Antiphospholipid syndrome and IgA anti-beta2-glycoprotein I antibodies: when Cinderella becomes a princess

Pérez, Dolores; Tincani, Anǵela; Serrano, Manuel; Shoenfeld, Yehuda; Serrano, Antonio

doi:10.1177/0961203317738227

Cited by 25 publications

(26 citation statements)

References 10 publications

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“…However, a recent study has revealed the opposite conclusion that IgA–aPL is associated with thrombosis and obstetric complications ( 10 ). Some other previous studies also have mentioned the robust association between IgA–aPL and thrombosis ( 13 , 39 – 42 ) and that even IgA–aβ 2 GPI can be used as an independent risk factor for the development of APS-related events ( 13 ) and should be included as a consensus criterion for the diagnosis of APS ( 43 ). These controversial conclusions can mainly be attributed to differences in the included criteria of the study population, ethnic distribution, or statistical methods of the study.…”

Section: Discussionmentioning

confidence: 98%

Immunoglobulin A Isotype of Antiphospholipid Antibodies Does Not Provide Added Value for the Diagnosis of Antiphospholipid Syndrome in a Chinese Population

Wang

et al. 2020

Front. Immunol.

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Objective Antiphospholipid syndrome (APS) is characterized by the presence of anti-phospholipid (aPL) antibodies. However, the relationship between the immunoglobulin (Ig) A isotype of aPL positivity and its clinical utility in APS diagnosis is controversial. Presently, we determine the clinical utility of IgA–aPL from consecutive patients in a large cohort from the Chinese population and patients with APS whose aPL profiles were obtained. Methods The detection of anticardiolipin (aCL) and anti-β 2 glycoprotein-Ⅰ (aβ 2 GPⅠ) antibodies of the IgA/IgG/IgM isotype by paramagnetic particle chemiluminescent immunoassay was carried out in sera from 7293 subjects. 153 primary APS (PAPS) patients and 59 patients with secondary APS (SAPS) were included in this study. Results In total, 1,082 out of 7,293 (2.55%) subjects had a positive IgA–aPL test, and the prevalence of isolated IgA–aPL was 0.29% (21/7,293) in the general population. The prevalence of IgA–aPL in the PAPS patients was 12.42% (19/153); however, only one patient (0.65%) presented with isolated IgA–aPL. Fifty (25.9%) of the SAPS had IgA–aPL, none of whom lacked IgG/IgM–aPL. The combination of the IgA isotype and the IgG/IgM isotype did not increase the diagnostic performance when compared with the IgG/IgM isotype of aCL or aβ 2 GPⅠ, respectively. IgA–aPL was not associated with clinical manifestation in patients with APS. Conclusion Isolated IgA–aPL is rare in the general population as well as in patients with APS. Whether in the laboratory or in clinical practice, the presence of IgA–aPL does not provide added value for the diagnosis of APS in the Chinese population.

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Section: Discussionmentioning

confidence: 98%

Immunoglobulin A Isotype of Antiphospholipid Antibodies Does Not Provide Added Value for the Diagnosis of Antiphospholipid Syndrome in a Chinese Population

Wang

et al. 2020

Front. Immunol.

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“…It also gives even more arguments to support that the IgA anti-β2GP1 antibodies are no longer the “Cinderella” (39) and that it is advisable to assess the possibility of including them in the APS classification criteria.…”

Section: Discussionmentioning

confidence: 99%

The IgA Isotype of Anti-β2 Glycoprotein I Antibodies Recognizes Epitopes in Domains 3, 4, and 5 That Are Located in a Lateral Zone of the Molecule (L-Shaped)

et al. 2019

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Background: Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with presence of anti-phospholipid antibodies (aPL). The APS classification criteria only consider the aPL of IgG/IgM isotype, however testing of aPL of IgA isotype is recommended when APS is suspected and consensus aPL are negative. IgA anti-βeta-2 glycoprotein-I (B2GP1) has been clearly related with occurrence of thrombotic events. Antibodies anti-B2GP1 of IgG/M isotypes recognize an epitope in Domain 1 (R39-G43), the epitopes that recognize IgA anti-B2GP1 antibodies are not well-identified. Aim: To determine the zones of B2GP1 recognized by antibodies of IgA isotype from patients with APS symptomatology and positive for IgA anti-B2GP1. Methods: IgA antibodies to Domain-1(D1) and Domain-4/5(D4/5) of B2GP1 (ELISA) and epitope mapping on oligopeptide arrays of B2GP1 were evaluated in sera from a group of 93 patients with at least one thrombotic and with isolated positivity for IgA anti-B2GP1 antibodies (negative for other aPL). Results: A total of 47 patients (50.5%) were positive for anti-D4/5 and 23(25%) were positive for anti-D1. When peptide arrays were analyzed, three zones of B2GP1 reactivity were identified for more than 50% of patients. The center of these zones corresponds to amino acids 140(D3), 204(D4), and 264(D5). The peptides recognized on D3 and D4 contain amino acid sequences sharing high homology with proteins of microorganism that were previously related with a possible APS infectious etiology. In the three-dimensional structure of B2GP1, the three peptides, as the R39-G43 epitope, are located on the right side of the molecule (L-shape). The left side (J-shape) does not bind the antibodies. Conclusions: Patients with thrombotic APS clinical-criteria, and isolated IgA anti-B2GP1 positivity appear to preferentially bind, not to the D1 or D4/5 domains of B2GP1, but rather to three sites in D3, D4, and D5. The sites on D3 and D4 were previously described as the target identified by human monoclonal antibodies derived from patients that were capable of inducing APS in animal models. The localization of these epitopes opens a new route to explore to increase understanding of the patholophysiology of the APS and to propose new alternatives and therapeutic targets.

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“…Currently, the IgA isotype is not included among the APS classification criteria of the APS, so that very few centers perform the IgA determination aB2GP1. For this reason, cases of IgA-mediated thrombosis are clearly underdiagnosed ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Pretransplant IgA-Anti-Beta 2 Glycoprotein I Antibodies As a Predictor of Early Graft Thrombosis after Renal Transplantation in the Clinical Practice: A Multicenter and Prospective Study

et al. 2018

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BackgroundGraft thrombosis is a devastating complication after renal transplantation. We recently described the association of anti-beta-2-glycoprotein-I (IgA-ab2GP1) antibodies with early graft loss mainly caused by thrombosis in a monocenter study.MethodsMulticenter prospective observational cohort study.Setting and participantsSeven hundred forty patients from five hospitals of the Spanish Forum Renal Group transplanted from 2000 to 2002 were prospectively followed-up for 10 years.OutcomesEarly graft loss and graft loss by thrombosis.MeasurementsThe presence of IgA anti-B2GP1 antibodies in pretransplant serum was examined using the same methodology in all the patients.ResultsAt transplantation, 288 patients were positive for IgA-B2GP1 (39%, Group-1) and the remaining were negative (Group-2). Graft loss at 6 months was higher in Group-1 (12.5 vs. 4.2% p < 0.001), vessel thrombosis being the most frequent cause of early graft loss, especially in Group-1 (6.9 vs. 0.4% p < 0.001). IgA-aB2GP1 was the most important independent risk factor for graft thrombosis (hazard ratio: 13.83; 95% CI: 3.17–60.27, p < 0.001). Furthermore, the, presence of IgA-aB2GP1 was associated with early graft loss and delayed graft function. At 10 years, survival figures were also lower in Group-1: graft survival was lower compared with Group-2 (60.4 vs. 76.8%, p < 0.001). Mortality was significantly higher in Group-1 (19.8 vs. 12.2%, p = 0.005).LimitationsPatients were obtained during a 3-year period (1 January 2000–31 December 2002) and kidneys were only transplanted from brain-dead donors. Nowadays, the patients are older and the percentage of sensitized and retransplants is high.ConclusionIn a prospective observational multicenter study, we were able to corroborate that pretransplant presence of IgA-aB2GP1 was the main risk factor for graft thrombosis and early graft loss. Therefore, a prospective study is needed to evaluate the efficacy and safety of prophylactic anticoagulation to avoid this severe complication.

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Antiphospholipid syndrome and IgA anti-beta2-glycoprotein I antibodies: when Cinderella becomes a princess

Cited by 25 publications

References 10 publications

Immunoglobulin A Isotype of Antiphospholipid Antibodies Does Not Provide Added Value for the Diagnosis of Antiphospholipid Syndrome in a Chinese Population

Immunoglobulin A Isotype of Antiphospholipid Antibodies Does Not Provide Added Value for the Diagnosis of Antiphospholipid Syndrome in a Chinese Population

The IgA Isotype of Anti-β2 Glycoprotein I Antibodies Recognizes Epitopes in Domains 3, 4, and 5 That Are Located in a Lateral Zone of the Molecule (L-Shaped)

Pretransplant IgA-Anti-Beta 2 Glycoprotein I Antibodies As a Predictor of Early Graft Thrombosis after Renal Transplantation in the Clinical Practice: A Multicenter and Prospective Study

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