Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Increased Relative Expression of the Interferon-Responsive Gene MX1 Is Present in Pregnant SLE Patients and May Distinguish Flare of SLE From Preeclampsia.
Andrade1, Danieli, Koo1, Gloria, Redecha1, Patricia M., Kirou2, Kyriakos A., Kim3, Mimi, Crow1, Mary K., Salmon4, Jane E.
Hospital for Special Surgery, New York, NY
Mary Kirkland Center for Lupus Care - Hospital for Special Surgery, New York, NY
Albert Einstein College of Medicine, Bronx, NY
Hospital for Special Surgery, Weill Cornell Medical College, New York, NY
Type I IFN (IFN-I) contributes to the pathogenesis of SLE. Elevated levels of IFN-I stimulated genes have been associated with increased disease activity. That IFN-a has anti-angiogenic effects raises the possibility that it may be deleterious for developing placenta in pregnant SLE patients. We hypothesized that MX1 (myxoma resistance protein 1), an IFN -I responsive gene, could be used as a single gene to determine the presence of IFN signature and predict outcomes in pregnant lupus patients.
We performed a nested case-control study of SLE patients in the PROMISSE Study- Predictors of Pregnancy Outcome: Biomarkers In Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus. Patients met ACR criteria for SLE. Exclusions were: prednisone >20mg, proteinuria >1gm/24 hr and creatinine >1.2 mg/dl. Each month, beginning at <12 wks gestation, SLEPDAI was measured and blood was collected. Poor pregnancy outcome was defined as: fetal death >12 wks; placental insufficiency or preeclampsia (PE), severe IUGR or severe hypertension. Each of 28 patients with SLE and poor pregnancy outcomes were matched 1:1:1 by age and ethnicity to an SLE patient with an uncomplicated pregnancy and a healthy pregnant control. Serum samples from 3 matched pregnancies were assayed simultaneously for IFN-a activity using a reporter cell assay. Real-time quantitative polymerase chain reaction was used to determine the RE of MX1 from samples obtained each month. To assess IFN-a activity in non-autoimmune patients destined for PE, we examined RE of MX1 through pregnancy in 11 healthy patients who developed PE and compared values to patients with SLE and PE as a pregnancy outcome. All analyses for Relative Expression (RE) of MX1 were done at 827 weeks of gestation and were expressed as medians.
In early pregnancy, RE of MX1 is higher in SLE patients with outcome than controls (p=0.0058) and tended to be higher in SLE patients with no poor outcome (p=0.08). SLE patients with PE showed higher levels of RE MX1 than controls, (p=0.0052) and than SLE patients with no outcomes (p=0.0094). There was no correlation between SLEPDAIs and RE MX1 before the outcome. RE of MX1 was not different in patients who were positive for anti-Ro. Hydroxychloroquine use was not associated with decreased expression of RE MX1 (p=0.529). SLE patients with PE showed higher RE MX1 compared to non-autoimmune patients with PE (p=0.0002).
RE of MX1 may be used as a single gene to detect the IFN signature in pregnant SLE patients. RE of MX1 can distinguish pregnant SLE patients from those without SLE. Pregnancy does not abrogate induction of IFN-a genes. Our data show that PE, in and of itself, is not associated with increased IFN-a, and that high levels of RE of MX1 may differentiate lupus nephritis from PE in pregnant patients with hypertension and proteinuria.
To cite this abstract, please use the following information:
Andrade, Danieli, Koo, Gloria, Redecha, Patricia M., Kirou, Kyriakos A., Kim, Mimi, Crow, Mary K., et al; Increased Relative Expression of the Interferon-Responsive Gene MX1 Is Present in Pregnant SLE Patients and May Distinguish Flare of SLE From Preeclampsia. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1443