Managing costs in primary immunodeficiency: minimal immunophenotyping and three national references.

Our aim was to evaluate the cost-effectiveness of a minimal lymphocyte subset quantification (LSQ) by flow cytometry as the first screening in children with clinically suspected primary immunodeficiency (PID). Two hundred sixty-eight Brazilian patients (0-21 years old) were studied. They were divided by clinical and phenotypical features into those fulfilling criteria for PID (PID phenotype) according to the 2017 International Union of Immunological Societies (IUIS) classification and those not fulfilling these criteria (non-PID phenotype). We evaluated how many patients had values below the 10th percentile for five lymphocyte subsets in peripheral blood, (suggestive of PID) according to reference values for Brazil, Italy and USA. Three lymphocyte subsets (T CD3/CD4, B CD19 and NK CD16/CD56) had p-value < 0.05 and Odds Ratio (OR) indicating a risk at least two times higher for the diagnosis of a PID phenotype. The application of Kappa coefficient (k) on Brazilian vs Italian and Brazilian vs US data sets resulted in k compatible with strong or excellent level of agreement between the three classification systems. The authors conclude that a number of CD3+ /CD4+ , CD19+ and CD16+ /CD56+ (NK) cells in peripheral blood <10th percentile represented a significant risk for the diagnosis of PID in this cohort. Natural killer (NK) deficiency is quite rare and has a very specific clinical profile. So, the analysis of these cells could be requested only in some cases, saving even more costs. The minimal immunophenotyping, with quantification of T CD4+ , CD19+ and in some cases CD16+ /CD56+ cells, may be a useful tool for the first screening of PID, saving costs, especially in developing countries.

Participation of leptin in the determination of the macrophage phenotype: an additional role in adipocyte and macrophage crosstalk.

Macrophages develop into specialized cell types with special functional properties, depending on locally produced stimuli. Adipose tissue macrophages present particular characteristics, such as the M2 cell phenotype, and produce cytokines and chemokines usually produced by M1 cells. Our aim was to study the role of leptin, which is an adipokine produced and released by adipocytes, in the induction of these characteristics in macrophages found in the adipose tissue. Human CD14(+) cells were obtained and maintained in culture with IFN-γ (classical M1 phenotype), IL-4 (alternative M2 phenotype) or leptin for 5 d. Surface marker expression was then analyzed by cytometry. In addition, the release of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1ß, IL-10, IL-1ra, MCP-1, MIP-1α, and RANTES was quantified by ELISA after an LPS stimulus, in the culture supernatant. Macrophages exposed to leptin in culture expressed surface markers that were more similar to the M2 phenotype, but they were able to produce TNF-α, IL-6, IL-1ß, IL-1ra, IL-10, MCP-1, and MIP-1α, as observed for M1 cells. Results suggest that leptin strongly contributes to the phenotype observed in macrophages found in adipose tissue.