Cardiac expression of 52beta, 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, 52beta (MW 45 kd), recognized by CHB maternal antisera. This study was designed to identify whether cardiac expression of 52beta and full-length 52alpha 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 52beta was greatest and 52alpha lowest between 14 and 16 weeks of gestation. In fetal hearts ages 22-25 weeks and adult heart, the 52beta transcript was markedly diminished and 52alpha clearly dominated. The 52beta mRNA was observed in a 15-week brain, kidney, lung, and spleen; however, its expression relative to 52alpha was greatest in the heart.


CONCLUSIONS
Since expression of the alternative product 52beta 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 52beta in the development of CHB is implicated. Although other fetal tissues express 52beta, there may be differences in accessibility of antigen or regenerative capacities.
Buyon
J P
JP
New York University School of Medicine and Hospital for Joint Diseases, New York, NY 10003, USA.
Tseng
C E
CE
Di Donato
F
F
Rashbaum
W
W
Morris
A
A
Chan
E K
EK
D000328:Adult; D017398:Alternative Splicing; D001324:Autoantigens / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D005318:Fetal Heart / Q000378:metabolism*; D005865:Gestational Age; D006327:Heart Block / Q000151:congenital* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins / Q000096:biosynthesis* / Q000235:genetics; D000099207:SS-A Antigen
D001324:Autoantigens; D017931:DNA Primers; D012333:RNA, Messenger; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C116006:RO60 protein, human