The Contribution of Thyroxine - Binding Prealbumin to the Binding of Thyroxine in Human Serum , as Assessed by Immunoadsorption KENNETH

KTBPA, 2.3 X 108; and KTBG, 1.7 X 1010. t Deceased 26 January 1968. Received for publication 12 November 1968 and in revised form 7 February 1968. INTRODUCTION The existence of L-thyroxine (T4)-binding prealbumin (TBPA) as a normal constituent of human serum has been satisfactorily demonstrated both by a variety of electrophoretic techniques and by its isolation from human serum (1-3). Nevertheless, the proportion of endogenous T4 in serum that is normally bound by TBPA is uncertain because this has been assessed only by electrophoretic methods, which give highly variable results depending upon the method employed. For example, of an essentially endogenous concentration of T4, about 30% migrates with TBPA in agar gel at pH 7.4 (4), 30-45% migrates with TBPA in filter paper at pH 8.6 (5), while in starch gel values which vary from 10-60% have been reported (6-8). Furthermore, in addition to the uncertainty concerning the proportion of endogenous T4 that is bound by TBPA, the relative influence of TBPA on the proportion of free or unbound T4 in human serum is not known. In some ill patients, or after the administration to patients or the addition to serum of certain drugs, there occur a decrease in the T4-binding activity of TBPA and an increase in the proportion of free T4 (9, 10). In the sera of ill patients, a good correlation has been shown to exist between the extent of decrease in T4-binding by TBPA and the extent of increase in the proportion of free T4 (9); nevertheless, a simple cause and effect relationship cannot be assumed. Similarly, in the case 1710 The Journal of Clinical Investigation Volume 47 1968 of drugs, the possibility that their effect on the proportion of free T4 is partly due to an effect on other proteins has not been definitely excluded (10). Consequently, we sought a means for selectively removing TBPA from normal serum without affecting the concentration or activity of the other T4-binding proteins. We achieved this by the addition to human serum of gamma globulin derived from a rabbit antihuman prealbumin antiserum, thereby taking advantage of both the specificity of immunological interactions and the virtual inability of gamma globulin to bind T4. This technique has enabled us to study the specific contribution of TBPA to the binding of T4 in normal and abnormal human sera.