Association between textural and morphological tumor indices on baseline PET-CT and early metabolic response on interim PET-CT in bulky malignant lymphomas.

PURPOSE: We investigated whether metabolic, textural, and morphological tumoral indices evaluated on baseline PET-CT were predictive of early metabolic response on interim PET-CT in a cohort of patients with bulky Hodgkin and non-Hodgkin malignant lymphomas. METHODS: This retrospective study included 57 patients referred for initial PET-CT examination. In-house dedicated software was used to delineate tumor contours using a fixed 30% threshold of SUV max and then to compute tumoral metabolic parameters (SUV max, mean, peak, standard deviation, skewness and kurtosis, metabolic tumoral volume (MTV), total lesion glycolysis, and area under the curve of the cumulative histogram), textural parameters (Moran's and Geary's indices, energy, entropy, contrast, correlation derived from the gray-level co-occurrence matrix, area under the curve of the power spectral density, auto-correlation distance, and granularity), and shape parameters (surface, asphericity, convexity, surfacic extension, and 2D and 3D fractal dimensions). Early metabolic response was assessed on interim PET-CT using the Deauville 5-point scale and patients were ranked according to the Lugano classification as complete or not complete metabolic responders. The impact of the segmentation method (alternate threshold at 41%) and image resolution (Gaussian postsmoothing of 3, 5, and 7 mm) was investigated. The association of the proposed parameters with early response was assessed in univariate and multivariate analyses. Their added predictive value was explored using supervised classification by support vector machines (SVM). We evaluated in leave-one-out cross-validation three SVMs admitting as input features (a) MTV, (b) MTV + histological type, and (c) MTV + histology + relevant texture/shape indices. RESULTS: Features associated with complete metabolic response were low MTV (P = 0.01), low TLG (P = 0.003), high power spectral density AUC (P = 0.007), high surfacic extension (P = 0.006), low 2D fractal dimension (P = 0.007), and low 3D fractal dimension (P = 0.003). The prognostic value of these metrics was optimal with the 30% segmentation threshold and overall was progressively altered with decreasing image resolution. In cross-validation, the SVM accounting for texture and shape achieved the highest predictive value with ROC AUC of 0.82 and 80% accuracy (compared with 0.68 and 61% for MTV, and 0.65 and 68% for MTV + histology). CONCLUSIONS: The combination of usual prognostic factors with appropriately chosen textural and shape parameters evaluated on baseline PET-CT improves the prediction of early metabolic response in bulky lymphoma.

Long-term persistence of memory B cells specific for hepatitis B surface antigen in HIV-1-infected patients.

To investigate the maintenance of long-term memory B cells specific for hepatitis B surface antigen (HBsAg), purified blood B cells were polyclonally stimulated and cells secreting antibodies directed to HBsAg (HBs-SC) enumerated by ELISpot. HBs-SC were found in 18/20 HIV-1-infected patients with either natural or vaccinal immunity to hepatitis B virus, including six subjects with serum anti-hepatitis B surface antibody levels less than 10 mIU/ml. A lower number of HBs-SC was found in HBsAg-vaccinated patients compared with vaccinated controls.

Detection of memory B lymphocytes specific to hepatitis B virus (HBV) surface antigen (HBsAg) from HBsAg-vaccinated or HBV-immunized subjects by ELISPOT assay.

To improve the investigation of the role of human memory B lymphocytes following hepatitis B virus (HBV) infection or vaccination, we developed a method to characterize circulating memory B cells specific to hepatitis B surface antigen (HBsAg). Our approach combined: (1) purification of CD19+ cells, (2) CD40-CD40L polyclonal stimulation, and (3) enumeration of memory B cells differentiated into anti-HBs antibody (Ab)-secreting cells (HBs-SCs) by a HBs-ELISPOT assay. In this way, HBs-SCs were detected in 17 HBsAg-vaccinated and nine HBV-immunized subjects including four individuals with serum anti-HBs Ab levels < 10 mIU/ml, but not in six controls. IgG+, IgA+ plus IgM+ HBs-SCs, representing 5-1736 cells/10(6) circulating B cells and 0.02-0.58% of total immunoglobulin-SCs generated by the B cell polyclonal stimulation, were counted by an Ig two-colour ELISPOT assay. In addition, anti-HBs Abs were found in 8/15 supernatants recovered from B cell cultures which contained HBs-SCs, suggesting that the HBs-ELISPOT assay is more reliable in tracking HBsAg-specific memory B cells than ELISA measurement of anti-HBs Abs secreted in supernatants. This new approach could be useful to explore the presence and the longevity of HBsAg-specific memory B cells in vaccinated and immunized subjects, in chronic HBV infection and after liver transplantation for HBV-related disease.

Detection of a large T-cell reservoir able to replicate HIV-1 actively in breast milk.

In breast milk and paired blood samples of nine HIV-1-infected lactating women, we undertook a study to detect a CD4 T-cell reservoir and to investigate its capacity to enter viral production after activation. Breast milk-infected CD4 T cells have a greater capacity to produce viral particles actively than blood CD4 T cells. This observation may explain the apparent paradox of a transmissible viral infection from a body fluid with a low viral concentration.