Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) in the prediction of poor pregnancy outcomes in systemic lupus erythematosus (SLE)
Background Complement activation has been associated with adverse pregnancy outcomes (APO) in SLE. Pregnant women with SLE were studied to evaluate whether complement dysregulation within the first two pregnancy trimesters predicts APO.Methods Pregnant women fulfilled classification criteria for SLE...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2022-09-01
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| Series: | Lupus Science and Medicine |
| Online Access: | https://lupus.bmj.com/content/9/1/e000754.full |
| _version_ | 1811210776130617344 |
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| author | John Conklin Thierry Dervieux Peter Izmirly H Michael Belmont Jill P Buyon Roberta Vezza Alexander Michael Golpanian Alexis Engel |
| author_facet | John Conklin Thierry Dervieux Peter Izmirly H Michael Belmont Jill P Buyon Roberta Vezza Alexander Michael Golpanian Alexis Engel |
| author_sort | John Conklin |
| collection | DOAJ |
| description | Background Complement activation has been associated with adverse pregnancy outcomes (APO) in SLE. Pregnant women with SLE were studied to evaluate whether complement dysregulation within the first two pregnancy trimesters predicts APO.Methods Pregnant women fulfilled classification criteria for SLE. APO included neonatal death, preterm delivery before 36 weeks and small for gestational age newborn. Pre-eclampsia was also evaluated. Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) were measured by flow cytometry. Complement proteins C3 and C4 were measured by immunoturbidimetry and anti-double-stranded DNA by ELISA in serum. Statistical analysis consisted of t-test, confusion matrix-derived diagnostic analysis, and multivariate logistic regression.Results Fifty-one women had 57 pregnancies and 169 visits during the study. Baseline visits occurred mainly in the first (n=32) and second trimester (n=21). Fourteen (24.6%) pregnancies resulted in 21 APO with preterm delivery being the most common (n=10). ECR1 <5.5 net mean fluorescence intensity in the first trimester predicted APO with a diagnostic OR (DOR) of 18.33 (95% CI: 2.39 to 140.4; t-test p=0.04). Other individual biomarkers did not reach statistical significance. To estimate the likelihood of APO, we developed an algorithm that included the week of pregnancy, ECR1 and EC4d. From this algorithm, a Pregnancy Adversity Index (PAI) was calculated, and a PAI >0 indicated an elevated likelihood of pregnancy complications (DOR: 20.0 (95% CI: 3.64 to 109.97)).Conclusions Low levels of ECR1 in early or mid-pregnancy are predictive of an APO. Incorporating the weeks of gestation and both ECR1 and EC4d generated a PAI, which further predicted serious pregnancy complications. |
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| id | doaj.art-6348c5b9f5b6446fb4426df1493bb5d7 |
| institution | Directory Open Access Journal |
| issn | 2053-8790 |
| language | English |
| last_indexed | 2024-04-12T05:01:19Z |
| publishDate | 2022-09-01 |
| publisher | BMJ Publishing Group |
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| series | Lupus Science and Medicine |
| spelling | doaj.art-6348c5b9f5b6446fb4426df1493bb5d72022-12-22T03:46:59ZengBMJ Publishing GroupLupus Science and Medicine2053-87902022-09-019110.1136/lupus-2022-000754Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) in the prediction of poor pregnancy outcomes in systemic lupus erythematosus (SLE)John Conklin0Thierry Dervieux1Peter Izmirly2H Michael Belmont3Jill P Buyon4Roberta Vezza Alexander5Michael Golpanian6Alexis Engel7Exagen Inc, Vista, California, USAExagen Inc, Vista, California, USA1 Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USADivision of Rheumatology, New York University Grossman School of Medicine, New York, NY, USADivision of Rheumatology, New York University Grossman School of Medicine, New York, NY, USAExagen Inc, Vista, California, USADivision of Rheumatology, Department of Medicine, New York University School of Medicine, New York City, New York, USADivision of Rheumatology, Department of Medicine, New York University School of Medicine, New York City, New York, USABackground Complement activation has been associated with adverse pregnancy outcomes (APO) in SLE. Pregnant women with SLE were studied to evaluate whether complement dysregulation within the first two pregnancy trimesters predicts APO.Methods Pregnant women fulfilled classification criteria for SLE. APO included neonatal death, preterm delivery before 36 weeks and small for gestational age newborn. Pre-eclampsia was also evaluated. Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) were measured by flow cytometry. Complement proteins C3 and C4 were measured by immunoturbidimetry and anti-double-stranded DNA by ELISA in serum. Statistical analysis consisted of t-test, confusion matrix-derived diagnostic analysis, and multivariate logistic regression.Results Fifty-one women had 57 pregnancies and 169 visits during the study. Baseline visits occurred mainly in the first (n=32) and second trimester (n=21). Fourteen (24.6%) pregnancies resulted in 21 APO with preterm delivery being the most common (n=10). ECR1 <5.5 net mean fluorescence intensity in the first trimester predicted APO with a diagnostic OR (DOR) of 18.33 (95% CI: 2.39 to 140.4; t-test p=0.04). Other individual biomarkers did not reach statistical significance. To estimate the likelihood of APO, we developed an algorithm that included the week of pregnancy, ECR1 and EC4d. From this algorithm, a Pregnancy Adversity Index (PAI) was calculated, and a PAI >0 indicated an elevated likelihood of pregnancy complications (DOR: 20.0 (95% CI: 3.64 to 109.97)).Conclusions Low levels of ECR1 in early or mid-pregnancy are predictive of an APO. Incorporating the weeks of gestation and both ECR1 and EC4d generated a PAI, which further predicted serious pregnancy complications.https://lupus.bmj.com/content/9/1/e000754.full |
| spellingShingle | John Conklin Thierry Dervieux Peter Izmirly H Michael Belmont Jill P Buyon Roberta Vezza Alexander Michael Golpanian Alexis Engel Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) in the prediction of poor pregnancy outcomes in systemic lupus erythematosus (SLE) Lupus Science and Medicine |
| title | Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) in the prediction of poor pregnancy outcomes in systemic lupus erythematosus (SLE) |
| title_full | Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) in the prediction of poor pregnancy outcomes in systemic lupus erythematosus (SLE) |
| title_fullStr | Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) in the prediction of poor pregnancy outcomes in systemic lupus erythematosus (SLE) |
| title_full_unstemmed | Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) in the prediction of poor pregnancy outcomes in systemic lupus erythematosus (SLE) |
| title_short | Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) in the prediction of poor pregnancy outcomes in systemic lupus erythematosus (SLE) |
| title_sort | erythrocyte complement receptor 1 ecr1 and erythrocyte bound c4d ec4d in the prediction of poor pregnancy outcomes in systemic lupus erythematosus sle |
| url | https://lupus.bmj.com/content/9/1/e000754.full |
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