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

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...

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Published in:Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2011-09, Vol.63 (9), p.2783-2789
Main Authors: Routsias, John G., Kyriakidis, Nikolaos C., Friedman, Deborah M., Llanos, Carolina, Clancy, Robert, Moutsopoulos, Haralampos M., Buyon, Jill, Tzioufas, Athanasios G.
Format: Article
Language:English
Subjects:
Antibodies, Anti-Idiotypic - immunology
Antibody response
Autoantibodies
Autoimmune Diseases - drug therapy
Autoimmune Diseases - immunology
Autoimmune Diseases - prevention & control
Biological and medical sciences
Birth
Cardiac dysrhythmias
Cardiology. Vascular system
congenital heart block
Diseases of the osteoarticular system
Epitopes
Exanthema
Female
Heart
Heart Block - congenital
Heart Block - drug therapy
Heart Block - immunology
Heart Block - prevention & control
Humans
Idiotypes
Immunoglobulin Idiotypes - immunology
Immunoglobulins
Immunoglobulins, Intravenous - immunology
Immunoglobulins, Intravenous - therapeutic use
Intravenous administration
Lupus
Lymphocytes B
Medical research
Medical sciences
Neonates
Pregnancy
Progeny
Prospective Studies
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Summary: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
ISSN:0004-3591
2326-5191
1529-0131
1529-0131
2326-5205
DOI:10.1002/art.30464