Predictive value of serological tests in rubella virus infection during pregnancy
INTERVIROLOGY
Authors: Pustowoit, B; Liebert, UG
Abstract
In an attempt to define diagnostic criteria that may help to distinguish the congenital rubella syndrome (CRS) from subclinical intrauterine rubella virus (RV) infection, maternal and fetal serum samples were analyzed using (1) enzyme immunoassay employing RV synthetic peptides as antigen, (2) IgG avidity assay, and (3) immunoblot under nonreducing conditions, in addition to hemagglutination inhibition and commercial enzyme immunoassays. Infants born with CRS and their mothers were shown to reveal low or undetectable levels of E2-specific antibodies and deficient IgG recognizing the major neutralizing antibody-inducing epitope on the E1 protein (SP15). Antibody responses were normal in mothers with presumed RV reinfection as well as in asymptomatic infants born after maternal primary rubella. The results indicate that the maturation of specific humoral immune responses is obviously less efficient when intrauterine RV infection results in CRS. The detection of high avidity IgG, conformational E2-specific as well as SP15-reactive antibodies may serve as a potential predictor for a benign outcome of intrauterine RV infections.
CELLULAR HYPERIMMUNOREACTIVITY TO RUBELLA-VIRUS SYNTHETIC PEPTIDES IN CHRONIC RUBELLA ASSOCIATED ARTHRITIS
ANNALS OF THE RHEUMATIC DISEASES
Authors: MITCHELL, LA; DECARIE, D; SHUKIN, R; TINGLE, AJ; FORD, DK; LACROIX, M; ZREIN, M
Abstract
Objectives-Immune recognition of the major structural proteins of rubella virus by peripheral blood mono-nuclear cells and synovial inflammatory infiltrates of a patient with documented chronic rubella associated arthritis was compared with responses of normal healthy rubella virus immunoreactive subjects to establish if there were unusual response patterns associated with rubella associated arthritis in this subject. Methods-Synthetic peptides (16-33 amino acids in length) representing selected amino acid sequences of the rubella virus envelope (E1 and E2) and capsid (C) proteins were used in lymphocyte stimulation assays with peripheral blood mononuclear cells or synovial inflammatory infiltrates to determine T lymphocyte recognition of antigenic sites within the synthetic peptides. A rubella virus specific polymerase chain reaction was used to determine the persistence of rubella virus in the patient's cells. Results-The patient's peripheral blood mononuclear cells showed abnormally increased lymphoproliferative responses to three E1 synthetic peptides encompassing residues 219-234, 389-411, and 462-481, and one E2 synthetic peptide containing the sequence 50-72, of which the last three were predicted to contain T cell antigenic sites. Although the patient's peripheral blood mononuclear cells showed positive proliferative responses to C synthetic peptides, these were not unusual. The number of synthetic peptides within the E1, E2, and C panels recognised by the patient's peripheral blood mononuclear cells was greater than was previously observed in normal healthy subjects. The recognition of synthetic peptides by synovial inflammatory infiltrates was similar to peripheral blood mononuclear cells but the responses measured were lower. The polymerase chain reaction was negative for rubella virus detection in peripheral blood mononuclear cells and synovial inflammatory infiltrates. Conclusions-Abnormally increased T cell recognition of antigenic sites within rubella virus E1 and E2 proteins observed in this patient with rubella associated arthritis suggests chronic antigenaemia due to persistent rubella virus in tissue sites other than peripheral blood mononuclear cells or synovial inflammatory infiltrates.