Pregnancy Outcomes in Patients with Autoimmune Diseases and Anti-Ro/SSA Antibodies

Brucato, Antonio; Cimaz, Rolando; Caporali, Roberto; Ramoni, Vèronique; Buyon, Jill P.

doi:10.1007/s12016-009-8190-6

Cited by 177 publications

(132 citation statements)

References 101 publications

(124 reference statements)

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“…These data have been corroborated by numerous other studies (19,(21)(22)(23)(24)(25). Anti-Ro/SSA antibodies are associated with an increased risk of congenital heart block (1%-2%), neonatal lupus, and laboratory abnormalities, including hematologic (thrombocytopenia and neutropenia) and hepatic abnormalities (elevated transaminases), in asymptomatic infants within the first 27 days of life (26,27). Clinical remission of SLE activity and careful control of the disease are associated with improved outcomes, underlying the importance of careful monitoring of these patients throughout pregnancy (28)(29)(30).…”

Section: Sle and Pregnancysupporting

confidence: 68%

Obstetric Nephrology

Stanhope

White

Moder

et al. 2012

Clinical Journal of the American Society of Nephrology

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Summary SLE is a multi-organ autoimmune disease that affects women of childbearing age. Renal involvement in the form of either active lupus nephritis (LN) at the time of conception, or a LN new onset or flare during pregnancy increases the risks of preterm delivery, pre-eclampsia, maternal mortality, fetal/neonatal demise, and intrauterine growth restriction. Consequently, current recommendations advise that the affected woman achieve a stable remission of her renal disease for at least 6 months before conception. Hormonal and immune system changes in pregnancy may affect disease activity and progression, and published evidence suggests that there is an increased risk for a LN flare during pregnancy. The major goal of immunosuppressive therapy in pregnancy is control of disease activity with medications that are relatively safe for a growing fetus. Therefore, the use of mycophenolate mofetil, due to increasing evidence supporting its teratogenicity, is contraindicated during pregnancy. Worsening proteinuria, which commonly occurs in proteinuric renal diseases toward the end of pregnancy, should be differentiated from a LN flare and/or preeclampsia, a pregnancy-specific condition clinically characterized by hypertension and proteinuria. These considerations present challenges that underscore the importance of a multidisciplinary team approach when caring for these patients, including a nephrologist, rheumatologist, and obstetrician who have experience with these pregnancyrelated complications. This review discusses the pathogenesis, maternal and fetal risks, and management pertinent to SLE patients with new onset or a history of LN predating pregnancy.

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Section: Sle and Pregnancysupporting

confidence: 68%

Obstetric Nephrology

Stanhope

White

Moder

et al. 2012

Clinical Journal of the American Society of Nephrology

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“…A woman is at risk of delivering a baby affected by CHB if she is anti-SS-A positive. 11 Frequent surveillance by serial echocardiograms and obstetric sonograms between 16 to 20 weeks of gestation and thereafter is required for at-risk pregnancies. The goals are early diagnosis and early treatment of incomplete CHB, thus improving the outcome for the fetus.…”

Section: Antenatal Managementmentioning

confidence: 99%

Sjögren Syndrome and Pregnancy: A Literature Review

Gupta

2017

TPJ

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“…There are no data on spontaneous reversibility, and progression to advanced block has not been reproducibly documented to date. This is critical and investigators are encouraged to share echocardiographic tapes to validate the reliability of this candidate biomarker [32].…”

Section: Assessment Of First Degree Av Block In Uteromentioning

confidence: 99%

Arrhythmias Presenting in Neonatal Lupus

Brucato

Previtali

Ramoni

et al. 2010

Scandinavian Journal of Immunology

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Arrhythmogenicity and electrophysiological effects of anti-Ro ⁄ SSA antibodiesBased on the facts that there is no convincing evidence that maternal antibodies can cross the sarcolemma of a normal cardiac myocyte, essentially two major categories of mechanisms for congenital complete heart block (CHB) can be identified. The first is abnormal surface expression of intracellular SSA ⁄ Ro and SSB ⁄ La antigens, eventually induced by apoptosis [1, 2], viral infection [3], UV light and IFNc treatment [4]. The other mechanism is the cross-reactivity of maternal antibodies with targets other than SSA ⁄ Ro and SSB ⁄ La antigens. Maternal antibodies were reported to cross-react with laminin and with human cardiac myosin heavy chain at a critical stage during foetal cardiac development [5,6], but the L-type calcium channels seem particularly important in this hypothesis [7][8][9][10].After preliminary reports, [11,12] Boutjdir in an outstanding paper [7] showed that IgG-enriched fractions and anti-52-kD SSA ⁄ Ro antibodies affinity-purified from the sera of mothers whose children have CHB reversibly induce complete atrioventricular (AV) block in the human foetal heart perfused by the Langendorff technique. At 33 min of perfusion, complete AV block was observed with the presence of only P waves and missing QRS complexes. Reperfusion of the heart with antibodyfree Tyrode's solution for 48 min resulted in partial and slow recovery. Superfusion of hearts with IgG fractions from mothers with affected children also induced bradycardia and AV dissociation. In contrast, IgG from control mothers did not have any measurable effect on AV conduction. In the same paper, the authors showed that anti-Ro ⁄ SSA antibodies inhibit L-type Ca 2+ currents at the whole-cell and single-channel level. Immunization of female BALB ⁄ c mice with recombinant 52-kD SSA ⁄ Ro protein generated high-titre antibodies that crossed the placenta during pregnancy and were associated with varying degrees of AV conduction abnormalities, including complete AV block, in the pups. These findings suggest that anti-52-kD SSA ⁄ Ro antibodies are causally related to the development of CHB.The same group reported that the passive transfer of human anti-Ro/SSA into pregnant mice induced AbstractPerfusion of human foetal heart with anti-Ro ⁄ SSA antibodies induces transient heart block. Anti-Ro ⁄ SSA antibodies may cross-react with T-and L-type calcium channels, and anti-p200 antibodies may cause calcium to accumulate in rat heart cells. These actions may explain a direct electrophysiological effect of these antibodies. Congenital complete heart block is the more severe manifestation of so-called ''Neonatal Lupus''. In clinical practice, it is important to distinguish in utero complete versus incomplete atrioventricular (AV) block, as complete AV block to date is irreversible, while incomplete AV block has been shown to be potentially reversible after fluorinated steroid therapy. Another issue is the definition of congenital AV block, as cardiologists have considered co...

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Pregnancy Outcomes in Patients with Autoimmune Diseases and Anti-Ro/SSA Antibodies

Cited by 177 publications

References 101 publications

Obstetric Nephrology

Obstetric Nephrology

Sjögren Syndrome and Pregnancy: A Literature Review

Arrhythmias Presenting in Neonatal Lupus

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