Turnover of autologous? 1-antitrypsin in a patient with congenital analbuminemia

Abstract

Despite very low amounts of albumin (1.7 mg/100 ml) the total plasma protein concentration of a patient with congenital analbuminemia was only slightly reduced to 6.3 g/100 ml. The lack of albumin is compensated by high concentrations of many other plasma proteins. Among the plasma proteins measured, alpha 1-antitrypsin showed a particularly high level. To investigate the underlying mechanism of this increase we purified plasma alpha 1-antitrypsin from the patient, labelled it with 125I, and studied its turnover in the analbuminemic patient and two normal volunteers. A half-life of 15 days in the patient compared with 7.5 and 8 days in the normal volunteers was found. The calculated synthesis rate of alpha 1-antitrypsin was about twice as high in the patient as in the controls. Therefore, both a longer half-life and an increased synthesis rate contribute to the high level of alpha 1-antitrypsin in the plasma of the analbuminemic patient.

Congenital analbuminaemia: biochemical and clinical implications. A case report and literature review

“…Reports on vitamins and amino acids in analbuminaemia are scarce and no clinical symptoms due to altered serum levels have been reported [1,3,18,21,37]. In our patient, we found an increased level of vitamin D due to an increased level of vitamin D-binding globulin ( Table 2) and normal amino acid levels.…”

“…Thrombotic events were indeed reported in two cases, but noticing that additional predisposing factors were also present, the events cannot unequivocally be attributed to analbuminaemia [18,37]. In our patient, the marginally increased level of thrombin-antithrombin complex and the normal level of prothrombin fragments 1-2, both parameters of fibrin formation, and the normal level of plasmin-a2-antiplasmin complex, a parameter of fibrinolysis activation, indeed suggest that the promoting and inhibitory factors are in balance ( Table 2).…”

“…The most important compensatory mechanism is an increase in the synthesis of non-albumin proteins, to the effect that the total serum protein level is usually only marginally lower. These other proteins are thought to take over many of albumin's functions [12,21,22,37].…”

Selective blockade of CD28 and not CTLA-4 with a single-chain Fv–α1-antitrypsin fusion antibody

“…␣ 1 -Antitrypsin is an abundant (3 g/L) monovalent plasma protein that has already been used for genetic fusion. 34 In humans it has a half-life of about 8 days, 35 although its half-life is much shorter in rodents. 36 To demonstrate the immunosuppressive potential of scFv28.3-HaaT, we reproduced the biologic activities of the CD28.3 antibody Fab fragments in vitro.…”

Splicing mutation in human hereditary analbuminemia.

“…Genomic DNA was analyzed from both the American Indian girl and a control individual, as well as from a second analbuminemic individual of Swiss ancestry (22,23). The albumin gene from the Swiss individual was previously shown by Southern analysis to be grossly intact (24).…”