Cardiac expression of 52β, an alternative transcript of the congenital heart block-associated 52-kd SS-A/Ro autoantigen, is maximal during fetal development

Objective. Congenital heart block (CHB), associated with antibodies to SS-A/Ro and SS-B/La, is most often detected between 18 and 24 weeks of gestation, yet the maternal heart is unaffected. We recently described an alternatively spliced 52-kd SS-A/Ro messenger RNA (mRNA) derived from the skipping of exon 4 which encodes a smaller protein, 52β (MW 45 kd), recognized by CHB maternal antisera. This study was designed to identify whether cardiac expression of 52β and fulllength 52α relates to the development of CHB.

Methods. Reverse transcriptase-polymerase chain reaction was performed using primers flanking exon 4 and mRNA from 22 human fetal hearts (age 11–25 weeks) and 3 adult hearts. The brain, kidney, liver, lung, and spleen were similarly evaluated in a 15-week, an 18-week, and a 24-week fetus.

Results. Expression of 52β was greatest and 52α lowest between 14 and 16 weeks of gestation. In fetal hearts ages 22–25 weeks and adult heart, the 52β transcript was markedly diminished and 52α clearly dominated. The 52β mRNA was observed in a 15-week brain, kidney, lung, and spleen; however, its expression relative to 52α was greatest in the heart.

Conclusion. Since expression of the alternative product 52β is maximal at the time of cardiac ontogeny when maternal antibodies gain access to the fetal circulation, just prior to the clinical detection of bradyarrhythmia, a role for 52β in the development of CHB is implicated. Although other fetal tissues express 52β, there may be differences in accessibility of antigen or regenerative capacities.