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• Persistence of aPL, looking for the holy grail
  Emmanuel Coloma-Bazán, Gerard Espinosa and Ricard Cervera
  Published on: 17 November 2020

• Published on: 17 November 2020

  Persistence of aPL, looking for the holy grail

  • Emmanuel Coloma-Bazán, Autoimmune Diseases Department Hospital Clinic
  • Other Contributors:
    • Gerard Espinosa, Autoimmune Diseases Departmen
    • Ricard Cervera, Autoimmune Diseases Department

  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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  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 from Khawaja et al. (1), the discontinuation of OAC in patients with APS associated with SLE would not be advisable.

  In a previous study (3), we described 11 patients with primary APS and low-risk aPL profile, who had their aPL persistently negative after thrombotic/obstetric morbidity manifestations, and in whom antithrombotic treatment was withdrawn. No new thrombotic events were observed after 20 months of follow-up.

  We want to point out two different characteristics between the present study and ours: 1) our study did not include patients with SLE-associated APS; therefore, the population target of the two cohorts are not comparable; and 2) patients included in our study had low-risk aPL profile defined by the presence of only two positive aPL determinations pre-thrombosis or obstetric morbidity.

  Zen et al. (4) described a small cohort of 16 patients with SLE-associated-APS in whom aPL became negative. Treatment with immunosuppressants was an independent predictor for negativization of aPL because they observed that seronegative patients received immunosuppressive therapy more frequently than patients with persistent positivity for aPL, suggesting downregulation of inflammatory pathways. Also, the immunomodulatory effect of antimalarials could contribute to aPL negativization during follow-up.

  Further research is, therefore, needed to determine if discontinuation of OAC could be accepted in some patients with APS (i.e., those with primary APS and low-risk aPL profile, who had their aPL persistently negative after thrombotic/obstetric morbidity manifestations).

  Declaration of conflicting interests
  The authors declared no potential conflicts of interest concerning the research, authorship, and publication of this article.

  Funding
  The authors received no financial support for the research, authorship, and publication of this article.

  References

  1. Khawaja M, Magder L, Goldman D, Petri MA. Loss of antiphospholipid antibody positivity post-thrombosis in SLE. Lupus Sci Med. 2020;7(1):1–7.
  2. Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019;78(10):1296–304.
  3. Coloma Bazán E, Donate López C, Moreno Lozano P, Cervera R, Espinosa G. Discontinuation of anticoagulation or antiaggregation treatment may be safe in patients with primary antiphospholipid syndrome when antiphospholipid antibodies became persistently negative. Immunol Res. 2013;56(2–3):358–61.
  4. Zen M, Loredo Martinez M, Benvenuti F, Gatto M, Saccon F, Larosa M, et al. Prevalence, outcome and management of patients with SLE and secondary antiphospholipid antibody syndrome after aPL seroconversion. Rheumatology. 2020;1–8.

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  Conflict of Interest:
  None declared.

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