The reverse enzyme-linked immunospot assay was modified to enumerate peripheral blood mononuclear cells (PBMC) secreting IgG1-4, IgA1-2, and IgM. Anti-human IgG F(ab')2 and mouse monoclonal antibodies specific to each of the isotypes were used as solid-phase capture antibodies and developing antibodies, respectively. Although attempts were also made to detect IgD- and IgE-secreting cells (SC), their numbers in the peripheral blood were too few to be reliably estimated. The assay was applied to study healthy subjects including 21 neonates within 3 days of birth, 44 1- to 48-month-old children, and 32 adults. Sixty percent of these neonates had IgM SC in small numbers (less than 20 per 10(6) PBMC), but only three neonates had IgSC of other isotypes. In contrast, by 1-2 months of age children had IgSC of all isotypes, including IgA2 and IgG4, often in higher numbers than adults. The relative frequencies of IgSC were IgA1 greater than IgG1 greater than IgM greater than IgG2 greater than IgG3 greater than IgG4 greater than IgA2 in the children and IgA1 greater than IgG1 greater than IgA2 greater than IgM greater than IgG4 greater than IgG2 greater than IgG3 in the adults. The order of the serum concentrations in the adults was IgG1 greater than IgG2 greater than IgA greater than IgM greater than IgG4 greater than IgG3. No correlation was found between the serum level and the IgSC number of individual isotypes (except for serum IgA and IgA1-SC). This new methodology should facilitate investigating the current status of immunoglobulin synthesis and the Ig repertoire in adults and children, in health and in disease.
"On the other hand, if infected in utero, at birth or soon thereafter, the fetus/infant can produce all classes of Ig, as well as antibodies to specific protein antigens they encounter. Using ELISPOT technology (Lee et al. 1991) we found that, even 6 months-gestation live newborns can produce high numbers of IgG-, IgM-and IgA-secreting cells and protein antibodysecreting cells to syphilis (Stoll et al. 1993). ELISPOT technology (Lee et al. 1989) measures the circulating B cell components of the infant's blood which are in the process of producing Ig and antibodies. "
[Show abstract][Hide abstract] ABSTRACT: Proof of causality of most neuromental disorders (NMD's) is largely unavailable. Lessons from four-decade investigations of the epidemiology, immunology, pathogenesis, prevention and therapy of perinatal infectious agents, which invade directly the nervous system, have led us to propose a new indirect effect hypothesis: maternal transplacentally-acquired antibodies, to agents with epitope molecular mimicry with the developing nervous system, can cross the fetus/infant's blood-nervous system barriers to cause NMD's, clinically manifest years later. Further rationale is provided by relevant evolutionary/developmental (EVO-DEVO) considerations - applicable also to some vaccines. The hypothesis is being tested in: (a) older pregnancy studies with available maternal and newborn sera, and follow-up of the progeny for NMD's; and (b) NMD registry individuals linked to their stored newborn blood spots. Preliminary results support a possible role for schizophrenia of high-tittered antibodies to some agents (toxoplasma, influenza and herpes simplex type 2 virus). A model that includes likely genetic and postnatal influences is schematized and a list of putative agents and factors, based on varying rationales, is tabulated. In case pilot studies are confirmed, the identified agent(s) and antibodies would need to be tested in new prospectively enrolled pregnant women, so as to establish further risk factors leading to possible preventive modalities.
[Show abstract][Hide abstract] ABSTRACT: The development of quantitative single-cell immunoassays has provided a novel opportunity to demonstrate the isotype-specific immunoglobulin responses in normal and infected neonates. The reverse enzyme-linked immunospot assay was used to determine the number of immunoglobulin-secreting cells (IgSCs) in peripheral blood. Baseline numbers of IgSCs were established in 69 uninfected term and preterm infants within 5 days of birth; values above the 99th percentile were considered elevated. The IgSCs were also measured in 266 infants with proved or suspected infections or congenital anomalies. A subset of newborn infants was retested weekly. Few IgSCs (mostly IgMSCs) were detected within 5 days of birth in uninfected neonates, but by 1 month 77% had increased numbers of IgSCs, primarily IgASCs. Sixty-three (24%) of 266 study infants had increased IgSCs on initial sampling (predominantly IgMSCs); these included infants as immature as 25 to 27 weeks of gestational age; elevations in IgSCs were most frequent in infants with intrauterine infections. Increased numbers of IgSCs were uncommon in infants with early-onset sepsis in the first 5 days but were frequent by the second week, consistent with acquisition of infection near the time of delivery. We conclude that the presence of elevated numbers of IgSCs soon after birth may be a useful surrogate marker of untreated intrauterine infection. The development of predominantly IgASCs in the first month of life suggests postnatal exposure to common mucosal antigens.
[Show abstract][Hide abstract] ABSTRACT: Evidence is presented that the percentage and number of some subsets of T and B cells in normal children and adults vary greatly from those in fetal life and throughout the first few years after birth, and less so during adolescence and adulthood. Depending then on the age at which immunological studies are performed, as well as whether the HIV infection occurs in utero, at birth, or postnatally, values obtained by immunophenotypic analyses of differentiating or mature immunocytes will vary greatly. A concerted effort needs to be made to measure different developmental and activation immunophenotypic markers, from birth on, in premature and full-term infants of varying socioeconomic and ethnic background. Results from such studies should improve our ability to determine the timing of HIV infection, to obtain earlier guidelines for prophylaxis or treatment of the virus or of opportunistic infections, as well as to improve prognostic capabilities in perinatal HIV infection.
Clinical Immunology and Immunopathology 05/1994; 71(1):2-7. DOI:10.1006/clin.1994.1043
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