Increased risk of rheumatoid arthritis among mothers with children who carryDRB1risk-associated alleles

Abstract

Findings support the hypothesis that a child's genotype can contribute independently to risk of RA among mothers.

Forward and reverse inheritance — the yin and the yang

“…The sequence DERAA, encoded at the same amino acid positions as the shared epitope but by other HLA‑DRB1 alleles, is considered to be RA-protective in most studies. As discussed by Cruz et al 1 , a previous study in patients with RA showed a deficit of non-inherited maternal alleles encoding DERAA compared with non-inherited paternal alleles. In light of this evidence, the finding of an increased risk of RA among women with a child who had a DERAA- encoding allele was unexpected 1 .…”

“…As discussed by Cruz et al 1 , a previous study in patients with RA showed a deficit of non-inherited maternal alleles encoding DERAA compared with non-inherited paternal alleles. In light of this evidence, the finding of an increased risk of RA among women with a child who had a DERAA- encoding allele was unexpected 1 . Although the explanation for this finding is unknown, one consideration is that the effect of maternal cells acquired during fetal life (when the immune system is developing) can be expected to differ from that of fetal cells acquired by an adult woman (when the immune system is mature).…”

“…A 2017 study by Cruz et al 1 reveals that the risk of a woman developing RA is influenced by the specific HLA alleles carried by any children born to her before disease onset. HLA molecules have a central role in the immune system, presenting foreign antigens and self-antigens as part of a network that, during health, is tolerant to normal self-antigens.…”

“…These sequence motifs are known as the ‘shared epitope’. Overall, Cruz et al 1 found that the risk of developing RA was increased among women who had given birth to a child with an allele encoding the shared epitope (adjusted for the mother’s status as a carrier of RA-risk alleles; OR 3.0, 95% CI 2.0–4.6).…”

“…When Cruz et al 1 stratified patients according to their shared epitope status, shared epitope-positive mothers with RA were more likely to have had a shared epitope-positive child than matched healthy women. Surprisingly, the corresponding results were not statistically significant for shared epitope-negative mothers, although the number of shared epitope-negative mothers among cases was low (31 shared epitope-negative cases among the 170 total cases).…”