Isolated congenital heart block. long-term outcome of mothers and characterization of the immune response to ss-a/ro and to ss-b/la

Authors

  • Heikki Julkunen MD,

    Corresponding author
    1. Fourth Department of Medicine, the Department of Bacteriology and Immunology, the Departments I and II of Obstetrics and Gynecology, the Department of Ophthalmology, and Children's Hospital, Helsinki University Central Hospital, and United Laboratories, Helsinki, Finland; and the Scripps Research Institute, La Jolla, California.
    Current affiliation:
    1. Peijas-Rekola Hospital, Vantaa, Finland
    • Division of Rheumatology, Fourth Department of Medicine, Helsinki University Central Hospital, Unioninkatu 38, 00170 Helsinki, Finland
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  • Pekka Kurki MD,

    1. Fourth Department of Medicine, the Department of Bacteriology and Immunology, the Departments I and II of Obstetrics and Gynecology, the Department of Ophthalmology, and Children's Hospital, Helsinki University Central Hospital, and United Laboratories, Helsinki, Finland; and the Scripps Research Institute, La Jolla, California.
    Current affiliation:
    1. Department of Clinical Research, Sandoz, Helsinki, Finland
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  • Risto Kaaja MD,

    1. Fourth Department of Medicine, the Department of Bacteriology and Immunology, the Departments I and II of Obstetrics and Gynecology, the Department of Ophthalmology, and Children's Hospital, Helsinki University Central Hospital, and United Laboratories, Helsinki, Finland; and the Scripps Research Institute, La Jolla, California.
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  • Ritva Heikkilä MSc,

    1. Fourth Department of Medicine, the Department of Bacteriology and Immunology, the Departments I and II of Obstetrics and Gynecology, the Department of Ophthalmology, and Children's Hospital, Helsinki University Central Hospital, and United Laboratories, Helsinki, Finland; and the Scripps Research Institute, La Jolla, California.
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  • Ilkka Immonen MD,

    1. Fourth Department of Medicine, the Department of Bacteriology and Immunology, the Departments I and II of Obstetrics and Gynecology, the Department of Ophthalmology, and Children's Hospital, Helsinki University Central Hospital, and United Laboratories, Helsinki, Finland; and the Scripps Research Institute, La Jolla, California.
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  • Edward K. L. Chan PhD,

    1. Fourth Department of Medicine, the Department of Bacteriology and Immunology, the Departments I and II of Obstetrics and Gynecology, the Department of Ophthalmology, and Children's Hospital, Helsinki University Central Hospital, and United Laboratories, Helsinki, Finland; and the Scripps Research Institute, La Jolla, California.
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  • Eric Wallgren MD,

    1. Fourth Department of Medicine, the Department of Bacteriology and Immunology, the Departments I and II of Obstetrics and Gynecology, the Department of Ophthalmology, and Children's Hospital, Helsinki University Central Hospital, and United Laboratories, Helsinki, Finland; and the Scripps Research Institute, La Jolla, California.
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  • Claes Friman MD

    1. Fourth Department of Medicine, the Department of Bacteriology and Immunology, the Departments I and II of Obstetrics and Gynecology, the Department of Ophthalmology, and Children's Hospital, Helsinki University Central Hospital, and United Laboratories, Helsinki, Finland; and the Scripps Research Institute, La Jolla, California.
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Abstract

Objective. To study the long-term outcome of mothers of children with isolated congenital heart block (CHB) and to characterize the maternal autoantibody response to SS-A/Ro and SS-B/La.

Methods. A retrospective clinical study of 33 mothers a mean of 11.2 years (SD 9.2 years, range 0–32 years) after the delivery of their first child with CHB. A clinical and immunologic study of 31 of these mothers, compared with 89 healthy mothers, 45 mothers with systemic lupus erythematosus (SLE), and 19 mothers with primary Sjögren's syndrome (SS), all of whom had healthy children. The specificity of the autoantibody responses to SS-A/Ro and SS-B/La was studied by enzyme-linked immunosorbent assays using purified human recombinant antigens and affinity-purified antigens.

Results. By the time of the analysis, 2 (6%) of the 33 mothers of CHB children had died and 6 (18%) had met the criteria for SLE. As a group, mothers of CHB children had clinical and immunologic characteristics more closely related to primary SS than to SLE or any other connective tissue disease. The predominant autoantibody response was to the SS-A/Ro antigens, notably to the 52-kd SS-A/Ro protein (prevalence 97%). Compared with controls with SLE, mothers of CHB children had higher titers of antibodies to recombinant 52-kd and 60-kd SS-A/Ro proteins and to the affinity-purified SS-A/Ro antigen (P < 0.05, P < 0.01, and P < 0.001, respectively). Compared with controls with primary SS, the autoantibody responses were similar.

Conclusion. The predominant autoimmune disorder in mothers of children with CHB is subclinical primary SS. Antibodies to SS-A/Ro appear to be a prerequisite for the development of CHB.

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