D. Faict

Transcortin and α2u-globulin messenger rna activities during turpentine-induced inflammation in the rat

Previously we have shown that the serum concentration of transcortin and alpha 2u-globulin markedly decreases during turpentine-induced inflammation. In the present study transcortin and alpha 2u-globulin mRNA from healthy rats and from animals with inflammation was translated in a rabbit reticulocyte lysate system. Female rats had higher levels of translatable transcortin mRNA than male animals and the level of mRNA for transcortin and alpha 2u-globulin decreased rapidly during inflammation. These results indicate that the sex difference in the serum level of transcortin and the changes in serum transcortin and alpha 2u-globulin during inflammation are mainly determined by differences in the mRNAs in the liver.

Transcortin modulates the effect of cortisol on mitogen-induced lymphocyte proliferation and immunoglobulin production

In the present study we investigated whether transcortin modulates the in vitro effects of cortisol on the proliferation of human peripheral blood mononuclear cells (PBMC) stimulated by different mitogens and on mitogen-induced polyclonal immunoglobulin production. Physiological doses of cortisol (10-1000 nM) strongly inhibited the proliferation of PBMC stimulated by the monoclonal antibody OKT3 or by phytohemagglutinin. Addition of pure cortisol-free transcortin significantly reduced these inhibitory effects in a dose dependent manner. Transcortin (1 microM) caused a 3- to 4-fold reduction of the effects of 100 nM cortisol. Transcortin alone had no influence on the proliferation of stimulated PBMC. Polyclonal immunoglobulin production by PBMC stimulated with pokeweed mitogen was enhanced by physiological does of cortisol. A concentration of 100 nM cortisol caused an increase of immunoglobulin G and M production of 81 and 55% respectively. This effect was abolished by addition of 1 microM transcortin to the cultures, whereas transcortin alone had no effect. These results indicate that an evaluation of the effect of corticoids on lymphoid tissues should be based on the free cortisol level rather than on the total cortisol concentration.

Cortisol-free transcortin: Preparation and effect on mitogen-stimulated lymphocytes

Human cortisol-free transcortin was prepared from charcoal-treated serum. The major purification was achieved by affinity chromatography on an immunoadsorbent column of transcortin antibodies coupled to Sepharose 4B. A further purification on hydroxylapatite yielded pure transcortin with preserved steroid-binding activity. This preparation had no significant influence on the proliferation of human lymphocytes stimulated with phytohemagglutinin, nor did it increase the inhibition of lymphocyte proliferation by cortisol or dexamethasone.

Steroid-carrier proteins in patients with multiple myeloma

Patients with multiple myeloma have transcortin levels lower than normal. This is due in essence to a subgroup of patients producing IGG heavy chains with lambda light chains. Patients producing IGG with predominantly kappa light chains have almost normal transcortin levels. On the other hand, the binding activity of the steroid binding beta globulin (SB beta G) of the kappa type of multiple myeloma is significantly higher than the steroid binding of the lambda type of multiple myeloma. The serum levels of vitamin D binding protein (DBP) fall in the normal range.

Transient high transcortin levels in patients with sputum-positive pulmonary tuberculosis.

SummaryPatients with sputum-positive pulmoray tuberculosis often display during several months a significant increase in serum transcortin levels. This increase is present before tuberculostatic therapy is started and often disappears before the latter treatment is interrupted. Serum estradiol and hemoglobin Aj£ levels were measured in the same blood samples and remained normal. As well withinperson as between-person the transcortin levels did not correlate with the following plasma protein levels or parameters: sedimentation rate, C-reactive protein (CRP), iron binding capacity (IBC), haptoglobin, a,-antitrypsin, a2-macroglobulin, fibrinogen, ceruloplasmin and 5 plasma electrophoretic fractions (albumin, a. <2,/5 and y globulins). On the other hand, the levels of steroid-binding /3 globulin did display changes similar to those observed in the transcortin levels. It remains to be explained why transcortin levels decrease sharply during certain infectious diseases (see reference I) and increase in patients...

Further data on the association of unexplained high transcortin levels with lymphoproliferative malignancies on the one hand and certain HLA haplotypes on the other hand

SummaryThe association of unexplained high transcortin levels with lymphoproliferative malignancies and with certain HLA haplotypes was further explored.

Phylogenetic study of transcortin using monoclonal antibodies

We produced monoclonal antibodies that recognise three distinct epitopes of human transcortin. These epitopes are present on transcortin of humans with normal and altered transcortin levels, as well as on a variant with lower affinity for cortisol. One epitope is present on transcortin of Old World Monkeys and apes, the others are only present on transcortin of apes. The epitopes are not present on transcortin of other species. These results indicate that human transcortin contains a highly evolved and a more conserved part.

More HLA haploidentity in pairs of sibs with the same transcortin levels

In 50 sibships, each comprising at least 2 male sibs, the oldest sib was paired with each of his brothers. All sibs were HLA- haplotyped and their serum transcortin level was determined. The HLA haploidentical pairs were compared with the sibpairs having no HLA haplotype in common. The odds for the haploidentical pairs of having a small difference (less than 0.07 mg per g total serum protein) in serum transcortin was nearly 4 times (3.94; P less than 0.025) greater than for the pairs of brothers having no HLA haplotype in common. This abnormal distribution in HLA haplotypes confirms our previous findings on the relation of certain HLA haplotypes with either high or low basal serum transcortin levels.