ABSTRACT
BACKGROUND: After years of periconceptional folic acid supplementation, the prevalence of neural tube defects (NTDs) remains stable following the remarkable reduction observed immediately after the fortification practice. There is accumulating evidence that folate receptor (FR) autoimmunity may play a role in the etiology of folate-sensitive NTDs. METHODS: From 2011 to 2013, 118 NTD cases and 242 healthy controls were recruited from a population-based birth defects surveillance system in Northern China. Enzyme-linked immunosorbent assay was used to measure FR autoantibodies in maternal and cord blood. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Plasma FR autoantibodies levels were significantly elevated in mothers of infants with NTDs compared with mothers of healthy controls. Using the lowest tertile as the referent group, 2.20-fold (95% CI, 0.71-6.80) and 5.53-fold increased odds (95% CI, 1.90-16.08) of NTDs were observed for the second and third tertile of immunoglobulin G (IgG), respectively, and the odds of NTDs for each successive tertile of IgM was 0.98 (95% CI, 0.35-2.75) and 3.49 (95% CI, 1.45-8.39), respectively. A dose-response relationship was found between FR autoantibodies levels and risk of NTDs (P < 0.001 for IgG, P = 0.002 for IgM). The same pattern was observed in both subtypes of spina bifida and anencephaly. No significant difference in levels of cord blood FR autoantibodies was observed. CONCLUSION: Higher levels of FR autoimmunity in maternal plasma are associated with elevated risk of NTDs in a dose-response manner. Birth Defects Research (Part A) 106:685-695, 2016. © 2016 Wiley Periodicals, Inc.
Subject(s)
Anencephaly/immunology , Autoantibodies/blood , Autoimmunity/drug effects , Folate Receptor 1/antagonists & inhibitors , Folic Acid/immunology , Immunoglobulin G/blood , Adult , Anencephaly/diagnosis , Anencephaly/genetics , Anencephaly/pathology , Case-Control Studies , China , Dose-Response Relationship, Immunologic , Drug Tolerance/immunology , Enzyme-Linked Immunosorbent Assay , Female , Folate Receptor 1/genetics , Folate Receptor 1/immunology , Folic Acid/administration & dosage , Gene Expression , Humans , Infant , Logistic Models , Male , Odds Ratio , RiskABSTRACT
Keratinous material, in the form of epithelial squames often with foreign body reaction and dense gliosis, was demonstrated in all of ten cases of anencephaly by a sensitive and specific immunohistochemical stain. In some cases keratin was not recognized on routine histological stains.
Subject(s)
Anencephaly/immunology , Foreign-Body Reaction/complications , Keratins/immunology , Anencephaly/complications , Anencephaly/pathology , Foreign-Body Reaction/pathology , Histocytochemistry , Humans , ImmunochemistryABSTRACT
An electroimmunodiffusion method on hydroxyethylcellulose-agarose by which IgA and IgM concentrations down to 0.3 mg/dl can be measured in amniotic fluid is presented. Elevated Ig levels were found in both fetal infection and in congenital malformations. The potential value of Ig determination in amniotic fluid is discussed.
Subject(s)
Amniotic Fluid/immunology , Counterimmunoelectrophoresis , Immunoelectrophoresis , Immunoglobulin A/analysis , Immunoglobulin M/analysis , Anencephaly/immunology , Female , Humans , Immunoglobulin G/analysis , Listeriosis/congenital , Listeriosis/immunology , Meningomyelocele/immunology , Pregnancy , Pregnancy Complications, Infectious/immunology , alpha-Fetoproteins/analysisABSTRACT
Geographical variation in the incidence of an Anencephaly and Spina-Bifida is well documented. The highest rates for these malformations were found in Ireland, Wales, Scotland and in Western regions of England. These rates decrease progressively towards eastern Europe. In France the highest rates were found in some regions of Brittany. The geographical correlations between the mortality rates of Spina-Bifida and incidence of Spina-Bifida and Anencephaly and the HLA antigen frequencies are studied. There is a positive correlation with A1 and B8 and a negative one with B5 and BW35. The role of the HLA system in these associations is discussed.
Subject(s)
Anencephaly/epidemiology , HLA Antigens/analysis , Spina Bifida Occulta/epidemiology , Anencephaly/immunology , Europe , Female , Humans , Infant, Newborn , Male , Racial Groups , Spina Bifida Occulta/immunology , United KingdomABSTRACT
The geographical correlation between the incidence of spina bifida and anencephaly and the HLA and ABO antigen frequencies are studied. There is a positive correlation between these malformations and A1 and B8, and a negative correlation with B5 and Bw35. The role of the HLA system itself, or of a human T-like locus, is discussed. This study provides evidence of a possible genetic background of susceptibility to these malformations.
Subject(s)
Anencephaly/epidemiology , HLA Antigens/genetics , Spina Bifida Occulta/epidemiology , ABO Blood-Group System , Anencephaly/immunology , Australia , Canada , Europe , Female , Humans , Israel , Japan , Male , Mexico , South Africa , Spina Bifida Occulta/immunology , United StatesSubject(s)
Anencephaly/physiopathology , Endocrine Glands/embryology , Anencephaly/embryology , Anencephaly/immunology , Biological Evolution , Calcitonin/biosynthesis , Cell Differentiation , Female , Humans , Hypothalamus/physiology , Islets of Langerhans/immunology , Islets of Langerhans/pathology , Pituitary Gland, Anterior/immunology , Pituitary Gland, Anterior/pathology , Pregnancy , Thyroid Gland/pathologyABSTRACT
A survey has been carried out of lymphoreticular aggregates in the lungs of 200 children, stillborns and dying within 15 days of birth and in a further 21 children with anencephalus, and controls. Lymphoreticular aggregates occur in response to amniotic infection and are found in the 'intrauterine infection syndrome'. They are not found in children showing early hyaline membranes. The time interval required for the production of lymphoreticular aggregates in the human child appears to be at lease 48 h and is probably 72 h before the production of well-formed aggregates and this probably applies to both the intrauterine and the postnatal state. There is a significant increase in the number of lungs showing lymphoreticular aggregates at birth in children in whom there is neurospinal dysraphism. In such children there is necrosis of nervous tissue into the amniotic cavity and it would seem likely that this material has been antigenic to the lung in utero.
