Autoantibodies that bind glomeruli: Cross‐reactivity with bacterial antigen

Chowdhry, Iftikhar A.; Kowal, Czeslawa; Hardin, John A.; Zhou, Zhijie; Diamond, Betty

doi:10.1002/art.21143

Cited by 11 publications

(7 citation statements)

References 40 publications

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“…A first subpopulation would be associated with dsDNA, a second would be trapped by negatively charged molecules (the latter cross‐reacting with glomerular antigens), and a third would be sequestered by virtue of their genuine specificity for local antigens. The report that non–DNA‐binding antibodies recognize the same renal antigens as DNA‐binding antibodies (44) is compatible with our view that cross‐reactivity of anti‐dsDNA antibodies with kidney antigens determines their renal pathogenicity.…”

Section: Discussionsupporting

confidence: 86%

Association of α‐actinin–binding anti–double‐stranded DNA antibodies with lupus nephritis

Renaudineau

Croquefer

Jousse

et al. 2006

Arthritis & Rheumatism

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Objective. Anti-double-stranded DNA (antidsDNA) antibodies may contribute to the pathogenesis of glomerulonephritis (GN) by cross-reacting with ␣-actinin in murine models and in some patients with systemic lupus erythematosus (SLE). We therefore sought to determine possible disease associations with serologic and clinical features and to characterize this new autoantibody specificity.Methods. One hundred patients with SLE were recruited into this multicenter study, as well as 100 rheumatic disease controls and 2,100 healthy blood donors. Clinical disease was evaluated by the SLE Disease Activity Index (SLEDAI; excluding the anti-DNA component). Anti-dsDNA antibodies were detected by conventional enzyme-linked immunosorbent assay (ELISA) and by a commercial enzyme immunoassay (EIA). Anti-␣-actinin antibodies were detected by ELISA, and their specificity was confirmed by Western blotting and by indirect immunofluorescence using rat kidney sections and mesangial cells as substrates. Highly positive sera were selected for absorption experiments and were affinity-purified for cross-reactivity studies and measurement of antibody avidity.Results. Sera from 62 of the SLE patients had anti-dsDNA antibodies; 21 of these sera also had anti-␣-actinin antibodies, as compared with 1 of the 38 sera without anti-dsDNA antibodies. Of the 22 patients with anti-␣-actinin antibodies, 10 had GN, as compared with 14 of the 78 without anti-␣-actinin antibodies (P < 0.01). In patients with GN, anti-␣-actinin, but not anti-dsDNA, antibodies correlated with the SLEDAI score (minus the anti-DNA component) and with treatment. The fraction of serum anti-dsDNA antibodies that cross-reacted with ␣-actinin exhibited high avidity for dsDNA, as determined using a commercial EIA for high-avidity anti-dsDNA antibodies and an in-house conventional ELISA.Conclusion. The ␣-actinin-binding antibodies are significantly associated with GN in SLE. Whether such autoantibodies may anticipate the development of this complication of SLE remains to be verified.

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Section: Discussionsupporting

confidence: 86%

Association of α‐actinin–binding anti–double‐stranded DNA antibodies with lupus nephritis

Renaudineau

Croquefer

Jousse

et al. 2006

Arthritis & Rheumatism

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“…IgG antibodies to dsDNA used to be considered the most important antibody in SLE, especially with glomerulonephritis (54,55). However, in lupus patients, only 50% of antibodies eluted from glomeruli bound DNA (56). In our model, increased IgG deposition in glomeruli of apoE 2/2 Fas 2/2 mice with increased IgG anti-POVPC and anti-PGPC (Figs.…”

Section: Fasmentioning

confidence: 59%

ApoE−/−Fas−/− C57BL/6 mice: a novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia

Feng

Liu

Rumbin

et al. 2007

Journal of Lipid Research

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To establish a mouse model of accelerated atherosclerosis in lupus, we generated apolipoprotein E-deficient (apoE 2/2 ) and Fas lpr/lpr (Fas 2/2 ) C57BL/6 mice. On a normal chow diet, 5 month old apoE 2/2 Fas 2/2 mice had enlarged glomerular tuft areas, severe proteinuria, increased circulating autoantibody levels, and increased apoptotic cells in renal and vascular lesions compared with either single knockout mice. Also, double knockout mice developed increased atherosclerotic lesions but decreased serum levels of total and non-HDL cholesterol compared with apoE Cardiovascular complications related to atherosclerosis are common among patients with systemic lupus erythematosus (SLE) and contribute to their disability and death (1-4). Women with SLE between 35 and 44 years old have an estimated 50-fold increased risk of myocardial infarction compared with age-and gender-matched controls (5). After controlling for traditional Framingham risk factors, the relative risk for early coronary heart disease attributed to SLE itself is 7.5-fold (6). An increased prevalence of subclinical atherosclerosis in SLE has also been established: 37% of SLE patients versus 15% of controls have plaques detectable by carotid artery ultrasound (3), and 31% of SLE patients versus 9% of controls exhibit coronary artery calcification (4). The disease processes of SLE itself, including a longer duration of disease, a higher damage-index score, and less aggressive immunosuppressive therapy, are independent risk factors for atherosclerosis (3).Similar to accelerated atherosclerosis in SLE, bone loss in SLE involves both traditional osteoporosis risk factors and lupus-related factors. More than one-third of SLE patients were osteopenic by bone mineral density (BMD) scanning (7,8) More strikingly, at least 20% of SLE patients (mean age of 41 years) had osteoporotic vertebral

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“…Further investigations revealed that in total eight antibodies either reacting with pneumococcal saccharide or DNA were able to bind glomerular structures. Of these, six bound to renal protein antigens which had previously been described to be cross-reactive with DNA, whereas the remaining two bound to histones [ 76 ]. Effects of two additional bacteria could be shown more recently.…”

Section: Resultsmentioning

confidence: 99%

The Influence and Role of Microbial Factors in Autoimmune Kidney Diseases: A Systematic Review

Kronbichler

Kerschbaum

Mayer

2015

Journal of Immunology Research

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A better understanding of the pathophysiology of autoimmune disorders is desired to allow tailored interventions. Despite increased scientific interest a direct pathogenic factor in autoimmune renal disease has been described only in a minority like membranous nephropathy or ANCA-associated vasculitis. Nonetheless the initial step leading to the formation of these antibodies is still obscure. In this review we will focus on the possible role of microbial factors in this context. Staphylococcus aureus may be a direct pathogenetic factor in granulomatosis with polyangiitis (GPA). Chronic bacterial colonization or chronic infections of the upper respiratory tract have been proposed as trigger of IgA vasculitis and IgA nephropathy. Interventions to remove major lymphoid organs, such as tonsillectomy, have shown conflicting results but may be an option in IgA vasculitis. Interestingly no clear clinical benefit despite similar local colonization with bacterial strains has been detected in patients with IgA nephropathy. In systemic lupus erythematosus injection of bacterial lipopolysaccharide induced progressive lupus nephritis in mouse models. The aim of this review is to discuss and summarize the knowledge of microbial antigens in autoimmune renal disease. Novel methods may provide insight into the involvement of microbial antigens in the onset, progression, and prognosis of autoimmune kidney disorders.

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Autoantibodies that bind glomeruli: Cross‐reactivity with bacterial antigen

Cited by 11 publications

References 40 publications

Association of α‐actinin–binding anti–double‐stranded DNA antibodies with lupus nephritis

Association of α‐actinin–binding anti–double‐stranded DNA antibodies with lupus nephritis

ApoE−/−Fas−/− C57BL/6 mice: a novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia

The Influence and Role of Microbial Factors in Autoimmune Kidney Diseases: A Systematic Review

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