Increased frequency of complement C4 ‘null’ alleles in recurrent spontaneous abortions

Abstract

Typings for major histocompatibility antigens HLA A, B, C and DR and for complement C4A, C4B and factor B were performed for 59 Finnish couples experiencing at least three consecutive recurrent spontaneous abortions (RSA). Forty-one of them were primary abortion (PA) couples with no children and 18 were secondary abortion (SA) couples who had one or two children before abortions. HLA sharing in A and B loci was slightly but significantly increased (15%, P less than 0.05) among RSA couples compared to the controls, as was DR sharing among SA couples compared to PA couples (50% versus 22%, P less than or equal to 0.05). The most interesting new finding, however, was the statistically significant increase of complement C4 functionally silent, i.e. C4 'null', alleles in RSA couples. C4 is a duplicated gene and its products differ in their functions in the complement cascade. C4A null alleles were equally increased in PA wives and in PA husbands (32%, P less than or equal to 0.05) compared to the controls (18%) and C4B null alleles in SA wives (56%, P less than or equal to 0.05) and in SA husbands (50%) compared to the controls (29%). Therefore, the offspring of RSA couples have a significantly increased risk of inheriting several null alleles. The majority, 95% (P less than 0.001) of PA couples and 83% of SA couples, had at least one C4A or C4B null in their phenotypes compared to 66% among Finnish controls.