Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Type I IFN Signature in Pregnant Patients with Lupus.

Andrade3,  Danieli, Koo3,  Gloria C., Redecha3,  Patricia, Kirou3,  Kyriakos A., Kim1,  Mimi, Crow3,  Mary K., Salmon2,  Jane E.

Albert Einstein College of Medicine, New York, NY
Hospital for Special Surgery, New York, NY
Hospital for Special Surgery, New York, NY

Purpose:

The cytokine milieu in SLE pregnancy is skewed towards a tolerant anti-infammatory state. Type I interferon (IFN) pathway is activated in many SLE patients and is associated with increased disease activity. That IFN-a has anti-angiogenic effects raises the possibility that it may be deleterious for pregnancy. We hypothesized that an IFN type I signature in pregnant lupus patients would be suppressed and if present, it would correlate with poor pregnancy outcomes.

Methods:

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. Exclusions were: prednisone >20mg, proteinuria >1gm/24 hr and creatinine >1.2 mg/dl. Subjects were evaluated and blood collected monthly beginning at <12 wks' gestation. Poor pregnancy outcome was defined as: fetal death >12 wks (n=3); placental insufficiency or preeclampsia (PE) (n=9), severe IUGR (n=4) or disease activity (n=2). Each of 18 patients with SLE and poor pregnancy outcomes (SLE/outcome) were matched 1:1:1 by age and ethnicity to an SLE patient with an uncomplicated pregnancy (SLE/no outcome) and a pregnant healthy control (HC). A total of 324 samples prospectively collected during pregnancy were tested. Serum samples from the 3 matched pregnancies were assayed simultaneously for IFN-a activity using a reporter cell assay (WISH assay) based on expression of IFN-regulated genes (MX1, IFIT1 and IF144). Data were compared between disease groups at each gestational time window with an ANOVA model. To examine the influence of PE in type I IFN signature in patients without autoimmune disease, we analyzed a second group of samples collected through pregnancy in 6 patients who developed PE and 6 controls with uncomplicated pregnancies.

Results:

Type I IFN signature was present throughout pregnancy in SLE patients compared to controls. Type I IFN score was higher in SLE patients without poor outcomes compared to controls (29.4 ± 14.73 vs 16.2 ± 6.71,18 pairs of patients, 230 samples, p=0.03) and it trended to be higher in SLE patients with poor outcomes compared to controls (38.4 ± 21.68 vs 16.2 ± 6.71, n= 18 pairs of patients, 209 samples, p=0.06). The two SLE groups did not differ significantly with respect to IFN signature. Mean SLEPDAI scores at enrollment were also not different between SLE with or without poor outcomes (4.1±3.4 vs. 2.1±2.9, respectively. SLE patients with PE showed a trend for increase in Type I IFN signature compared to non-autoimmune patients with PE, respectively. (55.13 ± 145 vs 8.93 ± 6.10, p= 0.09). In the non-autoimmune patients, the IFN signature did not differ between patients with and without PE (8.60 ± 6.36 vs 9.82 ± 2.52, p=0.91).

Conclusions:

Pregnancy does not abrogate the IFN signature in lupus patients. PE, in and of itself, is not associated with increase in type I IFN signature. The onset of proteinuria and increased blood pressure in pregnancy that is accompanied by a high Type I IFN score is suggestive of SLE flare rather than PE. Elevated type I IFN may help distinguish SLE from PE in pregnant patients.

Supported in part by NIH fund, NIH R01 AR49772 and Cnpq, 200591/2008-8.

To cite this abstract, please use the following information:
Andrade, Danieli, Koo, Gloria C., Redecha, Patricia, Kirou, Kyriakos A., Kim, Mimi, Crow, Mary K., et al; Type I IFN Signature in Pregnant Patients with Lupus. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1199
DOI: 10.1002/art.28965

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