Autoimmune Liver Diseases and Antiphospholipid Antibodies Positivity: a Meta-analysis of Literature Studies

Ambrosino, Pasquale; Lupoli, Roberta; Spadarella, Gaia; Tarantino, Paolo; Minno, Alessandro Di; Tarantino, L.; Minno, Matteo Nicola Dario Di

doi:10.15403/jgld.2014.1121.amb

Cited by 28 publications

(16 citation statements)

References 43 publications

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“…Interestingly, the prevalence of HCC is increased in patients with SLE . Recently, liver disease was found to be associated with APS in our lupus cohort , a finding consistent with that in meta‐analyses of liver involvement in patients with APS . TAL is overexpressed in the T cells of SLE patients, which may be related to protection against oxidative stress .…”

Section: Resultssupporting

confidence: 88%

“…In summary, the model of lupus pathogenesis proposed herein involves mTORC1‐controlled mitochondrial dysfunction in the liver, with related generation of aPL and increased hepatocarcinogenesis in SLE . In support of this model, liver disease, which was defined as a ≥2‐fold elevation in the levels of aspartate aminotransferase or alanine aminotransferase, was associated with the production of aPL in our SLE cohort as well as in previous meta‐analyses . Along these lines, HCC develops in the liver following chronic inflammation, which is driven by mitochondrial oxidative stress and responds to treatment with rapamycin .…”

Section: Discussionsupporting

confidence: 73%

“…In a recent longitudinal study of patients with SLE, we observed a significant prevalence of liver disease, which was remarkably associated with the production of aPL . This finding is consistent with the data reported in meta‐analyses of liver involvement in patients with APS . Interestingly, treatment with rapamycin, which blocks the activation of mTORC1, prevented liver disease in our cohort of lupus patients .…”

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confidence: 92%

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Mitochondrial Dysfunction in the Liver and Antiphospholipid Antibody Production Precede Disease Onset and Respond to Rapamycin in Lupus‐Prone Mice

Oaks

Winans

Caza

et al. 2016

Arthritis & Rheumatology

109

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Background Anti-phospholipid antibodies (aPL) constitute a diagnostic criterion of systemic lupus erythematosus (SLE). aPL have been linked to liver disease in SLE. Since the mechanistic target of rapamycin (mTOR) is a regulator of oxidative stress, which contributes to the development of aPL, we examined the involvement of liver mitochondria in mouse lupus pathogenesis. Methods Mitochondria were isolated from lupus-prone MRL/lpr, C57BL/6.lpr and MRL mice, age-matched C57BL/6 negative controls, and transaldolase-deficient mice which exhibit oxidative stress in the liver. Electron transport chain (ETC) activity was assessed via oxygen consumption. ETC proteins, regulators of mitochondrial homeostasis, and mTOR complexes, mTORC1 and mTORC2, were examined by western blot. Anti-cardiolipin (ACLA) and anti-β2 glycoprotein I autoantibodies (anti-β2GPI) were measured by ELISA in mice treated with or without rapamycin. Results Mitochondrial oxygen consumption was increased in the liver of 4-week-old, disease-free MRL/lpr mice relative to age-matched controls. Mitophagy-initiator dynamin-related protein 1 (Drp1) was depleted while activity of mTORC1 was increased in MRL/lpr mice. In turn, mTORC2 activity was decreased in MRL and MRL/lpr mice. ACLA and anti-β2GPI levels were also elevated in 4-week-old MRL, C57BL/6.lpr, and MRL/lpr mice, preceding the development of nephritis. Transaldolase-deficient mice showed increased oxygen consumption, Drp1 depletion, mTORC1 activation, and elevated expression of NDUFS3, a pro-oxidant subunit of ETC complex I, as well as ACLA and anti-β2GPI production. Rapamycin selectively blocked mTORC1, NDUFS3 expression and aPL production both in transaldolase-deficient and lupus-prone mice. Conclusion mTORC-1-dependent mitochondrial dysfunction contributes to the generation of aPL and may represent a treatment target in SLE.

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Section: Resultssupporting

confidence: 88%

Section: Discussionsupporting

confidence: 73%

supporting

confidence: 92%

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Mitochondrial Dysfunction in the Liver and Antiphospholipid Antibody Production Precede Disease Onset and Respond to Rapamycin in Lupus‐Prone Mice

Oaks

Winans

Caza

et al. 2016

Arthritis & Rheumatology

109

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“…Altogether, our findings are in line with these experimental and clinical evidences, supporting the hypothesis that APS may be part of the clinical manifestations of hepatitis B and C. Similar results have been recently documented also in patients with autoimmune disorders [57,58], including autoimmune liver diseases [59]. Thus, the increased risk of thrombotic events due to aPL positivity may further contribute to the morbidity and mortality of patients with viral hepatitis and chronic liver diseases.…”

Section: Discussionsupporting

confidence: 91%

Viral hepatitis and anti-phospholipid antibodies positivity: A systematic review and meta-analysis

Ambrosino

Lupoli

Tarantino

et al. 2015

Digestive and Liver Disease

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“…Выявление аКл и aβ2GP1 в качестве диагностического показателя включено в лабораторные критерии антифосфолипидного синдрома (АФС) [19], а детекция аКл -в лабораторные критерии системной красной волчанки (СКВ) SLIСС 2012 [24]. Однако АФА обнаруживаются у пациентов с другими аутоиммунными, инфекционными и лимфопролиферативными заболеваниями, а также у здоровых доноров, не проявляя себя тромбозами или акушерской патологией [8,9,14,27,28]. По мнению ряда авторов [17], разные представители семейства АФА различаются по уровню патогенности, который также зависит от используемого лабораторного метода их определения.…”

Section: Introductionunclassified

Ranging of Antiphospolipid Antibodies in the Patients With Thrombophilia and Recurrent Miscarriage

et al. 2018

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Laboratory diagnosis of antiphospholipid syndrome (APS) is based on detection of antiphospholipid antibodies (aPLs). E.g., aPLs are directed against conformational epitopes of the so-called “co-factor” proteins: β2-gycoprotein 1 (β2-GP1), annexin V (An V) and prothrombin (Pt) that are formed during interaction with phospholipids – cardiolipin (CL), phosphatic acid (Pha), phosphatidylcholine (Pch), phosphatidylethanolamine (Pe), phosphatidylglycerol (Pg), phosphatidylinositol (Pi), phosphatidylserine (Ps). A routine methodology of detection based on ELISA testing is challenged by new tests when the antigen is absorbed on another kind of support like microbeads or membranes that can influence density of conformational epitopes for aPL’s binding. The aim of our study was to compare the results of aPLs detection by ELISA and multi-line immunodot assay (MLD). We collected blood serum samples from 45 patients with noncardioembolic ischemic strokes, 19 patients with recurrent deep vein thrombosis of lower limbs, 44 females with recurrent miscarriages, and 50 clinically healthy donors. To compare the results of aPL detection by ELISA and MLD kits, the test systems from different manufacturers were evaluated. We used an ELISA kits for detection of antibodies to CL IgG, aCL IgM, β2-GP1 produced by Euroimmun AG (Mr1) and Orgentec Diagnostica GmbH (Mr2) and MLD – for detection of antibodies to CL, β2-GP1, Pch, Pe, Pg, Pi, Ps, AnV and Pt (Medipan GmbH, Mr3). When a cut-off titer was used as the main index, 30.5% of patients were aPLs-positive with ELISA method by Mr1 and 38%, wiht Mr2. By MLD aPls were detected in 30% of patients. In the same cohort, medium and high aPLs titers (> 40 U/mL) were determined in 12% of patients using ELISA kits. Positive and highly positive aPLs titers were determined in 16% when using a new method by Mr3. Medium and high titer were detected only for antibodies to β2-GP1, CL, An V, Pha and Phs. The use of ELISA approach for detection of aPLs in patients with thrombosis and obstetric pathology is associated with relatively high number of low-positive ELISA results. Due to higher sensitivity for medium and high aPLs titers, MLD testing may be used as a confirming method for APS diagnosis.

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Autoimmune Liver Diseases and Antiphospholipid Antibodies Positivity: a Meta-analysis of Literature Studies

Cited by 28 publications

References 43 publications

Mitochondrial Dysfunction in the Liver and Antiphospholipid Antibody Production Precede Disease Onset and Respond to Rapamycin in Lupus‐Prone Mice

Mitochondrial Dysfunction in the Liver and Antiphospholipid Antibody Production Precede Disease Onset and Respond to Rapamycin in Lupus‐Prone Mice

Viral hepatitis and anti-phospholipid antibodies positivity: A systematic review and meta-analysis

Ranging of Antiphospolipid Antibodies in the Patients With Thrombophilia and Recurrent Miscarriage

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