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Autoimmune Response in Mothers of Children with Congenital and Postnatally Diagnosed Isolated Heart Block: A Population Based Study
HEIKKI JULKUNEN, AARO MIETTINEN, TIMO K. WALLE, EDWARD K.L. CHAN, and MARIANNE ERONEN
ABSTRACT.
Methods. We reviewed the Finnish hospital registries for patients born between 1950 and 2000 and diagnosed with isolated HB before the age of 16 years. Clinical data and sera for the determination of autoantibodies were available from 67 mothers of children with CHB and from 37 mothers of children with postnatally diagnosed HB 9.9 years and 22.6 years (mean) after the index delivery, respectively. Maternal antibodies to 52 kDa and 60 kDa SSA and 48 kDa SSB were determined by time-resolved fluoroimmunoassay (TR-FIA) and by immunoblotting. Other marker antibodies for connective tissue diseases (CTD) were determined by immunoblot and/or by immunofluorescence. The control group comprised 136 mothers with primary Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), or other CTD with healthy children. Results. Sixty of our 67 mothers (90%) of children with CHB had antibodies to SSA or SSB by the methods initially used in this study. When retests and tests performed previously were taken into account, only 3 (4%) of the 67 mothers did not have any autoantibodies. Two (3%) of the 67 mothers had antibodies to dsDNA and one (1%) each to Jo-1/HRS, RNP-70 kDa, and histone proteins. Of 37 mothers of children with postnatally diagnosed HB, only 3 (8%) had any autoantibodies. Increased risk of having a child with CHB was indicated by maternal primary SS and high levels of anti-SSA and anti-SSB by all assays, whereas low risk was indicated by maternal SLE or other CTD and undetectable or low levels of the antibodies. No single anti-SSA or anti-SSB test was clearly superior to others, but in general, immunoblots were more specific than TR-FIA. Conclusion. Maternal autoimmune disorder is almost always associated with CHB but only rarely with postnatally diagnosed HB. Anti-SSA and anti-SSB are marker antibodies for mothers of children with CHB, and an increased risk of having an affected child is indicated by maternal primary SS and high titer antibodies to SSA and SSB. (J Rheumatol 2004;31:183-9) Key Indexing Terms:
NEONATAL LUPUS
From the Department of Internal Medicine, Peijas Hospital, Helsinki University Hospital, Vantaa; the Department of Immunology, HUCH Laboratory Diagnostics, Helsinki University Hospital; the Hospital for Children and Adolescents, Helsinki University Hospital, Helsinki, Finland; and the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA. Supported in part by Helsinki University Hospital Research Foundation, the Sigrid Juselius Foundation, Finska Läkarsällskapet, and Helsinki University Hospital. H. Julkunen, MD, Rheumatologist, Department of Internal Medicine, Peijas Hospital; A. Miettinen, MD, Clinical Immunologist; T.K. Walle, MD, Clinical Immunologist, Department of Immunology, HUCH Laboratory Diagnostics; E.K.L. Chan, PhD, Department of Molecular and Experimental Medicine, The Scripps Research Institute; M. Eronen, MD, Pediatric Cardiologist, Hospital for Children and Adolescents, Helsinki University Hospital. Address reprint requests to Dr. H. Julkunen, Department of Internal Medicine, Peijas Hospital, Helsinki University Hospital, 01400 Vantaa, Finland. E-mail: heikki.julkunen@hus.fi Submitted October 11, 2002; revision accepted July 24, 2003. |