SERUM CONCENTRATION OF HUMAN ALPHA2 HS GLYCOPROTEIN DURING THE INFLAMMATORY PROCESS - EVIDENCE THAT ALPHA2 HS GLYCOPROTEIN IS A NEGATIVE ACUTE-PHASE REACTANT

A nonspecific opsonin function has ben ascribed to human alpha2 HS glycoprotein. Its serum level has been shown to be decreased in trauma patients. Recent studies from this laboratory revealed a heterogeneity among the final products obtained in the course of the preparation of the protein. To data, no definitive agreement existed with regard to a molecular homogenous entity of alpha2 HS glycoprotein (Ba-alpha2 glycoproteins). The purpose of the current work was to study the variations in serum level of alpha2 HS in patients suffering from an acute inflammatroy process of bacterial etiology and to determine whether a decrease in alpha2 HS was accompanied by the apperance of fragments of this protein in the serum. A method of preparing alpha2 HS was thus developed, using an immune adsorbent as a final purification step. In an intermediary step of the preparation, alpha2 HS was found to bind zinc ions when metal chelate affinity chromatography was employed. Immunologically and physico-chemically pure alpha2 HS was obtained. The protein consists of a unique polypeptide chain of about 50,000 daltons and has a unique amino-terminal residue, alanine. However, the protein maintained its molecular integrity with difficulty, and spontaneous fragments ranging from 30,000 to <10,000 daltons were produced in some of the preparations. No major modification in the molecular structure of the protein was noted in the sera of subjects suffering from an acute inflammatory process. Serum level of alpha2 HS and alpha1 antitrypsin (AT) was determined in 23 patients. When the acute-phase (AP-)reactent alpha1 AT was increased (difference with normal mean > +2 or +3SD), the sera showed a large decrease in alpha2 HS (difference with normal mean <-2 or -3 SD). The serum level of alpha2 HS, albumin, alpha2 macroglobulin, and positive AP-reactants, orosomucoid, alpha1 AT, haptoglobin, and ceruloplasmin was evaluated in a longitudinal study of seven patients. The results were submitted to a principal components analysis. Alpha2 HS showed a negative correlation with the AP-reactants alpha1 AT, orosomucoid, and haptoglobin (P < 0.05) and a positive correlation with albumin (P < 0.05); these findings indicate that alpha2 HS is a negtive AP-reactent. In addition, analysis of the principal components confirms the strong analogy between alpha2 HS and albumin and indicates that serum level behavior of the AP-reactants during the course of the disease closely depends on the protein studied.