The anti-DNA antibody: origin and impact, dogmas and controversies

Rekvig, Ole Petter

doi:10.1038/nrrheum.2015.69

Cited by 73 publications

(135 citation statements)

References 118 publications

(186 reference statements)

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“…Because B-cell response to nuclear auto-antigens requires T-cell help, formation of pathogenic autoantibodies in SLE (e.g. anti-dsDNA) follows the same rules [11]. As a consequence, in all SLE patients a pool of autoreactive memory B-and T-cells is steadily generated.…”

Section: Introductionmentioning

confidence: 97%

Changes of memory B- and T-cell subsets in lupus nephritis patients

Kosałka

Jakieła

Musiał

2015

Folia Histochem Cytobiol.

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Introduction. Renal involvement in systemic lupus erythematosus (SLE) is associated with production of antibodies to double stranded DNA, deposition of immune complexes and organ damage. These processes have been linked with abnormalities in B-and T-cell memory compartments. The aim of the study was to analyze subsets of peripheral memory B-cells and T-cells in lupus nephritis (LN) patients. Material and methods. We used multicolor flow cytometry to analyze major memory subsets of peripheral blood B-cells (defined by CD27, IgD and CD21) and T-cells (CD45RA, CD45RO, CCR7) in 32 patients with active or inactive LN, and 23 control subjects. Results. Lupus nephritis patients were characterized by increased percentage of immature/early-transitional B-cells (CD27-IgD+CD21-), higher frequency of activated switched memory (SM, CD27+IgD-CD21-) and exhausted memory B-cells (CD27-IgD-), and decrease in non-switched memory (NSM, CD27+IgD+) B-cells. CD21 low subsets (immature and activated B-cells) were particularly expanded in patients with active disease. In both groups of LN patients we observed decline in the absolute count of NSM B-cells. It was paralleled by lymphopenia in naïve CD4+ T-cell compartment and increase in the frequency of effector memory T-cells, and these changes were more pronounced in active LN. Conclusions. B-cell memory compartment in LN is deficient in NSM cells and during active disease it is further skewed towards SM and exhausted memory phenotypes, most likely as a cause of chronic antigenic stimulation. Parallel changes in T-helper cell subsets suggest a similar mechanism of SLE-related lymphopenia for both B-cell and T-cell compartment.

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Section: Introductionmentioning

confidence: 97%

Changes of memory B- and T-cell subsets in lupus nephritis patients

Kosałka

Jakieła

Musiał

2015

Folia Histochem Cytobiol.

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“…Alternatively, these antibodies may bind to DNA, nucleosomes, or cross-reacting antigens already present in the target organ and then trigger a similar cascade of pathological events [3,32,33].…”

Section: B Cell Targeting Agents Abetimus Sodiummentioning

confidence: 98%

Update on Biologic Therapies for Systemic Lupus Erythematosus

et al. 2016

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Systemic lupus erythematosus (SLE) is a chronic multisystemic autoimmune disease driven by genetic, hormonal, and environmental factors. Despite the advances in diagnostic and therapeutic approaches in the last decades, SLE still leads to significant morbidity and increased mortality. Although a cure for SLE is still unknown, treatment is required to control acute disease exacerbation episodes (flares), decrease the frequency and severity of subsequent lupus flares, address comorbidities, and prevent end-organ damage. While conventional SLE pharmacotherapy may exhibit suboptimal efficacy and substantial toxicity, a growing knowledge of the disease pathogenesis enabled the research on novel therapeutic agents directed at specific disease-related targets. In this paper, we review the recent progress in the clinical investigation of biologic agents targeting B cells, T cells, cytokines, innate immunity, and other immunologic or inflammatory pathways. Although many investigational agents exhibited insufficient efficacy or inadequate safety in clinical trials, one of them, belimumab, fulfilled the efficacy and safety regulatory requirements and was approved for the treatment of SLE in Europe and the USA, which confirms that, despite all difficulties, advances in this field are possible.

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“…infections, 11e14 as reviewed by Rekvig. 15 Approximately two decades later, they were described in the autoimmune syndrome SLE. 16e19 Since then, their role in SLE, rather than in infections and malignancies, 15 has been extensively studied in two contexts: diagnostics and pathogenicity.…”

Section: Pathogenesisdbackground and Present Statusmentioning

confidence: 99%

Future Perspectives on Pathogenesis of Lupus Nephritis

Rekvig

Thiyagarajan

Pedersen

et al. 2016

The American Journal of Pathology

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Divergent incommensurable models have been developed to explain the pathogenesis of lupus nephritis. Most contemporary models favor a central role for anti-chromatin antibodies. How they exert their pathogenic effect has, however, endorsed conflicts that at least for now preclude insight into definitive pathogenic pathways. The following paradigms are contemporarily in conflict with each other: i) the impact of anti-double-stranded DNA (dsDNA) antibodies that cross-react with inherent renal antigens, ii) the impact of anti-dsDNA antibodies targeting exposed chromatin in glomeruli, and iii) the impact of relative antibody avidity for dsDNA, chromatin fragments, or cross-reacting antigens. Aside from these three themes, the pathogenic role of T cells in lupus nephritis is not clear. These different models should be tested through a collaboration between scientists belonging to the different paradigms. If it turns out that there are different pathogenic pathways in lupus nephritis, the emerging pathogenic mechanism(s) may be encountered with new individual causal therapy modalities. Today, therapy is still unspecific and far from interfering with the cause(s) of the disorder. This review attempts to describe what we know about processes that may cause lupus nephritis and how such basic processes may be affected if we can specifically interrupt them. Secondary inflammatory mechanisms, cytokine signatures, activation of complement, and other contributors to inflammation will not be discussed herein; rather, the events that trigger these factors will be discussed.

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The anti-DNA antibody: origin and impact, dogmas and controversies

Cited by 73 publications

References 118 publications

Changes of memory B- and T-cell subsets in lupus nephritis patients

Changes of memory B- and T-cell subsets in lupus nephritis patients

Update on Biologic Therapies for Systemic Lupus Erythematosus

Future Perspectives on Pathogenesis of Lupus Nephritis

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