Lipid Anti-Lipid Antibody Responses Correlate with Disease Activity in Systemic Lupus Erythematosus

Jovanović, Vojislav; Aziz, Nurhuda Abdul; Lim, Yan Ting; Poh, Amanda Ng Ai; Chan, Sherlynn Jin Hui; Pei, Eliza Ho Xin; Lew, Fei Chuin; Shui, Guanghou; Jenner, Andrew; Li, Bowen; McKinney, Eoín; Lyons, Paul; Kemeny, David M.; Smith, Kenneth G. C.; Wenk, Markus R.; MacAry, Paul A.

doi:10.1371/journal.pone.0055639

Cited by 15 publications

(12 citation statements)

References 58 publications

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“…Germinal centers provide the microenvironmental requirements for the interactions between follicular T and B cells that lead to the generation of high-affinity IgG antibodies against protein antigens ( 12 ). IgG antibodies against several lipids (lathosterol, 7-α-hydroxycholesterol, cardiolipin, and oxidized PC) have been found in SLE patients ( 27 ), and IgG antibodies against long-chain saturated fatty acids have been found in the sera of patients with type 2 diabetes ( 28 ). IgM and IgG anti-cholesterol antibodies have been detected even in healthy individuals, as well as in patients with atherosclerosis and viral infections ( 29 – 31 ).…”

Section: Discussionmentioning

confidence: 99%

Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Wong-Baeza

Reséndiz-Mora²,

Donis-Maturano

et al. 2016

Front. Immunol.

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Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate in vivo the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1−, CD19−, CD138+) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD−, CD19+, PNA+) specific for NPA in the draining lymph nodes and the spleen, and we identified in situ the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220+, Blimp1+) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers.

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Section: Discussionmentioning

confidence: 99%

Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Wong-Baeza

Reséndiz-Mora²,

Donis-Maturano

et al. 2016

Front. Immunol.

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“…Similarly, modification of individual nucleotide bases, single-strand breaks and cross-linking are the typical effects of ROS on nucleic acids. All these interactions of ROS with protein, lipid and nucleic acid are involved in auto-antibody formation in SLE patients [ 13 , 63 ]. Table 2 summarizes the important studies on antibodies formation against modified lipid, protein and DNA in SLE patients.…”

Section: Reviewmentioning

confidence: 99%

“…Increased MDA (malondialdehyde)-modified proteins, anti-SOD and anti-catalase antibodies, albumin modification by HNE (4-hydroxy 2-nonenal) in the sera of SLE patients are associated with disease activity in SLE patients [ 11 , 12 ]. Levels of F2 isoprostane (8-iso-PGF2), a derivative of lipid peroxidation, increased in urine from SLE patients and are associated with disease activity [ 13 ]. Many independent studies show the elevated levels of MDA, F2-Isoprostane, nitric oxide and diminished levels of reduced glutathione in patients with lupus nephritis [ 14 - 17 ].…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress and its biomarkers in systemic lupus erythematosus

et al. 2014

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Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease whose etiology remains largely unknown. The uncontrolled oxidative stress in SLE contributes to functional oxidative modifications of cellular protein, lipid and DNA and consequences of oxidative modification play a crucial role in immunomodulation and trigger autoimmunity. Measurements of oxidative modified protein, lipid and DNA in biological samples from SLE patients may assist in the elucidation of the pathophysiological mechanisms of the oxidative stress-related damage, the prediction of disease prognosis and the selection of adequate treatment in the early stage of disease. Application of these biomarkers in disease may indicate the early effectiveness of the therapy. This review is intended to provide an overview of various reactive oxygen species (ROS) formed during the state of disease and their biomarkers linking with disease. The first part of the review presents biochemistry and pathophysiology of ROS and antioxidant system in disease. The second part of the review discusses the recent development of oxidative stress biomarkers that relates pathogenesis in SLE patients and animal model. Finally, this review also describes the reported clinical trials of antioxidant in the disease that have evaluated the efficacy of antioxidant in the management of disease with ongoing conventional therapy.

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“…In untreated MS patients, we found an inverse correlation between anti-oxLDL antibodies and CD 14+ IL6+ cells. In systemic lupus erythematosus, recent studies have described anti-oxidized-lipid antibodies associated to a better disease prognosis (36). In different studies, we and others describe higher anti-oxLDL in benign MS patients (12).…”

Section: Discussionmentioning

confidence: 84%

The Peripheral Network between Oxidative Stress and Inflammation in Multiple Sclerosis

Gironi

Borgiani

Cursano³

et al. 2014

Eur J Inflamm

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M.R. and R.E contributed equally to this workReactive oxygen species(ROS) are mainly produced by microglia and macrophages during inflammationdriven oxidative burst. However, they can in turn affect the reactivity and function ofimmune cells.For the first time, the relationship between these two key players involved in Multiple Sclerosis (MS) was evaluated at peripheral level. We performed an in-depth immune-phenotypic and functional analysis ofMBP (Myelin Basic Protein)-stimulated Peripheral Blood Mononuclear Cells (PBMCs) by flow-cytometry. In addition, blood Coenzyme-QI0 (CoQI0), total, oxidized and reduced forms of glutathione (GSTot, GSSG, GSH), malondialdehyde (MDA), ROS, anti-oxidized-low-density-lipoproteins antibodies (anti-oxLDL), and anti-oxidant-power (PAO) were studied in 31 untreated MS patients (MSnoTP), 23 MS patients (MSTP) treated with Disease Modifying Drugs (DMDs) and 39 matched controls (HC). The focus of our study was the correlation between oxidative stress biomarkers and distribution of immune-phenotypes across the 3 studied groups. In MSnoTP an inverse correlation between MDA and apoptotic cells (CD4+ AnnexinV+ TIM3+) was detected (rs= -0.50, p= 0.01). Ml functional phenotype (CDI4+ IL6+) and TH17 cells (CD4+ IL22+) inversely (rs= -0.48) and directly (rs= 0.46) correlated (p = 0.01) with Anti-oxLDL antibodies and GSSG, respectively. The latter direct correlation was shown also in MSTP. Notably, in this group, we also detected a direct correlation between CD4+ IL4+ and CD4+ IL25+ (TH2 phenotype) with CoQI0 (rs= 0.54) and GSH (rs= 0.46) (p< 0.03), two crucial anti-oxidants. Again, a direct correlation was found between CD8+ BDNF+ cells (suppressor phenotype) and anti-oxLDL (rs= 0.48, p= 0.03). Surprisingly, we measured an inverse correlation between CDI4+ ILI0+ cells (M2 immune-regulatory cells) with GSH (rs= -0.59, p< 0.001). Our findings endorse the idea of a relationship between pro-inflammatory cells and pro-oxidative environment, even at peripheral level. Interestingly, the correlation between CD4+ ILIO+ cells and a defective anti-oxidant equipment might be regarded as evidence of the involvement of these cells during an inflammatory/oxidative phase that they try to control. The finding ofthis link only in MSTP patients might suggest that DMDs can provide an alternative way to counteract inflammation, regardless of an absolute increase of these immune-regulatory cells.

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Lipid Anti-Lipid Antibody Responses Correlate with Disease Activity in Systemic Lupus Erythematosus

Cited by 15 publications

References 58 publications

Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Oxidative stress and its biomarkers in systemic lupus erythematosus

The Peripheral Network between Oxidative Stress and Inflammation in Multiple Sclerosis

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