Priming with intranasal lactobacilli prevents Pseudomonas aeruginosa acute pneumonia in mice.

BACKGROUND: Increasing resistance to antibiotics of Pseudomonas aeruginosa leads to therapeutic deadlock and alternative therapies are needed. We aimed to evaluate the effects of Lactobacillus clinical isolates in vivo, through intranasal administration on a murine model of Pseudomonas aeruginosa pneumonia. RESULTS: We screened in vitro 50 pulmonary clinical isolates of Lactobacillus for their ability to decrease the synthesis of two QS dependent-virulence factors (elastase and pyocyanin) produced by Pseudomonas aeruginosa strain PAO1. Two blends of three Lactobacillus isolates were then tested in vivo: one with highly effective anti-PAO1 virulence factors properties (blend named L.rff for L. rhamnosus, two L. fermentum strains), and the second with no properties (blend named L.psb, for L. paracasei, L. salivarius and L. brevis). Each blend was administered intranasally to mice 18 h prior to PAO1 pulmonary infection. Animal survival, bacterial loads, cytological analysis, and cytokines secretion in the lungs were evaluated at 6 or 24 h post infection with PAO1. Intranasal priming with both lactobacilli blends significantly improved 7-day mice survival from 12% for the control PAO1 group to 71 and 100% for the two groups receiving L.rff and L.psb respectively. No mortality was observed for both control groups receiving either L.rff or L.psb. Additionally, the PAO1 lung clearance was significantly enhanced at 24 h. A 2-log and 4-log reduction was observed in the L.rff + PAO1 and L.psb + PAO1 groups respectively, compared to the control PAO1 group. Significant reductions in neutrophil recruitment and proinflammatory cytokine and chemokine secretion were observed after lactobacilli administration compared to saline solution, whereas IL-10 production was increased. CONCLUSIONS: These results demonstrate that intranasal priming with lactobacilli acts as a prophylaxis, and avoids fatal complications caused by Pseudomonas aeruginosa pneumonia in mice. These results were independent of in vitro anti-Pseudomonas aeruginosa activity on QS-dependent virulence factors. Further experiments are required to identify the immune mechanism before initiating clinical trials.

A case of IgE myeloma transformed into IgE-producing plasma cell leukaemia.

This is a case report of a challenging diagnosis of IgE monoclonal gammopathy of undetermined significance, which transformed into myeloma, then transformed into IgE-producing plasma cell leukaemia in a 71-year-old male who was followed in Brest, France, from 2015 to 2019. The IgE-producing variant is the rarest sub-type of multiple myeloma, and plasma cell leukaemia is considered to be the rarest and the most aggressive of human monoclonal gammopathies. In November 2015, hypogammaglobulinemia was detected during a systematic check-up. A kappa light chain monoclonal gammopathy was first diagnosed due to an increase of the free kappa/lambda light chains ratio. No monoclonal immunoglobulin was detected by either serum protein electrophoresis (Capillarys 2, Sebia, Issy-les-Moulineaux, France) or immunofixation (Hydrasys 2, Sebia, Issy-les-Moulineaux, France). In June 2018, a blood smear led to the diagnosis of plasma cell leukaemia. A monoclonal peak was detected and identified as IgE-kappa. Analysis of an archival sample taken three years earlier, revealed the presence of a monoclonal IgE, which had been missed at diagnosis. Chemotherapy with bortezomib and dexamethasone was introduced. The patient survived 10 months after the diagnosis of leukaemia. This case shows that an abnormal free light chain ratio should be considered as a possible marker of IgE monoclonal gammopathy even in the absence of a solitary light chain revealed by immunofixation. In addition, the use of an undiluted serum may increase the sensitivity of the immunofixation for the detection of IgE monoclonal gammopathies compared to the 1:3 dilution recommended by the manufacturer.

Is capillary zone electrophoresis a suitable method for estimating serum albumin: A comparison of four methods.

BACKGROUND: The capillary zone electrophoresis method of albumin measurement is frequently used for oncologic and haematologic patients but few data exist about the agreement between the albumin measurements performed by capillary zone electrophoresis and other methods. The aim of this study was to analyse the agreement between human serum albumin measurements by capillary zone electrophoresis and by the nephelometry, bromocresol purple and turbidimetry methods. METHOD: We prospectively measured 100 freshly collected non-frozen patient serum samples, by using four different methods: the capillary zone electrophoresis method performed with a CAPILLARYS 2 instrument, the bromocresol purple dye method performed with an Advia XPT analyser, the nephelometric method performed with a BN ProSpec analyser and the turbidimetric method with reagents from DiAgam and performed with the Advia XPT analyser. RESULTS: A bias towards higher values in the lower range of albumin concentrations was observed with capillary zone electrophoresis compared to immunonephelometry: correlation coefficient r2 = 0.925; slope of 0.86 (0.82-0.89, 95% confidence interval), which is significantly different from 1; and an intercept of 4.94 g/L (3.67-6.16, 95% confidence interval). Similar results were observed when comparing capillary zone electrophoresis to the bromocresol purple and immunoturbidimetry methods. The capillary electrophoresis method overestimated low albumin levels by up to 25% (5 g/L). CONCLUSION: Compared to the nephelometry, turbidimetry and bromocresol purple methods, the capillary zone electrophoresis method tends to overestimate human serum albumin concentrations for levels below 30 g/L. This discrepancy could lead to an overestimation of the nutritional status, an inappropriate scoring of the disease and a delay in nutritional treatment.