Big data-based parathyroid hormone (PTH) values emphasize need for age correction.

PURPOSE: We aimed to study the relationship between aging and increased parathyroid hormone (PTH) values. METHODS: We performed a retrospective cross-sectional study with data from patients who underwent outpatient PTH measurements performed by a second-generation electrochemiluminescence immunoassay. We included patients over 18 years of age with simultaneous PTH, calcium, and creatinine measurements and 25-OHD measured within 30 days. Patients with glomerular filtration rate < 60 mL/min/1.73 m2, altered calcemia, 25-OHD level < 20 ng/mL, PTH values > 100 pg/mL or using lithium, furosemide or antiresorptive therapy were excluded. Statistical analyses were performed using the RefineR method. RESULTS: Our sample comprised 263,242 patients for the group with 25-OHD ≥ 20 ng/mL, that included 160,660 with 25-OHD ≥ 30 ng/mL. The difference in PTH values among age groups divided by decades was statistically significant (p < 0.0001), regardless of 25-OHD values, ≥ 20 or ≥ 30 ng/mL. In the group with 25-OHD ≥ 20 ng/mL and more than 60 years, the PTH values were 22.1-84.0 pg/mL, a different upper reference limit from the reference value recommended by the kit manufacturer. CONCLUSION: We observed a correlation between aging and PTH increase, when measured by a second-generation immunoassay, regardless of vitamin D levels, if greater than 20 ng/mL, in normocalcemic individuals without renal dysfunction.

Enhanced expression of Fc alpha receptor I on blood phagocytes of patients with gram-negative bacteremia is associated with tyrosine phosphorylation of the FcR-gamma subunit.

Sepsis caused by gram-negative bacteria is a common finding having high incidence and mortality. Fc alpha RI (CD89), a receptor for immunoglobulin A (IgA), has been shown to mediate bacterial phagocytosis, which might play a role in the pathogenesis of sepsis. In this study the expression and function of Fc alpha RI were analyzed on blood monocytes and neutrophils of patients with bacteremia. We found a marked increased in expression of the alpha- and gamma-subunits of the Fc alpha RI on both types of cells in patients with gram-negative bacteremia, but not in patients with gram-positive bacteremia. This increase was independent of serum IgA levels. Fc alpha RI M(r) was lower on cells from gram-negative patients than on cells from controls (50-65 kDa versus 55-75 kDa), despite a similar 32-kDa backbone, indicating altered glycosylation. Increased levels of Fc alpha RI on blood phagocytes correlated with enhanced serum IL-6 levels, but not with IFN gamma or TNF-alpha. FcR-gamma chain associated with Fc alpha RI was phosphorylated in patients neutrophils, indicating functional engagement of this receptor during gram-negative sepsis. Increased expression and activation of Fc alpha RI-gamma 2 complexes following gram-negative infections suggests its involvement in host defense against bacteria.

Impaired expression of IgA Fc receptors (CD89) by blood phagocytic cells in ankylosing spondylitis.

OBJECTIVE: Expression of IgA Fc receptors (CD89, FcalphaR) and their occupancy by endogenous IgA were studied on blood monocytes and neutrophits to determine if FcalphaR defects could account for enhanced serum IgA and IgA-IC commonly found in patients with ankylosing spondylitis (AS). METHODS: Peripheral blood samples were obtained from 34 patients with AS, 15 patients with rheumatoid arthritis, and 34 healthy individuals. Cell surface FcalphaR was analyzed using a quantitative flow cytometry method in which blood cells were stained with anti-FcalphaR monoclonal antibodies recognizing epitopes outside the IgA binding site and with F(ab')2 fragments of anti-IgA antibodies. Modulation of cell surface FcalphaR was evaluated after incubation of blood cells at 37 degrees C in absence of plasma. Biochemical characterization of iodinated FcalphaR molecules was determined by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: FcaR expression was significantly decreased on monocytes and neutrophils in patients with AS compared to control groups. FcalphaR levels were inversely correlated with serum IgA, suggesting its negative regulatory role. Modulation experiments resulted in rapid and higher FcalphaR upregulation in AS than in controls, indicating that these molecules were downregulated only at the cell surface. Moreover, analysis of the surface iodinated FcalphaR molecules by SDS-PAGE revealed higher Mr (60-90 kDa) in AS than controls (55-75 kDa), also suggesting an altered glycosylation. Analysis of receptor occupancy revealed high levels of endogenous IgA bound to monocytes and neutrophils in patients with AS, pointing to a saturation of IgA Fc receptors. CONCLUSION: We observed impaired expression of FcalphaR in patients with AS that is characterized by a downregulation process associated with post-translational alterations and enhanced binding of endogenous IgA. These alterations might lead to a defective blood clearance by FcalphaR resulting in the enhancement of IgA and IgA-IC in AS patients. Decreased FcalphaR expression represents a new marker for this disease.