Seronegative antiphospholipid syndrome: refining the value of “non-criteria” antibodies for diagnosis and clinical management

Pignatelli, Pasquale; Ettorre, Evaristo; Menichelli, Danilo; Pani, Arianna; Violi, Francesco; Pastori, Daniele

doi:10.3324/haematol.2019.221945

Cited by 95 publications

(105 citation statements)

References 81 publications

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“…Other noncriteria aPL like antiphosphatidylethanolamine, negatively charged phospholipids (other than cardiolipin), antivimentin/cardiolipin, Annexin A5, and aPS/ prothrombin (PT) antibodies have been suggested to be clinical relevant in patients suspected of APS, but negatively tested for consensus aPL. 33 A recent systematic review showed a strong association between aPS/PT aPL and clinical manifestations of APS, with a high association with LAC. 34 However, this needs to be validated in a large multicenter study.…”

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confidence: 99%

Is There an Additional Value in Detecting Anticardiolipin and Anti-β2 glycoprotein I IgA Antibodies in the Antiphospholipid Syndrome?

et al. 2020

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Background Anticardiolipin (aCL) and anti-β2 glycoprotein I (aβ2GPI) immunoglobulin A (IgA) antiphospholipid antibodies (aPL) have shown to associate with thrombosis and pregnancy morbidity. However, inclusion of IgA aPL in the classification criteria of the antiphospholipid syndrome (APS) has been debated. We investigated the value of aCL and aβ2GPI IgA aPL in the detection of thrombosis and pregnancy morbidity in addition to the current aPL panel for APS. Methods We included 1,068 patients from eight European medical centers: 259 thrombotic APS patients, 122 obstetric APS patients, 204 non-APS thrombosis patients, 33 non-APS obstetric patients, 60 APS patients with unspecified clinical manifestations, 196 patients with autoimmune diseases, and 194 controls. aCL and aβ2GPI IgG/M/A were detected with four commercial assays and lupus anticoagulant was determined by the local center. Results Positivity for IgA aPL was found in 17 to 26% of the patients with clinical manifestations of APS and in 6 to 13% of the control population. Both aCL and aβ2GPI IgA were significantly associated with thrombosis and pregnancy morbidity. Isolated IgA positivity was rare in patients with clinical manifestations of APS (0.3–5%) and not associated with thrombosis and/or pregnancy morbidity. Addition of IgA to the current criterion panel did not increase odds ratios for thrombosis nor pregnancy morbidity. Conclusion aCL and aβ2GPI IgA are associated with clinical manifestations of APS. However, isolated IgA positivity was rare and not associated with thrombosis or pregnancy morbidity. These data do not support testing for aCL and aβ2GPI IgA subsequent to conventional aPL assays in identifying patients with thrombosis or pregnancy morbidity.

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confidence: 99%

Is There an Additional Value in Detecting Anticardiolipin and Anti-β2 glycoprotein I IgA Antibodies in the Antiphospholipid Syndrome?

et al. 2020

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“…Of note anti P-acid was linked with thrombosis in several studies which evaluated mostly IgG antibodies and regarded thrombosis in general both arterial and venous. In a recent study of seronegative APS patients, anti P-acid was linked with fetal losses and not with thrombosis 48 . Further studies are required to verify such an inverse correlation.…”

Section: Discussionmentioning

confidence: 90%

Profiles of criteria and non-criteria anti-phospholipid autoantibodies are associated with clinical phenotypes of the antiphospholipid syndrome

Levin

Volkov

Seguro

et al. 2020

Preprint

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Background: Specific anti-phospholipids antibodies (aPLs) are used as classification criteria of the antiphospholipid syndrome (APS). These aPLs, although essential for diagnosis, do not predict disease phenotypes, which may require specific therapies. Non-criteria aPLs are rarely evaluated and their role is yet to be defined. In the current study, we aimed to examine the association between criteria and non-criteria aPLs and APS phenotypes.Methods: Serum samples from 188 subjects, 130 APS patients and 58 controls were analyzed for the presence of 20 aPLs (IgG and IgM isotypes to cardiolipin(CL), beta2-glycoprotein1(β2GP1), phosphatidic acid(P-acid), phosphatidylcholine(PC), phosphatidylethanolamine(PE), phosphatidylglycerol(PG), phosphatidylinositol(PI), phosphatidylserine(PS), annexin-5(AN) and prothrombin(PT) using a line immunoassay (GA Generic Assays, Germany). Sero-positivity to the different aPLs/aPLs profiles was correlated to APS phenotypes (i.e. arterial thrombosis, CNS manifestations, venous thrombosis, relapsing disease, obstetric morbidity). Results: In this cohort, arterial thrombosis was associated with accumulative number of ≥7/20 aPLs evaluated (OR 4.1; CI95% 1.9-96, p=0.001) as well as the sole presence of aPT(IgG) (OR 2.3;CI 95% 1.1-5.1, p=0.03). CNS manifestations were linked with a profile of 4 aPLs(IgG): aPT, aPG, aPI and aAN (OR 2.6;CI 95% 1.1-6.3, p=0.03). Symptom-free period of ≥3 years was linked with lower number of aPLs and the presence of aPI(IgG) (OR 3.0;CI 95% 1.08-8.1, p<0.05) or aAN(IgG) (OR 3.4;CI 95% 1.08-10.9, p<0.05). APS related pregnancy morbidity correlated with a profile of 2 aPLs(IgG): aCL and aPS (OR 2.9; CI95% 1.3-6.5, p<0.05) or the sole presence of aAN(IgG) (OR 2.8; CI95% 1.02-8, p=0.05). Conclusion: In this study, we observed an association between specific criteria/non-criteria aPLs or aPLs profiles and clinical phenotypes of APS. Our data suggest that examination of a wider variety of aPLs may allow better characterization of APS.

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“…Our patient with ASIA-MMPA apparently had criteria for APS; however, he had low aCL levels and LA were weakly to moderately present, this disagreement has been controversial and currently these patients can be considered as seronegative APS. 6 On the other hand, DLBCL increased the risk of thrombosis. In fact, cancer enhances the risk of thrombogenesis and aPL per se may contribute to an increased risk of thrombosis in patients with lymphoproliferative disease.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune/inflammatory syndrome induced by methylmethacrylate associated to seronegative antiphospholipid syndrome and diffuse large B-cell non-Hodgkin’s lymphoma

Vera‐Lastra

Rojas-Milán

Peralta-Amaro

et al. 2020

Lupus

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Background Autoimmune/inflammatory syndrome induced by adjuvants has been associated with different substances used for cosmetic purposes; for example, silicone, methylmethacrylate, autoimmune disorders and cancer. Discussion A 40-year-old man with a prior history of methylmethacrylate injection in the buttocks for aesthetic purposes 8 years ago, presented with deep venous thrombosis in the left leg 6 months ago, accompanied with inflammation, hardening, changes in colour, ulceration in the buttocks, arthritis, myalgias and fever. Weak and moderate lupus anticoagulant and low levels of anticardiolipin antibodies were present. Thoracoabdominal tomography showed hepatosplenomegaly and a pulmonary nodule, the biopsy of which showed chronic granulomatous inflammation. After a month, a new chest tomography showed multiple nodular pulmonary lesions. The new pulmonary biopsy showed a diffuse large B-cell non-Hodgkin’s lymphoma which was treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab for four cycles, with good response of the autoimmune/inflammatory syndrome, but partial response of the diffuse large B-cell non-Hodgkin’s lymphoma. Conclusion We describe the first case of seronegative antiphospholipid syndrome and lymphoma associated with methylmethacrylate in a patient with autoimmune/inflammatory syndrome.

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Seronegative antiphospholipid syndrome: refining the value of “non-criteria” antibodies for diagnosis and clinical management

Cited by 95 publications

References 81 publications

Is There an Additional Value in Detecting Anticardiolipin and Anti-β2 glycoprotein I IgA Antibodies in the Antiphospholipid Syndrome?

Is There an Additional Value in Detecting Anticardiolipin and Anti-β2 glycoprotein I IgA Antibodies in the Antiphospholipid Syndrome?

Profiles of criteria and non-criteria anti-phospholipid autoantibodies are associated with clinical phenotypes of the antiphospholipid syndrome

Autoimmune/inflammatory syndrome induced by methylmethacrylate associated to seronegative antiphospholipid syndrome and diffuse large B-cell non-Hodgkin’s lymphoma

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