Maternal serum IL-22 concentrations are significantly upregulated in patients with preterm premature rupture of membranes
Abstract
Objectives: This study aimed to compare the serum IL-22 levels between preterm premature rupture of membranes (PPROM) patients and the control group with intact membranes. We also hypothesized whether serum IL-22 upregulation might contribute to defense against inflammatory responses and improve the pregnancy outcomes.
Material and methods: We performed this prospective case-control study between 24–34 weeks of pregnancy. We enrolled 40 singleton pregnant patients with PPROM and 40 healthy gestational age- and gravidity-matched patients without PPROM. The degree of association between variables and IL-22 were calculated by Spearman correlation coefficients where appropriate. Scatter plots were given for statistically significant correlations. ROC curve was constructed to illustrate the sensitivity and specificity performance characteristics of IL-22, and a cutoff value was estimated by using the index of Youden.
Results: Maternal serum IL-22 levels were significantly higher in PPROM patients (60.34 ± 139.81 pg/mL) compared to the participants in the control group (20.71 ± 4.36 pg/mL, p < 0.001). When we analyze the area under the ROC curve (AUC), the IL-22 value can be considered a statistically significant parameter for diagnosing PPROM. According to the Youden index, a 23.86 pg/mL cut-off value of IL-22 can be used to diagnosing PPROM with 72% sensitivity and 61.5% specificity. There was no positive correlation between serum IL-22 levels and maternal C-reactive protein (CRP) value, procalcitonin value, latency period, birth week, birth weight, and umbilical cord blood pH value.
Conclusions: Maternal serum IL-22 levels were significantly higher in PPROM patients than healthy pregnant women with an intact membrane. We suggest that IL-22 might be a crucial biomarker of the inflammatory process in PPROM.
Keywords: preterm premature rupture of membranesinterleukin-22neonatal outcomes
References
- Modi BP, Parikh HI, Teves ME, et al. Discovery of rare ancestry-specific variants in the fetal genome that confer risk of preterm premature rupture of membranes (PPROM) and preterm birth. BMC Med Genet. 2018; 19(1): 181.
- Cobo T, Kacerovsky M, Palacio M, et al. Intra-amniotic inflammatory response in subgroups of women with preterm prelabor rupture of the membranes. PLoS One. 2012; 7(8): e43677.
- Mercer BM, Crouse DT, Goldenberg RL, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. The antibiotic treatment of PPROM study: systemic maternal and fetal markers and perinatal outcomes. Am J Obstet Gynecol. 2012; 206(2): 145.e1–145.e9.
- Gilman-Sachs A, Dambaeva S, Salazar Garcia MD, et al. Inflammation induced preterm labor and birth. J Reprod Immunol. 2018; 129: 53–58.
- Chang HH, Larson J, Blencowe H, et al. Born Too Soon preterm prevention analysis group. Preventing preterm births: analysis of trends and potential reductions with interventions in 39 countries with very high human development index. Lancet. 2013; 381(9862): 223–234.
- Baran ŞY, Törer B, Kalaycı H, et al. The Effect of the Cause of Delivery on Neonatal Outcomes in Early Preterm Deliveries. Journal of Fetal Medicine. 2019; 6(3): 139–145.
- Aghaeepour N, Ganio EA, Mcilwain D, et al. An immune clock of human pregnancy. Sci Immunol. 2017; 2(15).
- Oğlak SC, Aydın MF. Are neutrophil to lymphocyte ratio and platelet to lymphocyte ratio clinically useful for the prediction of early pregnancy loss? Ginekol Pol. 2020; 91(9): 524–527.
- Menon R, Richardson LS. Preterm prelabor rupture of the membranes: A disease of the fetal membranes. Semin Perinatol. 2017; 41(7): 409–419.
- Tita ATN, Andrews WW. Diagnosis and management of clinical chorioamnionitis. Clin Perinatol. 2010; 37(2): 339–354.
- Martinez-Portilla RJ, Hawkins-Villarreal A, Alvarez-Ponce P, et al. Maternal Serum Interleukin-6: A Non-Invasive Predictor of Histological Chorioamnionitis in Women with Preterm-Prelabor Rupture of Membranes. Fetal Diagn Ther. 2019; 45(3): 168–175.
- Bersani I, De Carolis MP, Foell D, et al. Interleukin-22: biomarker of maternal and fetal inflammation? Immunol Res. 2015; 61(1-2): 4–10.
- Witte E, Witte K, Warszawska K, et al. Interleukin-22: a cytokine produced by T, NK and NKT cell subsets, with importance in the innate immune defense and tissue protection. Cytokine Growth Factor Rev. 2010; 21(5): 365–379.
- Dudakov JA, Hanash AM, van den Brink MRM. Interleukin-22: immunobiology and pathology. Annu Rev Immunol. 2015; 33: 747–785.
- Dambaeva S, Schneiderman S, Jaiswal MK, et al. Interleukin 22 prevents lipopolysaccharide- induced preterm labor in mice. Biol Reprod. 2018; 98(3): 299–308.
- Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 188: Prelabor Rupture of Membranes. Obstet Gynecol. 2018; 131(1): e1–e14.
- Abdelazim IA, Makhlouf HH. Placental alpha microglobulin-1 (AmniSure(®) test) for detection of premature rupture of fetal membranes. Arch Gynecol Obstet. 2012; 285(4): 985–989.
- Asadi N, Faraji A, Keshavarzi A, et al. Predictive value of procalcitonin, C-reactive protein, and white blood cells for chorioamnionitis among women with preterm premature rupture of membranes. Int J Gynaecol Obstet. 2019; 147(1): 83–88.
- Oğlak SC, Bademkıran MH, Obut M. Predictor variables in the success of slow-release dinoprostone used for cervical ripening in intrauterine growth restriction pregnancies. J Gynecol Obstet Hum Reprod. 2020; 49(6): 101739.
- ACOG Practice Bulletin No. 106: Intrapartum fetal heart rate monitoring: nomenclature, interpretation, and general management principles. Obstet Gynecol. 2009; 114(1): 192–202.
- Obut M, Oğlak SC. Expression of CD44 and IL-10 in normotensive and preeclamptic placental tissue. Ginekol Pol. 2020; 91(6): 334–341.
- Oglak S, Obut M. Expression of ADAMTS13 and PCNA in the Placentas of Gestational Diabetic Mothers. International Journal of Morphology. 2021; 39(1): 38–44.
- Behram M, Oğlak SC, Doğan Y. Evaluation of BRD4 levels in patients with early-onset preeclampsia. J Gynecol Obstet Hum Reprod. 2021; 50(2): 101963.
- Eyerich K, Dimartino V, Cavani A. IL-17 and IL-22 in immunity: Driving protection and pathology. Eur J Immunol. 2017; 47(4): 607–614.
- Mühl H, Scheiermann P, Bachmann M, et al. IL-22 in tissue-protective therapy. Br J Pharmacol. 2013; 169(4): 761–771.
- Eyerich S, Eyerich K, Pennino D, et al. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest. 2009; 119(12): 3573–3585.
- Wang Y, Xu B, Li MQ, et al. IL-22 secreted by decidual stromal cells and NK cells promotes the survival of human trophoblasts. Int J Clin Exp Pathol. 2013; 6(9): 1781–1790.
- Xu Yi, Romero R, Miller D, et al. Innate lymphoid cells at the human maternal-fetal interface in spontaneous preterm labor. Am J Reprod Immunol. 2018; 79(6): e12820.
- Aris IM, Logan S, Lim C, et al. Preterm prelabour rupture of membranes: a retrospective cohort study of association with adverse outcome in subsequent pregnancy. BJOG. 2017; 124(11): 1698–1707.
- Sorokin Y, Romero R, Mele L, et al. Maternal serum interleukin-6, C-reactive protein, and matrix metalloproteinase-9 concentrations as risk factors for preterm birth <32 weeks and adverse neonatal outcomes. Am J Perinatol. 2010; 27(8): 631–640.