Association of the idiotype:antiidiotype antibody ratio with the efficacy of intravenous immunoglobulin treatment for the prevention of recurrent autoimmune-associated congenital heart block.

Abstract

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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 (P<0.0001). 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 of <1, 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.

CONCLUSION:

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.

• Authors: John G Routsias, Nikolaos C Kyriakidis, Deborah M Friedman, Carolina Llanos, Robert Clancy, Haralampos M Moutsopoulos, Jill Buyon, Athanasios G Tzioufas
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 63 Issue 9 Pg. 2783-9 (Sep 2011) ISSN: 1529-0131 [Electronic] United States
• PMID: 21618202 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 by the American College of Rheumatology.

Chemical References

• Antibodies, Anti-Idiotypic
• Immunoglobulin Idiotypes
• Immunoglobulins, Intravenous

Topics

• Antibodies, Anti-Idiotypic (immunology)
• Autoimmune Diseases (drug therapy, immunology, prevention & control)
• Female
• Heart Block (congenital, drug therapy, immunology, prevention & control)
• Humans
• Immunoglobulin Idiotypes (immunology)
• Immunoglobulins, Intravenous (immunology, therapeutic use)
• Pregnancy
• Prospective Studies