6 e-Letters

published between 2017 and 2020

  • Persistence of aPL, looking for the holy grail

    To the editor,

    We have read with interest the study from Khawaja et al. entitled ''Loss of antiphospholipid antibody (aPL) positivity post-thrombosis in systemic lupus erythematosus (SLE)''(1). The authors described 31 patients with antiphospholipid syndrome (APS) associated with systemic lupus erythematosus who presented loss of antiphospholipid antibodies (aPL) positivity after thrombotic events.

    They measured four types of aPL: IgM, IgG and IgA isotypes of anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). Complete disappearance after thrombosis was observed in 41% of APS patients for IgG aCL, 51% for those with IgM aCL, 50% for IgA aCL, and 20% for LAC. However, 60% of those who at the same time lost IgG aCL and 76% of those who became negative for LAC, reacquired the antibodies within five years. In contrast, only 37% and 17% of those who lost IgM or IgA aCL, reacquired the antibodies within five years, respectively. Finally, 14 (45%) patients never turned back positive during the follow-up period. They concluded that recurrence of aPL positivity is frequent in APS associated with SLE, after their disappearance in post-thrombotic states.

    Until now, long term oral anticoagulation (OAC) is the cornerstone of treatment for thrombotic primary and SLE-associated APS (2). The decision to withdraw OAC in APS patients when aPL become "persistently" negative remains a matter of debate. In the light of results fro...

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  • Overcoming the challenges in new lupus diagnostics

    Dr Olsen and Karp have summarised data from several important papers on the use of novel diagnostic tests for earlier diagnosis of SLE. I agree in the importance of this problem, for the early exclusion of SLE in people with benign ANA positivity, and early intervention in people destined to develop SLE or related disease.

    I also agree with the key challenges in such research. Previous studies have been limited by a retrospective design. Inclusion of patients with variable symptom duration or patient populations that were selected for certain clinical characteristics may bias findings by conditioning on the outcome. Also, putative biomarker results need to be appraised alongside routine diagnostic tests, not in isolation.

    These challenges were met in our previous study into these questions[1]. We invited all ANA-positive referrals to our centre with an onset of the symptoms that triggered referral within the past 12 months to participate, ensuring an unbiased sample appropriate to the clinical question. We collected detailed data on clinical presentation, routine immunology assessments, patient and physician reported severity, and family history, and integrated these data into our biomarker evaluation. Our patients were recruited and followed up prospectively in a standardised schedule of visits with strict assessment of criteria and a "flare hotline" in case new symptoms developed.

    By doing so, we were able to reliably demonstrate the value...

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  • SLE and Atherosclerosis: There Are Several Mechanisms To Highlight

    Dear editor;
    We have read with great interest the article published by Haque et al. which was about association between atherosclerotic process, cardiovascular outocomes and systemic lupus erythematosus (SLE). It is reported that only SDI score, triglyceride level and cyclophosphamide exposure was predictive for future cardiovascular events and factors related with plaque progression were defined(1).
    SLE is a multisystemic disorder and lupus nephritis is one of the main manifestions of the disease. It usually presents with proteinuria and deteriorated renal glomerular functions. Renin angiotensinogen antgiotensin system (RAAS) inhibitors are used in patients with lupus nephritis to reduce proteinuria and kidney function protection(3). Angiotensin II (AT II) has unfavorable effects on endothelial functions. AT II binds AT 1 receptors and promotes vasoconstriction and production of proinlammatory cytokines and proliferation factors. It is shown by several studies that RAAS inhibitors improves endothelial functions and induces the regression of atherosclerotic process(3).
    Microalbuminuria (MAU) and proteinuria are related with worse cardiovascular outcomes. Microalbuminuria causes endothelial dysfunction and associated with accelerated atherosclerosis(4). MESA study demonstrated that coronary calcification is significantly higher in patients with microalbuminuria than counterparts without MAU. Not only presence but also amount of MAU is associated with insu...

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  • Comment on: TNF-α and plasma albumin as biomarkers of disease activity in systemic lupus erythematosus

    Dear editor,
    We read with interest the article of Idborg et al.1 who recently analyzed the role of several inflammatory mediators, and their usefulness as biomarkers in the measurement of activity of disease and the identification of clinical subphenotypes in systemic lupus erythematosus (SLE). Although interesting, these results may benefit of further discussion in light of systems medicine.
    Authors concluded that the two main inflammatory mediators related with activity of SLE were TNF-α and p-albumin. However, previous studies have found that TNF-α and the TNF/IL-10 ratio were higher in patients with low activity of disease,2 and that TNF-α antagonists may induce SLE-like disease.3 These controversial data argues against a generalized model based on TNF-α as clinical activity biomarker, and advocate for the influence of other mediators in such a condition.
    As shown by Idborg et al., IL-6, IL-10, IL-15, MCP-1, IP-10, MIP-1α, ESR, anti-dsDNA and U-albumin/creatinine were also positively correlated with activity of disease,1 suggesting that the exclusive role of TNF-α and p-albumin on activity of disease is unlikely. In fact, the pathological functions of these biomarkers are not isolate since they emerge from the interactions among them and between cells and tissues (i.e., systems medicine).4
    In this sense, cytokine and autoantibody clusters (i.e., neutral, chemotactic/anti-phospholipid antibodies, and IFN-α/dsDNA) have been reported to be associat...

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  • Response to Editorial

    The Editor,
    Lupus Science and Medicine
    BMJ Journals

    Dear Madam/Sir,

    Our esteemed peer Dr. Boers has editorialised1 on our recently published study of associations of glucocorticoid use with damage accrual in SLE2, suggesting that studies of the type reported are ‘harmful’. As this is such a serious accusation, we feel compelled to respond, even though we suspect that in the end the views of the authors and of Dr Boers as serious physician-researchers are in fact highly aligned. Essentially, we do not resile from our view that long-term reliance on glucocorticoids for the control of inflammation in SLE carries harm, and that steroid-reducing regimens for SLE management are urgently needed. At no time in our report, and certainly not in our clinical practice, do we advise against the use of these drugs, though such an imprecation was implied (incorrectly) in Dr Boers’ editorial. Rather, it is our view that strategies to achieve control of disease activity with reduced reliance on glucocorticoids, such as improving the use of non-glucocorticoid agents or the introduction of novel therapies, are as urgently needed as ever – and that complacency about the chronic use of glucocorticoids in SLE is not an acceptable status quo.

    As we stated in the opening remarks, ‘The objective of the present study was to quantify damage accrual in a prospectively followed cohort of patients with SLE and determine the association of glucocorticoid use with damage...

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  • Prolonged QT interval and atherosclerosis in systemic lupus erythematosus

    Geraldino-Pardillaet al.1 recently published an interesting article analysing one of the most important aspects of systemic lupus erythematosus (SLE): the risk of cardiovascular disease, a leading cause of death in SLE patients. Although there were no healthy control group to compare, and the SLE patient sample size was limited, their conclusions are clinically valuable and should be taken into consideration.

    The usefulness of the corrected QT interval (QTc) as a marker of atherosclerosis risk is well-established in the general population and in some sub-groups with high cardiovascular risk. QTc prolongation is also linked to cardiovascular events and mortality during follow-up2-3. QTc interval prolongation in SLE patients has been described in previous studies4.However, no data on the clinical repercussions of this finding are available. Our research group recently published a paper on the positive correlation between QTc interval prolongation in SLE patients and higher arterial stiffness measured by pulse-wave velocity5. The association was independent of hypertension and age. Our data complement those published by Geraldino-Pardilla et al.1, suggesting an independent association between QTc interval prolongation and subclinical atherosclerosis. However, there is no evidence of the long-term clinical effects of this association. Prospective studies with large sample sizes and long follow-up periods are required to study the potential long-term effects. In any case...

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