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Complete congenital heart block is associated with increased autoantibody titers against calreticulin
T Orth1, T Dorner, K H Meyer Zum Buschenfelde
1I. Medizinische Klinik und Poliklinik der Johannes Gutenberg-University of Mainz, Germany.
Insights
Anti-calreticulin autoantibodies were detected in infants with complete congenital heart block (CCHB). This suggests a potential role for calreticulin in CCHB pathogenesis, possibly as a passively acquired autoimmune condition.
Area of Science:
- Immunology
- Cardiology
- Reproductive Medicine
Background:
- Complete congenital heart block (CCHB) is linked to maternal anti-Ro/SS-A and anti-La/SS-B antibodies.
- Calreticulin, an endoplasmic reticulum protein, is distinct from the Ro/SS-A ribonucleoprotein complex.
- The role of anti-calreticulin autoantibodies in CCHB is not well understood.
Purpose of the Study:
- To investigate the presence and significance of anti-calreticulin autoantibodies in infants with CCHB and their mothers.
- To compare anti-calreticulin antibody responses in CCHB cases versus a control group of infants with anti-Ro/SS-A or anti-La/SS-B antibodies but without heart block.
- To explore the potential contribution of calreticulin to the autoimmune mechanisms underlying CCHB.
Main Methods:
- Serum samples from 18 infants with CCHB, their mothers, and 11 control infants (with anti-Ro/SS-A or anti-La/SS-B but no CCHB) and their mothers were analyzed.
- Specific enzyme-linked immunosorbent assays (ELISAs) were employed to detect IgG and IgM anti-calreticulin autoantibodies.
- Antibody responses were compared between the CCHB group, the control group, and healthy infant controls.
Main Results:
- Nine out of 18 infants with CCHB tested positive for IgG anti-calreticulin antibodies.
- Four of these also had IgM anti-calreticulin antibodies; one infant had IgM antibodies only.
- The non-CCHB control group showed lower positivity rates (two IgG, one IgM), and healthy infants were negative.
Conclusions:
- The presence of anti-calreticulin autoantibodies, including IgM, in CCHB infants suggests a potential role in the condition's development.
- Observed differences in antibody responses between infants and mothers support a hypothesis of fetal-mediated, passively acquired autoimmune disease.
- Calreticulin's function in calcium storage may be relevant to how anti-calreticulin antibodies influence CCHB development.
Abstract:
Complete congenital heart block (CCHB) is associated with anti-Ro/SS-A and anti-La/SS-B antibodies. Calreticulin, a calcium-binding, multi-functional protein of the endoplasmic reticulum with C-terminal KDEL-sequence, is not part of the Ro/SS-A ribonucleoprotein complex. In this study anti-calreticulin autoantibody responses in serum samples from 18 infants with CCHB, their mothers and in a control group of 11 anti-Ro/SS-A or anti-La/SS-B positive infants without heart block and their mothers were analysed. Specific enzyme-linked immunosorbent assays were performed. Nine out of 18 sera with CCHB contained IgG anti-calreticulin antibodies. Four sera of those with IgG antibodies also had IgM antibodies. One serum contained anti-calreticulin IgM antibodies only. In the non-CCHB group two sera were positive for IgG and one serum was positive for IgM anti-calreticulin antibodies. Sera of healthy infants were negative both for anti-IgG and anti-IgM calreticulin antibodies. Calreticulin is involved in calcium storage and therefore anti-calreticulin antibodies might influence the development of CCHB. The new finding of IgM autoantibodies and the observed differences in antibody response in infants and mothers support the hypothesis of a fetally mediated and passively acquired autoimmune disease.