Anti-ribosomal P antibodies and lupus nephritis

Hirohata, Shunsei

doi:10.1007/s10157-011-0462-9

Cited by 19 publications

(10 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be pointed out that anti-ribosomal P enhances the capacity of activated human monocytes to produce IL-6, TNF-α and vascular endothelial growth factor [29,30], which can alter the integrity of the BBB [31-34]. However, neither serum anti-NR2 nor serum anti-ribosomal P was correlated with Q albumin in our series of patients (data not shown).…”

Section: Discussionmentioning

confidence: 61%

Blood-brain barrier damages and intrathecal synthesis of anti-N-methyl-D-aspartate receptor NR2 antibodies in diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus

et al. 2014

Self Cite

View full text Add to dashboard Cite

IntroductionAlthough neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the recalcitrant complications of the disease, its pathogenesis still remains unclear. Previous studies revealed that antibodies reactive with NMDA (N-methyl-D-aspartate) receptor NR2 (anti-NR2) are elevated in cerebrospinal fluid (CSF) of patients with diffuse psychiatric/neuropsychological syndromes (diffuse NPSLE), which is usually more recalcitrant than neurologic syndromes of NPSLE (focal NPSLE). Two mechanisms have been implicated for the elevation of CSF IgG, including intrathecal synthesis and transudation through the damaged blood-brain barrier (BBB). The present study was designed in order to elucidate the roles of BBB function and intrathecal synthesis of anti-NR2 in the elevation of CSF anti-NR2 with regard to the severity in NPSLE.MethodsPaired serum and CSF samples were obtained from 81 systemic lupus erythematosus (SLE) patients when they presented active neuropsychiatric manifestations, and from 22 non-SLE control patients with non-inflammatory neurological diseases. The 81 SLE patients consisted of 55 patients with diffuse NPSLE, including 23 patients with acute confusional state (ACS), the severest form of diffuse NPSLE, and 26 patients with neurologic syndromes or peripheral nervous system involvement (focal NPSLE). IgG anti-NR2 and albumin were measured by ELISA. BBB function and intrathecal synthesis of anti-NR2 were evaluated by Q albumin and by CSF anti-NR2 index, respectively.ResultsCSF anti-NR2 levels, Q albumin and CSF anti-NR2 index were significantly higher in NPSLE than in non-SLE control. CSF anti-NR2 levels and Q albumin were significantly higher in ACS than in non-ACS diffuse NPSLE (anxiety disorder, cognitive dysfunction, mood disorder and psychosis) or in focal NPSLE, whereas there was no significant difference in CSF anti-NR2 index among the 3 groups. CSF anti-NR2 levels were significantly correlated with Q albumin in diffuse NPSLE (r = 0.3754, P = 0.0053).ConclusionsThese results demonstrate that the severity of BBB damages plays a crucial role in the development of ACS, the severest form of diffuse NPSLE, through the accelerated entry of larger amounts of anti-NR2 into the central nervous system.

show abstract

Section: Discussionmentioning

confidence: 61%

Blood-brain barrier damages and intrathecal synthesis of anti-N-methyl-D-aspartate receptor NR2 antibodies in diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…The DNA–histone complexes binding to purified cell-penetrating antibodies extracellularly can significantly enhance their subsequent cell entry depending on the environment (70). Besides, a wide variety of cognate nuclear antigens can function as endocytic receptors and promote subsequent internalization of antibodies into the cell, e.g., ribosomal P proteins (37), C1q (36), annexin II (30), α-actinin (38), and heparan sulfate (35, 46), further confirmed that the antigen-antibody mediation is crucial for the penetration mechanism. Although it is still unclear how anti-dsDNA antibodies actually cross the cell membrane, these data provide novel insights into antibody-binding endocytic receptors and elucidate their pathogenic role in SLE.…”

Section: The Pathogenicity Of Anti-dsdna Antibodiesmentioning

confidence: 81%

Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies

2019

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is characterized by high-titer serological autoantibodies, including antibodies that bind to double-stranded DNA (dsDNA). The origin, specificity, and pathogenicity of anti-dsDNA antibodies have been studied from a wider perspective. These autoantibodies have been suggested to contribute to multiple end-organ injuries, especially to lupus nephritis, in patients with SLE. Moreover, serum levels of anti-DNA antibodies fluctuate with disease activity in patients with SLE. By directly binding to self-antigens or indirectly forming immune complexes, anti-dsDNA antibodies can accumulate in the glomerular and tubular basement membrane. These autoantibodies can also trigger the complement cascade, penetrate into living cells, modulate gene expression, and even induce profibrotic phenotypes of renal cells. In addition, the expression of suppressor of cytokine signaling 1 is reduced by anti-DNA antibodies simultaneously with upregulation of profibrotic genes. Anti-dsDNA antibodies may even participate in the pathogenesis of SLE by catalyzing hydrolysis of certain DNA molecules or peptides in cells. Recently, anti-dsDNA antibodies have been explored in greater depth as a therapeutic target in the management of SLE. A substantial amount of data indicates that blockade of pathogenic anti-dsDNA antibodies can prevent or even reverse organ damage in murine models of SLE. This review focuses on the recent research advances regarding the origin, specificity, classification, and pathogenicity of anti-dsDNA antibodies and highlights the emerging therapies associated with them.

show abstract

“…57–59 While space constraints prevent a more detailed treatment of this topic, it is important to point out, as mentioned earlier, that elution studies from LN kidneys showed that anti-dsDNA Ab only account for 10%–20% of kidney deposited IgG overall. 60 Hence, IgG not recognizing DNA represents the majority of nephritogenic Ab.…”

mentioning

confidence: 99%

The Role of Anti-DNA Antibodies in the Development of Lupus Nephritis: A Complementary, or Alternative, Viewpoint?

Goilav

Putterman

2015

Seminars in Nephrology

View full text Add to dashboard Cite

Anti-ribosomal P antibodies and lupus nephritis

Cited by 19 publications

References 45 publications

Blood-brain barrier damages and intrathecal synthesis of anti-N-methyl-D-aspartate receptor NR2 antibodies in diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus

Blood-brain barrier damages and intrathecal synthesis of anti-N-methyl-D-aspartate receptor NR2 antibodies in diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus

Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies

The Role of Anti-DNA Antibodies in the Development of Lupus Nephritis: A Complementary, or Alternative, Viewpoint?

Contact Info

Product

Resources

About