Visualization of macro-immune complexes in the antiphospholipid syndrome by multi-modal microscopy imaging

Taatjes, Douglas J.; Bouffard, Nicole A.; Turkovich, Michele von; Quinn, Anthony S.; Wu, Xiao‐Xuan; Vasovic, Ljiljana V.; Rand, Jacob H.

doi:10.1016/j.micron.2017.04.005

Cited by 5 publications

(2 citation statements)

References 19 publications

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“…The immune complexes of aPL have been described previously ( 25 ) and they have recently been visualized with high resolution microscopy ( 26 ). Presence of immune complexes was associated with the occurrence of acute thrombotic events ( 27 – 29 ).…”

Section: Introductionmentioning

confidence: 99%

Presence of Immune Complexes of IgG/IgM Bound to B2-glycoprotein I Is Associated With Non-criteria Clinical Manifestations in Patients With Antiphospholipid Syndrome

et al. 2018

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Background: Antiphospholipid syndrome (APS) is an acquired autoimmune disorder defined by the presence of both clinical (thromboembolic events or pregnancy morbidity) and laboratory (antiphospholipid antibodies, aPL) manifestations. Despite their importance, several clinical manifestations strongly associated with APS such as livedo reticularis (LR), thrombocytopenia, sicca-ophthalmic(sicca), heart, or neurological manifestations are not included in the APS clinical classification criteria. Circulating immune complexes (CIC) formed by Beta-2-glycoprotein I (B2GPI) and aPL (B2-CIC) have been described and their presence has been related with thrombotic events.Methods: Cross-sectional and observational cohort study in APS patients with thrombotic symptomatology.Setting and Participants: Fifty-seven patients from the University Hospital Center Bezanijska Kosa (Belgrade, Serbia) who met the APS classification criteria (35 with primary APS and 22 with APS associated to systemic lupus erythematosus). This study aimed to determine the prevalence of B2-CIC in APS patients and to evaluate their association with clinical manifestations of APS not included in the classification criteria.Results: B2-CIC prevalence in APS patients was 19.3%. The presence of thrombocytopenia (OR:5.7), livedo reticularis (OR:5.6), sicca (OR:12.6), and leukopenia (OR:5.6) was significantly higher in patients with B2-CIC than in the rest of APS patients. C3 and C4 complement factor levels were significantly lower in B2-CIC positive patients, which suggests a greater consumption of complement. Patients with quadruple aPL positivity (triple aPL-positivity plus the presence of B2-CIC) showed a higher prevalence of thrombocytopenia, leucopenia and LR than those with single/double aPL-positivity. No significant differences were found in the frequencies observed in patients with triple-only vs. single/double aPL-positivity. There were no significant differences between patients with primary APS and lupus-associated APS regarding the prevalence of B2-CIC and outcomes.Conclusions: Presence of B2-CIC is strongly associated with several non-criteria clinical manifestations related to APS and to higher complement consumption. More studies are required to better understand the clinical significance of B2-CIC.

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Section: Introductionmentioning

confidence: 99%

Presence of Immune Complexes of IgG/IgM Bound to B2-glycoprotein I Is Associated With Non-criteria Clinical Manifestations in Patients With Antiphospholipid Syndrome

et al. 2018

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“…In agreement with these results, Taatjes et al. visualized the formation of immune-complexes using sera from APS patients by high resolution microscopy-based imaging techniques ( 29 ). Prior to these studies, a small number of reports were published that suggested the presence of B2-CIC in patients with SLE and APS by heparin affinity chromatography ( 30 , 31 ).…”

Section: Introductionmentioning

confidence: 63%

Circulating immune-complexes of IgG/IgM bound to B2-glycoprotein-I associated with complement consumption and thrombocytopenia in antiphospholipid syndrome

et al. 2022

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BackgroundAntiphospholipid syndrome (APS) is a multisystemic autoimmune disorder characterized by thrombotic events and/or gestational morbidity in patients with antiphospholipid antibodies (aPL). In a previous single center study, APS-related clinical manifestations that were not included in the classification criteria (livedo reticularis, thrombocytopenia, leukopenia) were associated with the presence of circulating immune-complexes (CIC) formed by beta-2-glycoprotein-I (B2GP1) and anti-B2GP1 antibodies (B2-CIC). We have performed a multicenter study on APS features associated with the presence of B2-CIC.MethodsA multicenter, cross-sectional and observational study was conducted on 303 patients recruited from six European hospitals who fulfilled APS classification criteria: 165 patients had primary APS and 138 APS associated with other systemic autoimmune diseases (mainly systemic lupus erythematosus, N=112). Prevalence of B2-CIC (IgG/IgM isotypes) and its association with clinical manifestations and biomarkers related to the disease activity were evaluated.ResultsB2-CIC prevalence in APS patients was 39.3%. B2-CIC-positive patients with thrombotic APS presented a higher incidence of thrombocytopenia (OR: 2.32, p=0.007), heart valve thickening and dysfunction (OR: 9.06, p=0.015) and triple aPL positivity (OR: 1.83, p=0.027), as well as lower levels of C3, C4 and platelets (p-values: <0.001, <0.001 and 0.001) compared to B2-CIC-negative patients. B2-CIC of IgM isotype were significantly more prevalent in gestational than thrombotic APS.ConclusionsPatients with thrombotic events and positive for B2-CIC had lower platelet count and complement levels than those who were negative, suggesting a greater degree of platelet activation.

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Reimagining the antiphospholipid syndrome, an enigmatic thrombophilic disorder, through the looking glass of microscopic imaging

Rand

Taatjes

2018

Histochem Cell Biol

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The antiphospholipid syndrome (APS) is an autoimmune thrombophilic disorder that was described as a diagnostic entity over 30 years ago. And yet the pathogenic mechanisms that are responsible for its clinical manifestations remain to be definitively established. The syndrome is defined by (1) the concurrence of vascular thrombosis and/or pregnancy complications together with (2) positivity for immunoassays and coagulation tests that were derived from clinical observations of two anomalous laboratory test results-specifically, false positivity for syphilis infection in uninfected individuals and the finding of inhibitors of blood coagulation in patients who lacked any bleeding tendencies. Over the years, these were standardized into immunoassays and coagulation assays for APS. Here, we describe how prior knowledge of the immunologic and coagulation aspects of the disorder led to research involving a range of imaging modalities including light microscopy, immunohistochemistry, confocal scanning laser microscopy, transmission and scanning electron microscopy, and atomic force microscopy. In turn, the results from those studies led to a "reimagining" of APS that has advanced the understanding of pathogenic mechanisms of the disorder and has led to the development of novel mechanistically based diagnostics along with potential new treatment approaches that target disease mechanisms.

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Visualization of macro-immune complexes in the antiphospholipid syndrome by multi-modal microscopy imaging

Cited by 5 publications

References 19 publications

Presence of Immune Complexes of IgG/IgM Bound to B2-glycoprotein I Is Associated With Non-criteria Clinical Manifestations in Patients With Antiphospholipid Syndrome

Presence of Immune Complexes of IgG/IgM Bound to B2-glycoprotein I Is Associated With Non-criteria Clinical Manifestations in Patients With Antiphospholipid Syndrome

Circulating immune-complexes of IgG/IgM bound to B2-glycoprotein-I associated with complement consumption and thrombocytopenia in antiphospholipid syndrome

Reimagining the antiphospholipid syndrome, an enigmatic thrombophilic disorder, through the looking glass of microscopic imaging

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