Role of Copeptin in Predicting Postoperative Hyponatremia and Hypernatremia in Patients Undergoing Endoscopic Pituitary Adenoma Surgery.

BACKGROUND AND OBJECTIVES: Arginine vasopressin (AVP) is an important hormone responsible for maintaining sodium homeostasis after pituitary surgery. The measurement of AVP levels is difficult because of its short half-life (t1/2). Copeptin is a preprohormone of AVP, and it is a more stable peptide, which can be used as surrogate marker for AVP. This study aims to assess the role of copeptin as a predictor of postoperative hyponatremia and hypernatremia in patients undergoing endoscopic pituitary adenoma surgery. METHODS: This prospective study included 50 patients who underwent endoscopic pituitary adenoma surgery. Serum copeptin levels of these patients were assessed (1) preoperatively (C1), (2) at extubation (C2), and (3) postoperative day 4 (C3). Perioperative data regarding fluid and sodium balance were collected from patients. Statistical analysis was done using the above data. RESULTS: The copeptin values were assessed against the sodium disturbances. 100% of patients who developed transient diabetes insipidus had a relative decrease in C2 from C1 (P - .0002). 88% of patients who developed early hyponatremia had a relative increase in C2 as compared with C1 (P < .01). 75% of patients who developed delayed hyponatremia had a relative increase in C3 as compared with C1 (P = .003). CONCLUSION: A relative increase or decrease in early change in copeptin (C2-C1) can predict development of early hyponatremia or transient central diabetes insipidus, respectively. A relative increase in delayed change in copeptin (C3-C1) can predict development of delayed hyponatremia.

Anti-α-galactoside and Anti-ß-glucoside Antibodies are Partially Occupied by Either of Two Albumin-bound O-glycoproteins and Circulate as Ligand-binding Triplets.

Two heavily O-glycosylated proteins and albumin co-purified with anti-α-galactoside (anti-Gal), the chief xenograft-rejecting antibody and anti-ß-glucan (ABG) antibody isolated from human plasma by affinity chromatography on respective ligand-bearing matrices. Both antibodies and O-glycoproteins co-purified with plasma albumin eluted from albumin-specific matrix. Using components of affinity-purified antibody samples separated by electrophoresis binding of either albumin or antibody to the affinity matrix of the other or binding of O-glycoprotein to either matrix was ruled out. Enzyme-linked immunoassay and ligand-induced fluorescence enhancement of fluorolabeled antibody showed that O-glycoproteins occupied sugar-binding sites of anti-Gal and ABG. Neither antibody recognized albumin. O-Glycoprotein-albumin complexes free in plasma, or released from antibodies by specific sugars, were captured on microwell-coated O-glycan-specific lectin jacalin and detected using labeled anti-albumin. We conclude that circulating anti-Gal and ABG form protein triplets in which either O-glycoprotein bridges between antibody and albumin by binding simultaneously to both. Bound albumin restricted O-glycoprotein occupation on antibodies enabling triplets to bind other ligands using spared binding sites. Free anti-Gal and ABG were undetectable in plasma. Jacalin treatment, but not de-O-glycosylation of O-glycoproteins abolished their recognition by anti-Gal or ABG indicating that antibodies recognized serine- and threonine-rich peptide sequences that underlie the O-glycans and are reported surrogate ligands for anti-Gal. The albumin- and antibody-binding O-glycoproteins AOP1 and AOP2 were single polypeptide proteins of size 107 kDa and 98 kDa, containing 54% and 51% carbohydrate respectively and conformed to no known plasma protein in properties. Prospects of triplet-mediated modulations in autologous tissues expressing antibody ligands are discussed.

Plasma anti-α-galactoside antibody mediates lipoprotein(a) binding to macrophages.

Lipoprotein (a) [Lp(a)] is the dominant lipid in atherosclerotic plaques though it is much less numerous than LDL or HDL in circulation. Molecular mechanism of selective uptake of Lp(a) into macrophages is unclear. Lp(a) was reported to form circulating immune complexes with the IgG-dominated plasma anti-α-galactoside antibody (anti-Gal) using the serine- and threonine-rich peptide sequences ( STPS) on its apo(a) subunit as surrogate ligand but left the other binding site of antibody free. We examined if these monovalent immune complexes could bind to smaller STPS-containing molecules on macrophage surface. Using placental membrane O-glycosylated proteins (PMOP) isolated by lectin affinity chromatography as model it was shown that human cell surface glycoproteins were small enough to occupy both binding sites of anti-Gal since they increased the fluorescence of FITC label at Fc part of anti-Gal and inhibited binding of anti-Gal and Griffonia simplicifolia lectin of similar specificity to immobilized ligands. Pre-incubation with anti-Gal facilitated Lp(a) attachment to macrophages unless anti-Gal-specific sugar was present. Anti-Gal-mediated attachment of apo(a) to macrophages increased with the number of apo(a) subunits. Further, anti-Gal-mediated binding of the same sample of apo(a) increased with the specific activity of anti-Gal sample. Finally binding of anti-Gal and anti-Gal-apo(a) complex to PMOP and macrophages respectively was mostly inhibited by LDL suggesting STPS as major anti-Gal epitopes on the cell surface. Results indicated that circulating Lp(a)-anti-Gal immune complexes anchor on macrophages using STPS-bearing cell surface glycoproteins as ligands and offer a pathway for Lp(a) sequestration into macrophages.

Human plasma anti-α-galactoside antibody forms immune complex with autologous lipoprotein(a).

Anti-α-galactoside antibody (anti-Gal) from human plasma that bound to α-galactoside-bearing guar galactomannan gel and was eluted with specific sugar (affinity-purified anti-Gal ; APAG) invariably contained apo(a) and apo B subunits in a proportion close to that in plasma lipoprotein(a) [Lp(a)]. Since LDL does not contain apo(a), result suggested Lp(a) as a component of APAG. Lp(a) in APAG was complexed with anti-Gal since plate-coated anti-apo(a) captured Lp(a) along with the antibody. Association of Lp(a) with anti-Gal in APAG was considerably lower in presence of anti-Gal-specific sugar, suggesting that Lp(a) occupied the sugar-binding site of anti-Gal. Content of Lp(a)-bound anti-Gal in APAG, though a minor fraction of total antibody, increased steadily with total Lp(a) content of plasma. Further, Lp(a) released from immune complex-rich fraction of plasma by anti-Gal- specific sugar was proportional to total plasma Lp(a). Anti-Gal titre decreased with increasing Lp(a) concentration among 114 plasma samples. Results indicate the potential of anti-Gal molecules with its binding site partially occupied by Lp(a) molecule(s) to a) use the remaining binding site(s) to recognize other macromolecules or cells and b) transport Lp(a) across Fc receptor-bearing cells.

apoB-independent enzyme immunoassay for lipoprotein(a) by capture on immobilized lectin (jacalin).

Enzyme immunoassay for lipoprotein(a) [Lp(a)] using antibodies to both apoB and apo(a) subunits (a-B assay) is shown to be affected by differential masking of apoB by apo(a) and the presence of LDL-Lp(a) adducts. An apoB-independent immunoassay by capturing Lp(a) through its O-glycans on microplate-coated lectin jacalin and quantitation using peroxidase-labeled anti-apo(a) (J-a assay) is described. J-a assay response is linear, more than twice as sensitive as a-B assay, and is suppressed only 18 ± 5% by non-Lp(a) O-glycan-containing proteins of serum. Wide variations in IgA did not significantly affect Lp(a) binding to jacalin (CV = 6.4%).