Children's Hospital Oakland Research Institute, Oakland, CA, USA.
Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Arthritis Res Ther. 2023 Oct 4;25(1):191. doi: 10.1186/s13075-023-03169-6.
While many women with rheumatoid arthritis (RA) improve during pregnancy and others worsen, there are no biomarkers to predict this improvement or worsening. In our unique RA pregnancy cohort that includes a pre-pregnancy baseline, we have examined pre-pregnancy gene co-expression networks to identify differences between women with RA who subsequently improve during pregnancy and those who worsen.
Blood samples were collected before pregnancy (T0) from 19 women with RA and 13 healthy women enrolled in our prospective pregnancy cohort. RA improvement/worsening between T0 and 3rd trimester was assessed by changes in the Clinical Disease Activity Index (CDAI). Pre-pregnancy expression profiles were examined by RNA sequencing and differential gene expression analysis. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules correlated with the improvement/worsening of RA during pregnancy and to assess their functional relevance.
Of the 19 women with RA, 14 improved during pregnancy (RA) while 5 worsened (RA). At the T0 baseline, however, the mean CDAI was similar between the two groups. WGCNA identified one co-expression module related to B cell function that was significantly correlated with the worsening of RA during pregnancy and was significantly enriched in genes differentially expressed between the RA and RA groups. A neutrophil-related expression signature was also identified in the RA group at the T0 baseline.
The pre-pregnancy gene expression signatures identified represent potential biomarkers to predict the subsequent improvement/worsening of RA during pregnancy, which has important implications for the personalized treatment of RA during pregnancy.
虽然许多患有类风湿关节炎 (RA) 的女性在怀孕期间会有所改善，而其他女性则会恶化，但目前尚无生物标志物可预测这种改善或恶化。在我们独特的 RA 妊娠队列中，包括妊娠前基线，我们已经检查了妊娠前基因共表达网络，以确定在怀孕期间随后改善和恶化的 RA 女性之间的差异。
从我们前瞻性妊娠队列中招募的 19 名患有 RA 的女性和 13 名健康女性在妊娠前 (T0) 采集血液样本。通过临床疾病活动指数 (CDAI) 的变化评估 T0 和第 3 孕期之间的 RA 改善/恶化。通过 RNA 测序和差异基因表达分析检查妊娠前表达谱。使用加权基因共表达网络分析 (WGCNA) 来识别与妊娠期间 RA 改善/恶化相关的共表达模块，并评估其功能相关性。
在 19 名患有 RA 的女性中，有 14 名在怀孕期间病情改善 (RA)，而 5 名病情恶化 (RA)。然而，在 T0 基线时，两组的平均 CDAI 相似。WGCNA 确定了一个与 B 细胞功能相关的共表达模块，该模块与妊娠期间 RA 的恶化显著相关，并且在 RA 和 RA 组之间差异表达的基因中显著富集。在 RA 组中还在 T0 基线时鉴定出一个与中性粒细胞相关的表达特征。
鉴定的妊娠前基因表达特征代表了预测妊娠期间 RA 随后改善/恶化的潜在生物标志物，这对 RA 妊娠期间的个性化治疗具有重要意义。
