Modulation of natural IgM autoantibodies to oxidative stress-related neo-epitopes on apoptotic cells in newborns of mothers with anti-Ro autoimmunity.
At birth, the human immune system already contains substantial levels of polymeric IgM, that include autoantibodies to neo-epitopes on apoptotic cells (ACs) that are proposed to play homeostatic and anti-inflammatory roles. Yet the biologic origins and developmental regulation of these naturally arising antibodies remain poorly understood. Herein, we report that levels of IgM-antibodies to malondialdehyde (MDA) protein adducts, a common type of in vivo generated oxidative stress-related neoepitope, directly correlate with the relative binding of neonatal-IgM to ACs. Levels of IgM to phosphorylcholine (PC), a natural antibody prevalent in adults, were relatively scant in cord blood, while there was significantly greater relative representation of IgM anti-MDA antibodies in newborns compared to adults. To investigate the potential interrelationships between neonatal IgM with pathogenic IgG-autoantibodies, we studied 103 newborns born to autoimmune mothers with IgG anti-Ro (i.e., 70 with neonatal lupus and 33 without neonatal lupus). In these subjects the mean levels of IgM anti-Ro60 were significantly higher than in the newborns from non-autoimmune mothers. In contrast, levels of IgM anti-MDA in IgG anti-Ro exposed neonates were significantly lower than in neonates from non-autoimmune mothers. The presence or absence of neonatal lupus did not appear to influence the total levels of IgM in the anti-Ro exposed newborns. Taken together, our studies provide evidence that the immune development of the natural IgM-repertoire may be affected, and become imprinted by, the transfer of maternal IgG into the fetus.
Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY 10016, USA; Department of Medicine, Unit of Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Caroline
C
Grönwall
Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY 10016, USA.
Robert M
RM
Clancy
Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY 10016, USA.
Lelise
L
Getu
Department of Medicine, Unit of Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Katy A
KA
Lloyd
Department of Pathology and Laboratory Medicine, Division of Transfusion Medicine & Therapeutic Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Don L
DL
Siegel
Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY 10016, USA.
Joanne H
JH
Reed
Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY 10016, USA.
Jill P
JP
Buyon
Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: gregg.silverman@nyumc.org.
Gregg J
GJ
Silverman
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005333:Fetus / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D007231:Infant, Newborn; D008315:Malondialdehyde / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D009035:Mothers; D018384:Oxidative Stress / Q000276:immunology*; D010767:Phosphorylcholine / Q000009:adverse effects / Q000097:blood; D011247:Pregnancy; D011248:Pregnancy Complications; D012261:Ribonucleoproteins / Q000737:chemistry / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012261:Ribonucleoproteins; C048844:anti-IgG; C024242:polymeric IgM; D010767:Phosphorylcholine; D008315:Malondialdehyde
Malondialdehyde; Maternal IgG; Neonatal immunity; Neonatal lupus; Repertoire