Lymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features in systemic lupus erythematosus (SLE). We speculate whether lymphocyte subset counts are affected by pregnancy and if they relate to autoantibody profiles and/or IFNα protein in SLE pregnancy. Repeated blood samples were collected during pregnancy from 80 women with SLE and 51 healthy controls (HC). Late postpartum samples were obtained from 19 of the women with SLE. Counts of CD4 + and CD8 + T cells, B cells and NK cells were measured by flow cytometry. Positivity for anti-nuclear antibodies (ANA) fine specificities (double-stranded DNA [dsDNA], Smith [Sm], ribonucleoprotein [RNP], chromatin, Sjögren’s syndrome antigen A [SSA] and B [SSB]) and anti-phospholipid antibodies (cardiolipin [CL] and β2 glycoprotein I [β2GPI]) was assessed with multiplexed bead assay. IFNα protein concentration was quantified with Single molecule array (Simoa) immune assay. Clinical data were retrieved from medical records. Women with SLE had lower counts of all lymphocyte subsets compared to HC throughout pregnancy, but counts did not differ during pregnancy compared to postpartum. Principal component analysis revealed that low lymphocyte subset counts differentially related to autoantibody profiles, cluster one (anti-dsDNA/anti-Sm/anti-RNP/anti-Sm/RNP/anti-chromatin), cluster two (anti-SSA/anti-SSB) and cluster three (anti-CL/anti-β2GPI), IFNα protein levels and disease activity. CD4 + T cell counts were lower in women positive to all ANA fine specificities in cluster one compared to those who were negative, and B cell numbers were lower in women positive for anti-dsDNA and anti-Sm compared to negative women. Moreover, CD4 + T cell and B cell counts were lower in women with moderate/high compared to no/low disease activity, and CD4 + T cell count was lower in IFNα protein positive relative to negative women. Finally, CD4 + T cell count was unrelated to treatment. Lymphocyte subset counts are lower in SLE compared to healthy pregnancies, which seems to be a feature of the disease per se and not affected by pregnancy. Our results also indicate that low lymphocyte subset counts relate differentially to autoantibody profiles, IFNα protein levels and disease activity, which could be due to divergent disease pathways.

中文翻译：

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系统性红斑狼疮妊娠期 CD4+T 细胞计数低与特异性抗核抗体、IFNα 蛋白阳性和疾病活动性相关

淋巴细胞减少、自身抗体和 I 型干扰素 (IFN) 系统激活是系统性红斑狼疮 (SLE) 的常见特征。我们推测淋巴细胞亚群计数是否受妊娠影响，以及它们是否与 SLE 妊娠中的自身抗体谱和/或 IFNα 蛋白相关。在怀孕期间从 80 名 SLE 女性和 51 名健康对照 (HC) 中重复采集血液样本。从 19 名患有系统性红斑狼疮的女性身上获取了产后晚期样本。通过流式细胞术测量CD4+和CD8+T细胞、B细胞和NK细胞的计数。抗核抗体 (ANA) 精细特异性（双链 DNA [dsDNA]、Smith [Sm]、核糖核蛋白 [RNP]、染色质、干燥综合征抗原 A [SSA] 和 B [SSB]）和抗磷脂抗体呈阳性（心磷脂 [CL] 和 β2 糖蛋白 I [β2GPI]）通过多重微珠测定进行评估。使用单分子阵列 (Simoa) 免疫测定对 IFNα 蛋白浓度进行定量。从医疗记录中检索临床数据。与正常人相比，患有系统性红斑狼疮的女性在整个怀孕期间的所有淋巴细胞亚群计数均较低，但与产后相比，怀孕期间的计数没有差异。主成分分析显示，低淋巴细胞亚群计数与自身抗体谱存在差异相关，簇一（抗 dsDNA/抗 Sm/抗 RNP/抗 Sm/RNP/抗染色质），簇二（抗 SSA/抗-染色质） SSB）和簇三（抗 CL/抗 β2GPI）、IFNα 蛋白水平和疾病活动。与阴性女性相比，第一簇中所有 ANA 精细特异性呈阳性的女性的 CD4 + T 细胞计数较低，与阴性女性相比，抗 dsDNA 和抗 Sm 阳性的女性的 B 细胞数量较低。此外，与无/低疾病活动性女性相比，中/高疾病活动性女性的 CD4 + T 细胞和 B 细胞计数较低，并且相对于阴性女性，IFNα 蛋白阳性的女性 CD4 + T 细胞计数较低。最后，CD4+T细胞计数与治疗无关。与健康妊娠相比，系统性红斑狼疮患者的淋巴细胞亚群计数较低，这似乎是该疾病本身的一个特征，并且不受妊娠的影响。我们的结果还表明，低淋巴细胞亚群计数与自身抗体谱、IFNα 蛋白水平和疾病活动性存在不同的相关性，这可能是由于不同的疾病途径所致。