OP0156 In Vitro Treatment with Anti-Cardiolipin and Anti-DSDNA Antibodies Modifies the Expression of Micrornas Related to Cardiovascular Disease in Patients with Antiphospholipid Syndrome and Systemic Lupus Erythematosus

2015 ◽  
Vol 74 (Suppl 2) ◽  
pp. 128.1-128
Author(s):  
C. Perez-Sanchez ◽  
M. Aguirre ◽  
P. Ruiz-Limόn ◽  
N. Barbarroja ◽  
Y. Jiménez-Gόmez ◽  
...  
Author(s):  
Alejandra María Patiño-Trives ◽  
Carlos Pérez-Sánchez ◽  
Laura Pérez-Sánchez ◽  
María Luque-Tévar ◽  
M. Carmen Ábalos-Aguilera ◽  
...  

Objective: Systemic lupus erythematosus (SLE) is associated to boosted atherosclerosis development and a higher cardiovascular disease risk. This study aimed to delineate the role of anti-double stranded DNA (anti-dsDNA) antibodies on the molecular profile and the activity of immune and vascular cells, as well as on their enhanced cardiovascular risk. Approach and Results: Eighty SLE patients were included. Extensive clinical/analytical evaluation was performed, including cardiovascular disease parameters (endothelial function, proatherogenic dyslipidemia, and carotid intima-media thickness). Gene and protein expression profiles were evaluated in monocytes from patients diagnosed positive or negative for anti-dsDNA antibodies by using NanoString and cytokine arrays, respectively. NETosis and circulating inflammatory profile was assessed in both neutrophils and plasma. Positivity and persistence of anti-dsDNA antibodies in SLE patients were associated to endothelial dysfunction, proatherogenic dyslipidemia, and accelerated atherosclerosis. In parallel, anti-dsDNA antibodies were linked to the aberrant activation of innate immune cells, so that anti-dsDNA(+) SLE monocytes showed distinctive gene and protein expression/activity profiles, and neutrophils were more prone to suffer NETosis in comparison with anti-dsDNA(−) patients. Anti-dsDNA(+) patients further displayed altered levels of numerous circulating mediators related to inflammation, NETosis, and cardiovascular risk. In vitro, Ig-dsDNA promoted NETosis on neutrophils, apoptosis on monocytes, modulated the expression of inflammation and thrombosis-related molecules, and induced endothelial activation, at least partially, by FcR (Fc receptor)-binding mechanisms. Conclusions: Anti-dsDNA antibodies increase the cardiovascular risk of SLE patients by altering key molecular processes that drive a distinctive and coordinated immune and vascular activation, representing a potential tool in the management of this comorbidity.


2014 ◽  
Vol 74 (7) ◽  
pp. 1441-1449 ◽  
Author(s):  
Carlos Perez-Sanchez ◽  
Nuria Barbarroja ◽  
Sebastiano Messineo ◽  
Patricia Ruiz-Limon ◽  
Antonio Rodriguez-Ariza ◽  
...  

ObjectiveTo identify shared and differential molecular pathways involved in the pathogenesis of atherosclerosis (AT) and cardiovascular disease (CVD) in systemic lupus erythematosus (SLE), primary antiphospholipid syndrome (APS) and APS associated with SLE (APS plus SLE).Methods129 patients (42 APS, 31 APS plus SLE and 56 SLE) and 61 healthy donors were included. Microarray expression profiling was performed in monocytes. RT-PCR of selected genes and western blot were used to validate microarray data. Clinical and inflammatory parameters were also analysed.ResultsCompared with controls, 555, 1224 and 518 genes were differentially expressed in monocytes from SLE, APS plus SLE and APS patients, respectively. Approximately 25–30% of differentially expressed genes were related to AT and CVD. Each disease displayed a specific AT/CVD/Inflammation-related gene signature. Compared with SLE, APS showed alterations in mitochondria biogenesis and function and oxidative stress. Besides the interferon signature, found in APS plus SLE and SLE patients, various genes mediating atherosclerotic/inflammatory signalling were also differentially expressed in APS plus SLE. IgG-anticardiolipin (aCL) titres independently predicted both atherosclerotic and thrombosis in APS plus SLE. Moreover, a significant correlation of IgG-aCL titres with mRNA levels of certain inflammatory molecules in monocytes was further noticed. In vitro treatment of monocytes with IgG-aCL promoted an increase in the expression of the genes most significantly changed in APS plus SLE versus healthy donors.ConclusionsGene expression profiling allows the segregation of APS, APS plus SLE and SLE, with specific signatures explaining the pro-atherosclerotic and pro-thrombotic alterations in these highly related autoimmune diseases.


GYNECOLOGY ◽  
2021 ◽  
Vol 23 (2) ◽  
pp. 167-172
Author(s):  
Galina A. Vlasova ◽  
Svetlana G. Perminova ◽  
Nadezhda M. Kosheleva

Aim. To assess the safety and efficacy of assisted reproductive technology (ART) programs in patients with systemic lupus erythematosus (SLE) with/without comorbid antiphospholipid syndrome (APLS). Materials and methods. The observational study included 26 patients with diagnosed SLE, of whom 7 women had comorbid APLS and disorders of reproductive function. The analysis of the causes of impaired fertility was based on history and comprehensive examination data, which, along with risk factors for possible complications, determined the choice of ART programs. Results. In 23 of 26 patients, infertility (primary: 14, secondary: 9) was diagnosed, and 3 patients were diagnosed with repeated miscarriage. The main etiological factors of infertility were tubal (n=6), male (n=8) and their combination (n=3); in 9 cases the etiology of infertility remained unclear. 10 patients with a history of lupus nephritis had a reduced ovarian reserve. In total, 23 infertile patients underwent 33 in vitro fertilization programs. 11 (33%) clinical pregnancies were registered, of which 7 ended in live birth. There were no cases of severe exacerbation of SLE and thrombotic complications. Conclusion. ART can be used in patients with SLE with / without APLS, if the underlying disease is compensated for and prevention for complications is used. The effectiveness of ART programs is comparable to that in the general population. Further research is needed to make a final judgment on the safety of various ART programs in SLE with/without APLS.


2017 ◽  
Vol 44 (5) ◽  
pp. 613-618 ◽  
Author(s):  
Pauline Orquevaux ◽  
Agathe Masseau ◽  
Véronique Le Guern ◽  
Vanessa Gayet ◽  
Danièle Vauthier ◽  
...  

Objective.To compile and assess data about complication and success rates forin vitrofertilization (IVF) of women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). To date, such data are sparse.Methods.This retrospective study described women with SLE and/or APS who have had at least 1 IVF cycle.Results.Thirty-seven women with SLE (n = 23, including 8 with antiphospholipid antibodies), SLE with APS (n = 4), or primary APS (n = 10) underwent 97 IVF procedures. For 43% of cases, the infertility was female in origin, for 19% male, 14% mixed, and 24% unexplained. No women had premature ovarian insufficiency because of cyclophosphamide. Median age at IVF was 34 years (range 26–46). The median number of IVF cycles was 2.6 (1–8). Patients were treated with hydroxychloroquine (72%), steroids (70%), azathioprine (3%), aspirin (92%), and/or low molecular weight heparin (62%). There were 27 (28%) pregnancies, 23 live births among 26 neonates (3 twin pregnancies), 2 miscarriages, and 2 terminations for trisomy 13 and 21. Six spontaneous pregnancies occurred during the followup. Finally, 26 women (70%) delivered at least 1 healthy child. Complications occurred in or after 8 IVF cycles (8%): SLE flares in 4 (polyarthritis in 3 and lupus enteritis in 1) and thromboembolic events in 4 others. One SLE flare was the first sign of previously undiagnosed SLE. Poor treatment adherence was obvious in 2 other flares and 2 thromboses. No ovarian hyperstimulation syndrome was reported.Conclusion.These preliminary results confirm that IVF can be safely and successfully performed in women with SLE and/or APS.


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