Anti-Phosphatidylethanolamine and Anti-Phosphatidylserine Antibodies—Association with Renal Involvement, Atherosclerosis, Cardiovascular Manifestations, Raynaud Phenomenon and Disease Activity in Polish Patients with Systemic Lupus Erythematosus

Fischer, Katarzyna; Przepiera-Będzak, Hanna; Brzosko, Iwona; Sawicki, Marcin; Walecka, Anna; Brzosko, Marek

doi:10.3390/biom12101328

Cited by 5 publications

(5 citation statements)

References 56 publications

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“…PS-specific IgG has been detected in patients with SLE, APS and systemic sclerosis/scleroderma (SSc) [8,10,13,14]. Recent cohort studies have reported the existence of PS-specific IgG in severe COVID-19 patients [6].…”

Section: Discussionmentioning

confidence: 99%

“…As one of the most severe manifestations in SLE patients, LN is initiated by renal immune-complex deposition and lymphocytic infiltration [12]. In SLE patients, the levels of phosphatidylserine (PS)specific phospholipase A1 and anti-PS antibodies are elevated and involved in lupus progression with multiple immunomodulatory effects [13,14]. However, it is unclear which B-cell subsets produce anti-PS antibodies and whether anti-PS antibodies contribute to tissue damage and nephropathy during SLE development.…”

Section: Introductionmentioning

confidence: 99%

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B1-cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation

Ma¹,

Du²,

Wang³

et al. 2023

Cell Mol Immunol

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Autoantibodies produced by B cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). However, both the cellular source of antiphospholipid antibodies and their contributions to the development of lupus nephritis (LN) remain largely unclear. Here, we report a pathogenic role of anti-phosphatidylserine (PS) autoantibodies in the development of LN. Elevated serum PS-specific IgG levels were measured in model mice and SLE patients, especially in those with LN. PS-specific IgG accumulation was found in the kidney biopsies of LN patients. Both transfer of SLE PS-specific IgG and PS immunization triggered lupus-like glomerular immune complex deposition in recipient mice. ELISPOT analysis identified B1a cells as the main cell type that secretes PS-specific IgG in both lupus model mice and patients. Adoptive transfer of PS-specific B1a cells accelerated the PS-specific autoimmune response and renal damage in recipient lupus model mice, whereas depletion of B1a cells attenuated lupus progression. In culture, PS-specific B1a cells were significantly expanded upon treatment with chromatin components, while blockade of TLR signal cascades by DNase I digestion and inhibitory ODN 2088 or R406 treatment profoundly abrogated chromatin-induced PS-specific IgG secretion by lupus B1a cells. Thus, our study has demonstrated that the anti-PS autoantibodies produced by B1 cells contribute to lupus nephritis development. Our findings that blockade of the TLR/Syk signaling cascade inhibits PS-specific B1-cell expansion provide new insights into lupus pathogenesis and may facilitate the development of novel therapeutic targets for the treatment of LN in SLE.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

B1-cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation

Ma¹,

Du²,

Wang³

et al. 2023

Cell Mol Immunol

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show abstract

“…PS-speci c IgG has been detected in SLE, APS and SSc. 8,10,13,14 Recent cohort studies have reported the existence of PS-speci c IgG in severe COVID-19 patients. 6 The prevalence of the antiphospholipid antibodies (aPL) associates with thrombosis, complications of pregnancy, and neurologic disorders in SLE patients.…”

Section: Discussionmentioning

confidence: 99%

“…12 In SLE patients, levels of phosphatidylserine (PS)-speci c phospholipase A1 and anti-PS antibodies are elevated and involved in lupus progression with multiple immunomodulatory effects. 13,14 However, it has been unclear which B cell subsets produce anti-PS antibodies and whether anti-PS antibodies contribute to tissue damage and nephropathy during SLE development.…”

Section: Introductionmentioning

confidence: 99%

B1 cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation

et al. 2023

Preprint

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Autoantibodies produced by B cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). However, both the cellular source of anti-phospholipid antibodies and their contributions to the development of lupus nephritis (LN) remain largely unclear. Here, we report a pathogenic role ofanti-phosphatidylserine (PS) autoantibodies in the development of LN. In cohort study and mouse models, elevated serum PS-specific IgG levels were detected in SLE patients, especially in those with nephritis, and lupus mice. The deposition of PS-specific IgG was detected in kidney biopsied of lupus nephritis patients. Both transfer of SLE PS-specific IgG and PS immunization triggered lupus-like glomerular immune complex deposition in recipient mice. ELISPOT analysis identified B1a cells as the main cell type for secreting PS-specific IgG in both lupus mice and patients. Adoptive transfer of PS-specific B1a cells accelerated PS-specific autoimmune response and renal damage in recipient lupus mice whereas depletion of B1a cells attenuated lupus progression. In culture, PS-specific B1a cells were significantly expanded upon treatment with chromatin components while blockade of TLR signal cascades by DNase I digestion, inhibitory ODN 2088 or R406 treatment profoundly abrogated chromatin-induced PS-specific IgG secretion by lupus B1a cells. Thus, our study has demonstrated that the novel anti-PS autoantibodies produced by B1 cells contribute to lupus nephritis development. Our findings that blockade of TLR/Syk signaling cascade inhibits PS-specific B1 cell expansion may provide new insight in understanding lupus pathogenesis and may help develop novel therapeutic targets for the treatment of LN in SLE.

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“…The presence of APL may be associated with thrombus formation, which can lead to thrombosis and thrombocytopenia. These antibodies are related to early atherosclerosis and correlate significantly with cIMT in clinical studies [40,[139][140][141]. A summary of impact of antibodies on endothelial dysfunction and atherogenesis in SLE is provided in Table 2.…”

Section: Antibodiesmentioning

confidence: 99%

Update of Potential Biomarkers in Risk Prediction and Monitoring of Atherosclerosis in Systemic Lupus Erythematosus to Prevent Cardiovascular Disease

Blachut,

Przywara-Chowaniec,

Tomasik

et al. 2023

Biomedicines

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Systemic lupus erythematosus is a chronic connective tissue disease associated with an increased risk of premature atherosclerosis. It is estimated that approximately 10% of SLE patients develop significant atherosclerosis each year, which is responsible for premature cardiovascular disease that is largely asymptomatic. This review summarizes the most recent reports from the past few years on biomarkers of atherosclerosis in SLE, mainly focusing on immune markers. Persistent chronic inflammation of the vascular wall is an important cause of cardiovascular disease (CVD) events related to endothelial dysfunction, cell proliferation, impaired production and function of nitric oxide and microangiopathic changes. Studies on pathogenic immune mediators involved in atherosclerosis will be crucial research avenues for preventing CVD.

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Anti-Phosphatidylethanolamine and Anti-Phosphatidylserine Antibodies—Association with Renal Involvement, Atherosclerosis, Cardiovascular Manifestations, Raynaud Phenomenon and Disease Activity in Polish Patients with Systemic Lupus Erythematosus

Cited by 5 publications

References 56 publications

B1-cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation

B1-cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation

B1 cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation

Update of Potential Biomarkers in Risk Prediction and Monitoring of Atherosclerosis in Systemic Lupus Erythematosus to Prevent Cardiovascular Disease

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