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Association of the idiotype:antiidiotype antibody ratio with the efficacy of intravenous immunoglobulin treatment for the prevention of recurrent autoimmune-associated congenital heart block
- Source :
- ARTHRITIS AND RHEUMATISM, Artículos CONICYT, CONICYT Chile, instacron:CONICYT
- Publication Year :
- 2011
-
Abstract
- Congenital heart block (CHB), a manifestation of neonatal lupus, is associated with maternal anti-Ro/SSA and anti-La/SSB autoantibodies and recurs in ∼18% of subsequent pregnancies. This study was undertaken to investigate the effect of the idiotype:antiidiotype (Id:anti-Id) antibody ratio in the ability of intravenous immunoglobulin (IVIG) administered during subsequent pregnancies to prevent CHB.We studied 16 anti-Ro/SSA and anti-La/SSB-positive pregnant women from the Preventive IVIG Therapy for Congenital Heart Block study who had previously given birth to a child with neonatal lupus. In 3 of the mothers, the study pregnancy resulted in the birth of a child with neonatal lupus (2 with CHB and 1 with rash). Sequential serum samples were obtained from all mothers immediately before the administration of IVIG during pregnancy and were evaluated for antibodies against the major B cell epitope 349-364aa of La/SSB (idiotype) and its antiidiotypic antibodies.Following IVIG treatment, serum titers of anti-La(349-364) (Id antibodies) decreased in 80% of the mothers, and in 60% an increase in anti-Id antibodies against anti-La(349-364) was observed. The Id:anti-Id ratio was significantly higher in mothers whose offspring developed neonatal lupus compared to mothers who gave birth to a healthy child (P0.0001). Removal of anti-Id antibodies substantially increased the reactivity against La(349-364) in sera from 5 of 7 mothers tested. All IVIG preparations were examined for Id and anti-Id antibody activity. IVIG from batches administered to mothers who gave birth to a healthy child had an Id:anti-Id activity ratio of1, in contrast to that given to mothers who gave birth to a child with neonatal lupus. Addition of the IVIG preparations to the maternal sera further enhanced antiidiotypic activity (by up to 4.7-fold) in 11 of 13 patients studied.This is the first study in humans to demonstrate that IVIG influences the Id-anti-Id network of a specific pathogenic autoantibody. Specifically, we showed that IVIG enhanced the anti-Id antibody response in pregnant women with anti-La/SSB antibodies. A high Id:anti-Id ratio in both the IVIG preparation and the maternal serum may explain the absence of an effect of IVIG in preventing recurrent neonatal lupus in some cases.
- Subjects :
- Antiidiotype antibody
Idiotype
Heart block
Immunology
Article
Autoimmune Diseases
Rheumatology
Immunoglobulin Idiotypes
Pregnancy
medicine
Immunology and Allergy
Humans
Pharmacology (medical)
Prospective Studies
Prospective cohort study
biology
business.industry
Autoantibody
Immunoglobulins, Intravenous
medicine.disease
Antibodies, Anti-Idiotypic
Heart Block
biology.protein
Female
Antibody
business
Subjects
Details
- ISSN :
- 15290131
- Volume :
- 63
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Arthritis and rheumatism
- Accession number :
- edsair.doi.dedup.....821f1acb7f7b163631b715c3b664f704