Natural autoantibodies: Transplacental passage in humans (original) (raw)
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Expression and control of the natural autoreactive IgG repertoire in normal human serum
European journal of …, 1993
We have investigated the autoreactive repertoire expressed by serum IgG of healthy individuals of various age groups using a large panel of self antigens. Natural IgG autoantibodies against all self antigens of the panel were found in the purified IgG fraction of the serum of all donors that were tested. The mean binding activity to self antigens of IgG of pregnant women was higher than that of IgG purified from the serum of infants, young adults and aged individuals. No increase in IgG autoreactivity was observed with aging neither in the purified IgG fraction of serum nor in whole serum. Whereas autoantibody activity was easily detectable in purified IgG, it was low in serum. No difference was observed, however, between the binding activity of purified IgG and of IgG in serum in the case of foreign antigens nor in the case of anti-thyroglobulin autoantibodies of patients with Hashimoto's thyroiditis. Purified IgM from normal serum bound to F(ab')2 fragments of autologous IgG in a dose-dependent fashion and inhibited the binding of autologous IgG to self antigens. Our results thus indicate that autologous IgM contributes to regulate expression of the natural IgG autoreactive repertoire through V region-dependent interactions, resulting in low levels of IgG autoreactivity in serum under physiological conditions.
High frequency of natural autoantibodies in normal newborn mice
The Journal of …, 1985
Spleen cells from 6-day-old nonimmunized BALB/ c and BALB.Bl0 mice were fused with the nonsecreting hybridoma cell line Sp2/0. Three hundred and eighty-four immunoglobulin-secreting hybrids were screened for antibody activity against mouse actin, tubulin, and myosin, and against TNP, peroxidase, renin, DNA, and neurofilanients. At least 24 hybridomas in the collection (6.25%) exhibited antibody activity against this panel of antigens. Ten of these hybrids were cloned, were propagated, and the corresponding monoclonal IgM protein was isolated from ascitic fluids and was further characterized. At least four groups of antibody specificities were identified: 1) one clone reacting with TNP only; 21 one clone reacting with both actin and tubulin; 3) two clones which bound to both TNP and actin; and 4) a fourth group, comprising the six other clones, which all exhibited widespread reactivity and bound to actin, tubulin, myosin, and TNP. These results indicate: 1) B cell clones directed against self antigens are activated in the internal environment and are recovered consequently by somatic cell hybridization: 2) the widespread antibody specificities found for these newborn mouse antibodies are very similar to those previously characterized with human natural antibodies and human monoclonal Ig; and 3) the frequency of B cells binding to cytoskeletal proteins and TNP is very high (at least 6.25%). We have been particularly concerned with the existence, functional role, and significance of "natural antibodies" isolated from normal sera which specifically react with antigenic determinants present on self proteins. In a previous study, we demonstrated the presence of natural antibodies directed against tubulin. actin, thyroglobulin, fetuin, albumin, transferrin, cytochrome c , and collagen in normal human serum (1). We further extended this analysis by studying 612 human monoclonal immunoglobulins (MIg),' and demonstrated a high incidence
A neonatally tolerant mouse model to assess pathogenicity of human autoantibodies
Journal of Immunological Methods, 1990
Since certain autoimmune diseases, including myasthenia gravis and pemphigus vulgaris can be reproduced in mice by passive transfer of immunoglobulins from affected patients, we assessed whether this procedure could be optimised. Repeated injections of human IgG into mice during pregnancy induced tolerance to human IgG in the litter, and this persisted for at least 9 months. We show that three different human autoantibodies, to mitochondria, centromere and collagen, were retained in the serum of neonatally tolerized mice, but pathogenic effects of these particular autoantibodies were not demonstrable over the four week time scale of our experiments. However, our model should be applicable to studies on human autoantibodies which might damage the appropriate tissue in a heterologous species.
Journal of immunology (Baltimore, Md. : 1950), 1995
We have used a quantitative immunoblot technique to analyze the Ab repertoire of IgG in the serum of healthy adults with a large panel of homologous and foreign Ags in tissue extracts. Densitometric patterns of reactivity of purified IgG with self-Ags exhibited striking homogeneity among individuals with regard to the protein bands that were recognized. Purified IgG showed higher levels of reactivity with self-Ags than IgG in whole serum. Reactivity with self-Ags of IgG in whole serum was restricted to a small number of protein bands (fewer than 10). There were significant inter-individual differences in the intensity and nature of immunoreactivities. Purified IgG of different individuals exhibited heterogeneous patterns of immunoreactivity with Ags in bacterial extracts. Comparative analysis of repertoires of IgG and IgM indicated that all protein Ags recognized by IgM were also reactive with purified IgG. Some proteins in homologous and in foreign tissue extracts reacted solely wi...
Proceedings of the …, 1995
Analysis of the reactivity of IgM with selfantigens in tissues by a quantitative immunoblotting technique showed striking invariance among newborns in the human and in the mouse. The self-reactive repertoire of IgM of adults was also markedly conserved; it comprised most anti-self reactivities that prevailed among neonates. Multivariate analysis confirmed the homogeneity of IgM repertoires of neonates toward self-and non-self-antigens. Multivariate analysis discriminated between newborn and adult repertoires for reactivity with two of five sources of self-proteins and with non-self-antigens. Our observations support the concept that naturally activated B lymphocytes are selected early in development and throughout life for reactivity with a restricted set of self-antigens.
Benefits and Risks of IgG Transplacental Transfer
Diagnostics, 2020
Maternal passage of immunoglobulin G (IgG) is an important passive mechanism for protecting the infant while the neonatal immune system is still immature and ineffective. IgG is the only antibody class capable of crossing the histological layers of the placenta by attaching to the neonatal Fc receptor expressed at the level of syncytiotrophoblasts, and it offers protection against neonatal infectious pathogens. In pregnant women with autoimmune or alloimmune disorders, or in those requiring certain types of biological therapy, transplacental passage of abnormal antibodies may cause fetal or neonatal harm. In this review, we will discuss the physiological mechanisms and benefits of transplacental transfer of maternal antibodies as well as pathological maternal situations where this system is hijacked, potentially leading to adverse neonatal outcomes.
Annals of the Rheumatic Diseases, 2011
Background Anti-β 2 -glycoprotein-I (anti-β 2 GPI) were demonstrated to be pathogenic in the antiphospholipid syndrome (APS). However, they can be detected in patients with no features of APS, especially those affected by systemic autoimmune diseases (SAD), and so in healthy children. It has been suggested that anti-β 2 GPI against domain 1 (D1) associate with thrombosis, while those recognising domain 4/5 (D4/5) are present in nonthrombotic conditions. Objective To evaluate the fi ne specifi city of anti-β 2 GPI in adults and infants. Methods Three groups were examined-group A: 57 1-year-old healthy children born to mothers with SAD; group B: 33 children with atopic dermatitis; group C: 64 patients with APS. Subjects were selected based on positive anti-β 2 GPI IgG results. Serum samples were tested for anti-β 2 GPI IgG D1 and D4/5 using research ELISAs containing recombinant β 2 GPI domain antigens. Results Children (A and B) displayed preferential IgG reactivity for D4/5, whereas patients with APS were mainly positive for D1. No thrombotic events were recorded in groups A and B. Conclusions The specifi city for D4/5 suggests that anti-β2GPI IgG production in children born to mothers with SAD is a process neither linked to systemic autoimmunity nor related to the maternal autoantibody status. This unusual fi ne specifi city might, at least partially, account for the 'innocent' profi le of such antibodies.