Diagnostic value of CD45RO expression on circulating T lymphocytes of fetuses and newborn infants with pre-, peri- or early post-natal infections

Abstract

SUMMARYWe examined the expression of the CD45RO antigen, which characterizes the antigen primed/memory phenotype of T lymphocytes, as a marker for congenital infection in blood samples of newborns and fetuses. CD45RO expression on T cells was determined by triple-colour fluorescence flow cytometry. In total 537 blood samples of newborns and infants up to an age of 3 months and 89 fetal blood samples from gestational weeks 19-31 were analysed. Of the newborns and infants, 74 had a clinically, serologically and/or antigenically evident infection, and four of the fetuses had a confirmed intra-uterine infection. In 35 infants with acute predominantly bacterial infections such as sepsis or pneumonia, 17 (48 . 6%) had elevated CD45RO bright expression. In 39 infants with proven pre-, peri-or early post-natal infections with toxoplasmosis, cytomegalovirus (CMV), rubella, herpes simplex virus (HSV) or human herpes virus type 6 (HHV6), 25 (64 . 1%) exhibited enhanced CD45RO bright expression. Three of four fetuses with confirmed intra-uterine infection (three with CMV, one with parvovirus B19) exhibited elevated CD45RO bright expression. The specificity of the CD45RO assay for detecting microbial infections was 94 . 6% for newborns and infants up to 3 months and 90 . 6% for fetuses. It is concluded that elevated numbers of CD45RO bright T cells in infants up to 3 months of age strongly suggest an infection. However, the sensitivity of the CD45RO assay is not sufficient to enable the test to be used as a general marker for prescreening infants to detect pre-, peri-or early post-natally acquired infections.

Polyunsaturated fatty acids and T‐cell function: Implications for the neonate

“…The lower number of CD45RO + T cells, compared with the full-term infant, likely contributes to the higher susceptibility to infection in these high-risk infants (43). Consistent with the lower proportion of memory/antigen-mature T cells, we found that at 42 d of age, the proportion of CD4 + CD45RA + cells in preterm infants was higher (33) than that in the literature for full-term infants (2,34,39,64). Contrary to that reported in adults (41) and fullterm infants, after 3 mon of age (39,64), ~10-20% of peripheral CD4 + and CD8 + cells in 42-d-old preterm infants did not express either of the CD45 isoforms (33).…”

“…In the infant, the most frequently studied markers that delineate antigen naïve and mature T cells are the variant isoforms of CD45 (the common lymphocyte antigen), the CD45RA isoform (molecular weight 190,000-220,000), and the CD45RO isoform (molecular weight 180,000). CD45RO + T cells are believed to identify primed/memory (antigeneducated) cells and are derived from CD45RA + (naïve) cells after antigenic or mitogenic stimulation (34). The CD45RA antigen is first expressed late during intrathymic maturation and continues to be expressed by most circulating T cells in the infant (35)(36)(37).…”

“…With age, CD4 + CD45RA + cells have been shown to differentiate into CD4 + CD45RA − /CD45RO + "memory" cells. These "primed/memory" cells are the predominant isoform of expressed T cells in the adult (30-40% of adult CD4 + and CD8 + cells) and convey most of the functions associated with T cells (2,34,35,(38)(39)(40).…”

Unexplained fetal death is associated with changes in the adaptive limb of the maternal immune response consistent with prior antigenic exposure

“…The expression of CD45 isoforms has been proposed as a potential marker for the diagnosis of perinatal infection and allograft rejection [20][21][22][23] . Hodge and co-workers 19 reported that all neonates with proven bacterial or viral infection had an increased number of either CD45RO+ cells (50%) or the dual expression cells CD45RA+/CD45RO+ (88%) at birth.…”

“…In contrast, in cases of viral infection, a high percentage of CD45RO+ cells persisted for at least 12-20 weeks 19 . Also, changes in the proportion of CD45RO+ and/or CD45RA+ cells in peripheral blood of adults have been observed in several chronic conditions, such as psoriasis 24 , rheumatoid arthritis 25 , atopic asthma 26 , human immunodeficiency virus infection 27,28 and renal allograft rejection 20,21,23 . Table 4 Correlation coefficient (Pearson correlation) among the study markers and gestational age (GA) at blood sampling in normal pregnant women (n = 89) The results of this study indicate that women with a fetal death had a higher percentage of CD45RO+ cells ('memory-like' T cells) and a lower proportion of CD45RA+ cells ('naive-like' T cells) in the CD4+ subset of lymphocytes than normal pregnant women.…”