most common abnormality on echocardiogram. There was a statistically significant difference between the groups with and without triple combination treatment as regards the presence of left ventricular dysfunction and malnutrition.