Lupus nephritis: A critical review

Borchers, Andrea T.; Leibushor, Naama; Naguwa, Stanley M.; Cheema, Gurtej S.; Shoenfeld, Yehuda; Gershwin, M. Eric

doi:10.1016/j.autrev.2012.08.018

Cited by 211 publications

(166 citation statements)

References 350 publications

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“…Lupus nephritis (LN) develops in ~50% SLE patients, representing the main cause of morbidity and mortality [1,2]. The significance of self-reacting B-cells in the pathogenesis of LN is supported by a strong causal link between autoantibodies against double stranded DNA (dsDNA) and renal involvement [3,4].…”

Section: Introductionmentioning

confidence: 99%

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: 99%

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

Kosałka

Jakieła

Musiał

2015

Folia Histochem Cytobiol.

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“…There is a consensus about an autoantibody genesis of LN 2-5 mainly deriving from experimental models, but the mechanisms leading to the formation of immune deposits and the development of renal lesions are not clarified. 6 Three categories of autoantibodies have been identified that constitute the basis for any pathologic and clinical consideration. The first category targets implanted antigens (DNA, histones, and nucleosomes), [7][8][9][10] mainly deriving from breakdown of apopotic cells.…”

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confidence: 99%

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2)

Bruschi¹,

Galetti

Sinico

et al. 2015

Journal of the American Society of Nephrology

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Glomerular planted antigens (histones, DNA, and C1q) are potential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patients with LN. Prevalent antibody isotypes were defined, levels were determined, and glomerular colocalization was investigated. Renal and circulating antibodies were matched, and serum levels were compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (anti-a-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including antia-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and anti-a-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria.3.5 g/24 hours and creatinine.1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis.

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“…This infiltration includes T cells, B cells, neutrophils, and mononuclear phagocytes, and involves the glomerular as well as the tubulointerstitial compartments of the kidney (6,7). Infiltrating leukocytes constitute a source of inflammatory and profibrotic mediators (e.g., cytokines, chemokines, extracellular matrix proteins), which contribute to the proliferation and differentiation of resident kidney cells and to matrix deposition leading to renal injury (7)(8)(9)(10). Thus, preventing or reducing leukocyte recruitment into inflamed kidneys should inhibit the progression of lupus nephritis.…”

mentioning

confidence: 99%

CCR1 Inhibition Ameliorates the Progression of Lupus Nephritis in NZB/W Mice

Bignon

Gaudin

Hémon

et al. 2014

The Journal of Immunology

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Systemic lupus erythematosus is a chronic inflammatory autoimmune disease, the development of which is characterized by a progressive loss of renal function. Such dysfunction is associated with leukocyte infiltration in the glomerular and tubulointerstitial compartments in both human and experimental lupus nephritis. In this study, we investigated the role of the Ccr1 chemokine receptor in this infiltration process during the progression of nephritis in the lupus-prone New Zealand Black/New Zealand White (NZB/W) mouse model. We found that peripheral T cells, mononuclear phagocytes, and neutrophils, but not B cells, from nephritic NZB/W mice were more responsive to Ccr1 ligands than the leukocytes from younger prenephritic NZB/W mice. Short-term treatment of nephritic NZB/W mice with the orally available Ccr1 antagonist BL5923 decreased renal infiltration by T cells and macrophages. Longer Ccr1 blockade decreased kidney accumulation of effector/memory CD4+ T cells, Ly6C+ monocytes, and both M1 and M2 macrophages; reduced tubulointerstitial and glomerular injuries; delayed fatal proteinuria; and prolonged animal lifespan. In contrast, renal humoral immunity was unaffected in BL5923-treated mice, which reflected the unchanged numbers of infiltrated B cells in the kidneys. Altogether, these findings define a pivotal role for Ccr1 in the recruitment of T and mononuclear phagocyte cells to inflamed kidneys of NZB/W mice, which in turn contribute to the progression of renal injury.

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Lupus nephritis: A critical review

Cited by 211 publications

References 350 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

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2)

CCR1 Inhibition Ameliorates the Progression of Lupus Nephritis in NZB/W Mice

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