Safety and tolerability of single intravenous doses of T cell modulatory peptide (TCMP-80) in healthy volunteers.

T Cell Modulatory Peptide (TCMP-80), L-lysine-L-serine, is a synthetic dipeptide structurally related to a selected amino acid sequence in human immunoglobulin G. Based on in vitro and preclinical in vivo testing, TCMP-80 has immunomodulatory properties. This report describes the first administration of TCMP-80 to man in a randomized, double-blind, placebo-controlled, single rising-dose tolerability trial. Healthy male volunteers received TCMP-80 or placebo as a 10-minute intravenous infusion. At weekly intervals, two of four subjects were given TCMP-80; the remaining two received placebo. Each subject could receive only one dose during the study. Dosing started at 0.01 mg/kg and was increased to 0.03, 0.1, 0.3, 1, 3, 6.5, and 10 mg/kg. CBCs, blood chemistries, urinalyses, and lymphocyte subset populations were monitored predose and postdose on Days 1, 5, and 14. Three placebo and three TCMP-80 subjects reported adverse events. Adverse events reported after TCMP-80 administration were mild in nature (headache, dizziness, hematoma at injection site), appeared to be independent of dose, and resolved without medical intervention. No clinically significant alterations in vital signs, physical examination parameters, or clinical laboratory values were observed. Based on the results of this study, TCMP-80 is safe and well-tolerated within the dose range studied when administered as single intravenous infusions. Additionally, this study design represents an approach to assess the safety of an investigational immunomodulatory drug.

Materno-embryonally transferred antibodies precipitate autoimmune thyroiditis in obese strain (OS) chickens.

In Obese strain (OS) chickens the role of maternal antibodies, passively transferred through the egg to the developing chick, was evaluated as a causative factor in the early development of spontaneous autoimmune thyroiditis (SAT). In the egg, passive antibody titers were highest in the yolk and lower in the allantoic fluid and sera of developing embryos. This passage of antibodies was documented by use of radiolabeled antibodies. In dams with high antibody titers, antibodies could be found in the sera of chicks at the time of hatch. Thyroglobulin was absent in the yolk of OS eggs during embryonal life, as compared with its detection in normal eggs. Immune complexes (thyroglobulin-autoantibody) detected in the thyroids of OS, but not CS, chicks at the time of hatch, or earlier, appear to reflect the presence of the maternally transferred antibodies. A pair of crosses between OS chickens, with thyroiditis, and the C strain (CS), without thyroiditis, was made to evaluate the role of transferred antibodies in the pathogenesis of autoimmune disease. When an OS chicken was the dam, maternal antibodies could be passively transferred; when a CS chicken was the dam, no maternal antibodies were present to be transferred. Nevertheless, both hybrids developed full-blown thyroiditis, demonstrating that binding of transferred maternal antibody to thyroglobulin is not a prerequisite for the induction of SAT. However, presence of maternal antibodies precipitated the onset of disease. Immune complexes formed in the embryonic thyroid are likely to participate in early autoimmune disease, although the development of full-blown thyroiditis may await the competency of the chick's immune system to provide the characteristic cellular infiltrate.

Detection of monoclonal antibodies for tumor diagnosis with the use of inhibition of micro-enzyme-linked immunosorbent assay.

A micro-enzyme-linked immunosorbent assay (ELISA) test and an ELISA inhibition test were developed and used to detect 4 monoclonal antibodies potentially useful for serodiagnosis of cancer. The 4 antibodies used in conjunction detected 73% of 71 sera from cancer patients and 8% of 42 sera from normal persons. Separately, the 4 antibodies reacted to tumors from various sites such as lung, breast, colon, stomach, and ovary. The ELISA inhibition assay may be useful for detecting culture supernatants reactive against tumor-associated serum antigens. Eventually, a panel of monoclonal antibodies detecting various tumors may be obtainable.

The effect of individual HLA antigens on graft survival rates in kidney transplant patients.

We have used information available in the UCLA International Transplant Registry to study the effect of HLA antigens on graft survival outcome. All results showed that of all antigens tested, the presence of DRl in the recipient was associated with the highest graft survival rate. There was a positive matching effect for most DR antigens that were either presumed homozygous or heterozygous in the recipient. A regression analysis not only confirmed the association of DR1 and low immune response, but also suggested a greater importance of the DR rather than A or B locus to graft survival rates. Recipients with DR1.5 had the highest survival rates when DR1 was compared with other DR antigens and the heterozygous combinations of the two groups. This suggests that presence of heterozygous DR antigens may have combined effects on graft survival.

Immune complexes in tissues of obese strain (OS) chickens.

Obese strain (OS) chickens develop spontaneous autoimmune thyroiditis (SAT) comparable in many aspects to human Hashimoto's thyroiditis. In a chronologic study on chickens of the Obese strain with B1B1 and B4B4 genotypes, immune and electron dense deposits suggesting immune complexes (IC) were found in the basal lamina of thyroid follicles (BLTF) as early as the time of hatching. The incidence of IC deposition in BLTF increased with age. In some of the chickens studied, thyroglobulin could also be demonstrated in the immune deposits. In addition, IC were also detected in the glomerular basement membrane of kidneys and in basement membranes of cecal tonsils. The early occurrence of IC in tissues of OS chickens suggests a possible primary role of these immune reactants in the pathogenesis of SAT.