The present study shows that reimmunization with tetanus toxoid (tet) caused a transient increase of the human blood plasma cell (PC) pool, detectable from 6th to 15th day postboost, as well as the temporal alteration of several PC features. Labeling of specific PC with FITC-tet C fragment (tetC) allowed kinetics analysis of the tetC+ and tetC− PC, and revealed remarkable differences between them: 1) the kinetics of tetC+ PC occurrence was exponential, and most of them appeared in a narrow time frame (5th to 8th day postboost), whereas the tetC− PC increase was lower (three to five times) and more prolonged (4th to 15th day postboost). 2) The tetC+ PC subset contained a fraction of cycling cells, expressed high levels of DR, CD138, and CD126, and responded to IL-6 by improving their survival and Ig secretion; in contrast, the tetC− PC showed higher CXCR4 and lower DR and CD138, did not respond to IL-6, and contained a fraction of apoptotic cells. 3) Sequential phenotypic analysis revealed maturational changes within the tetC+, but not tetC−, PC subset; sequencing of tetC+ PC IgVH genes showed clear features of Ag selection. 4) The tetC+ PC expressed several times more positive regulatory domain I- binding factor 1/B lymphocyte-induced maturation protein 1 transcription factor than the tetC− PC. 5) The tetC− PC and bone marrow resident PC similarly expressed low DR and high CXCR4, but differed in that the latter exhibited higher levels of CD31, CD138, and positive regulatory domain I- binding factor 1/B lymphocyte-induced maturation protein 1. These findings support the view that tetC+ PC contain bone marrow PC precursors, and tetC− PC probably belong to a removable compartment of aged PC.

Patients with silicosis caused by occupational exposure to engineered stone (ES) present a rapid progression from simple silicosis (SS) to progressive massive fibrosis (PMF). Patient classification follows international rules based on radiology and high-resolution computed tomography (HRCT), but limited studies, if any, have explored biomarkers from routine clinical tests that can be used as predictors of disease status. Our objective was thus to investigate circulating biomarker levels and systemic inflammatory indices in ES silicosis patients whose exposure to ES dust ended several years ago. Ninety-one adult men, ex-workers in the manufacturing of ES, 53 diagnosed with SS and 38 with PMF, and 22 healthy male volunteers (HC) as controls not exposed to ES dust, were recruited. The following circulating levels of biomarkers like lactate dehydrogenase (LDH), angiotensin-converting-enzyme (ACE), protein C reactive (PCR), rheumatoid factor, alkaline phosphatase and fibrinogen were obtained from clinical reports after being measured from blood samples. As biochemical markers, only LDH (HC = 262 ± 48.1; SS = 315.4 ± 65.4; PMF = 337.6 ± 79.3 U/L), ACE (HC = 43.1 ± 18.4; SS = 78.2 ± 27.2; PMF = 86.1 ± 23.7 U/L) and fibrinogen (HC = 182.3 ± 49.1; SS = 212.2 ± 43.5; PMF = 256 ± 77.3 U/L) levels showed a significant sequential increase, not been observed for the rest of biomarkers, in the HC → SS → PMF direction. Moreover, several systemic inflammation indices neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), aggregate index of systemic inflammation (AISI) derived from whole blood cell counts showed significant differences between the HC, SS and PMF groups. All these biomarkers were analyzed using receiver operating characteristic (ROC) curves, and the results provided moderately high sensitivity and specificity for discriminating between ES silicosis patient groups and healthy controls. Our study reveals that some inflammatory biomarkers, easily available from routine blood analysis, are present in ES silicosis patients even several years after cessation of exposure to ES silica dust and they could help to know the progression of the disease.

Early aEEG patterns can be predictive of neurological outcome in the preterm newborn. Low-voltage tracing and absence of SWCs are associated with severe neurological lesions/death.

Human plasma cells (PC) are present in cell suspensions obtained from the tonsil by mechanical disaggregation (PC(MECH)). The present study shows that a collagenase treatment of tonsillar debris remaining after mechanical disaggregation yielded similar proportions of PC (PC(COLL)). Moreover, PC(MECH) were present in suspensions highly enriched in germinal center cells whereas PC(COLL) contained most of the IgA-secreting cells, suggesting their predominant location in follicular and parafollicular areas and connective tissue-rich zones such as tonsil subepithelium, respectively. Tonsil PC(MECH) and PC(COLL) shared the phenotype CD38(high) CD19(+) CD20(low) CD45(high), expressed equivalent amounts of PRDI BF1/Blimp-1 transcription factor, and carried similarly mutated IgVH6 genes. However, they differed in several features. 1) PC(MECH) still expressed the early B cell transcription factor BSAP and were HLA-DR(high); in contrast, PC(COLL) were BSAP(-)and HLA-DR(low). 2) PC(MECH) were CD95(+) and Bcl-2(+/-) whereas PC(COLL) showed CD95(+/-) and Bcl-2(+) expression; in addition, PC(MECH) exhibited increased spontaneous apoptosis. 3) The two PC subsets exhibited distinctive adhesion molecule profiles, since PC(COLL) expressed higher levels of CD31, CD44, and CD49d, but a lower level of CD11a than PC(MECH). These results suggest that PC(MECH) are recently generated, short-living PC, and PC(COLL) constitutes a subset with higher maturity and survival, which resides in connective tissue-rich areas.