B cells from African American lupus patients exhibit an activated phenotype

Ménard, Laurence; Habte, Sium; Gonsiorek, Waldemar; Lee, Dong Hoon; Banas, Dana; Holloway, Deborah A.; Manjarrez‐Orduño, Nataly; Cunningham, Mark D.; Stetsko, Dawn K.; Casano, Francesca; Kansal, Selena; Davis, Patricia M.; Carman, Julie A.; Zhang, Clarence K.; Abidi, Ferva; Furie, Richard; Nadler, Steven G.; Suchard, Suzanne J.

doi:10.1172/jci.insight.87310

Cited by 44 publications

(42 citation statements)

References 47 publications

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“…When considering our findings specific to African-American SLE, there is an interesting recent report supporting an activated B cell phenotype in African-American patients with SLE as compared with European-American patients with SLE. 15 Menard et al recently showed a distinct memory B cell subset expansion (double negative B cells: CD19+ IgD− CD27− and activated B cells expressing high levels of CD80, CD86, PD-1 and CD40L) in African-American but not European-American patients with SLE. 15 As in other studies, we find that the baseline level of type I IFN activity is significantly higher in African-American patients ( table 1 ).…”

Section: Discussionmentioning

confidence: 99%

“… 15 Menard et al recently showed a distinct memory B cell subset expansion (double negative B cells: CD19+ IgD− CD27− and activated B cells expressing high levels of CD80, CD86, PD-1 and CD40L) in African-American but not European-American patients with SLE. 15 As in other studies, we find that the baseline level of type I IFN activity is significantly higher in African-American patients ( table 1 ). It is possible that both intrinsic B cell factors and increased exposure to type I IFNs result in this B cell activation observed in African-American patients.…”

Section: Discussionmentioning

confidence: 99%

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Associations between type I interferon and antiphospholipid antibody status differ between ancestral backgrounds

et al. 2018

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ObjectiveThe type I interferon pathway is activated in many patients with systemic lupus erythematosus (SLE), and anti-double-stranded DNA (dsDNA) and anti-RNA binding protein autoantibodies are correlated with high interferon-α (IFNα) activity. We studied whether antiphospholipid (APL) antibodies, which should not stimulate Toll-like receptors, are also associated with high levels of IFNα activity.MethodsSerum IFNα activity was measured in patients with SLE using the WISH cell bioassay. IgG APL, anti-RBP and anti-dsDNA antibodies were measured in the clinical laboratory, and standard clinical cut-offs were used to define the positive results.ResultsHigh IFNα activity was associated with anti-RBP and anti-dsDNA antibodies in all three ancestral backgrounds. Strikingly, African-American subjects with a positive APL antibody test had higher IFNα activity than those without IgG APL antibodies. This was not shared with other ancestral backgrounds. This finding was independent of other autoantibody profiles, and clinical features did not differ between IgG APL antibody positive versus negative African-American patients.ConclusionThe difference in association between IFNα activity and IgG APL status between ancestral backgrounds supports differences in molecular pathogenesis. This may suggest B cell hyperactivity in the setting of type I IFN in African-Americans and could suggest ways to individualise therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Associations between type I interferon and antiphospholipid antibody status differ between ancestral backgrounds

et al. 2018

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“…SLE is characterized by complement activation, autoantibody production, immune complex deposition and systemic inflammation [1,2]. Previous studies have shown that immunological abnormalities may contribute to the development of SLE, including cytokine disorders and T and B cell activation [5,6]. Previous studies have shown that immunological abnormalities may contribute to the development of SLE, including cytokine disorders and T and B cell activation [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…Approximately 17-48/100 000 people worldwide suffer from SLE, and lupus could damage their immune system by the direct action of antibodies that influence physical and mental health, as well as quality of life and life expectancy in patients [3,4]. Previous studies have shown that immunological abnormalities may contribute to the development of SLE, including cytokine disorders and T and B cell activation [5,6]. However, until now, the particular aetiology and pathogenesis of SLE have not been elucidated clearly.…”

Section: Introductionmentioning

confidence: 99%

Association of interleukin 22 gene polymorphisms and serum IL-22 level with risk of systemic lupus erythematosus in a Chinese population

Wang

Zeng

Qin

et al. 2018

Clinical and Experimental Immunology

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The aim of this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) of the interleukin 22 (IL-22) gene and systemic lupus erythematosus (SLE) in a Chinese population. Three IL-22 SNPs (rs2227485, rs2227513 and rs2227491) were genotyped using SNaPshot SNP genotyping assays and identified by sequencing in 314 SLE patients and 411 healthy controls. The IL-22 level of serum was assessed by enzyme-linked immunosorbent assay (ELISA) kits. Data were analysed by spss version 17.0 software. We found that rs2227513 was associated with an increased risk of SLE [AG versus AA: adjusted odds ratio (aOR) = 2·24, 95% confidence interval (CI) = 1·22-4·12, P = 0·010; G versus· A: adjusted OR = 2·18, 95% CI = 1·20-3·97, P = 0·011]. Further analysis in patients with SLE showed that the AG genotype and G allele were associated with an increased risk of renal disorder in SLE (G versus A: aOR = 3·09, 95% CI = 1·30-7·33, P = 0·011; AG versus· AA: aOR = 3·25, 95% CI = 1·35-7·85, P = 0·009). In addition, the concentration of IL-22 was significantly lower in the rs2227513 AG genotype compared with AA genotype (P = 0·028). These results suggest that rs2227513 polymorphism might contribute to SLE susceptibility, probably by decreasing the expression of IL-22.

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“…+ and CD27 + B-cell subsets in the peripheral blood of patients with SLE are of high significance (21,22), the present study assessed the expression of these B-cell subsets by flow cytometry. The results revealed that the proportion of CD27 + B-cells was increased, while that of CD19 + B cells was decreased after addition of LPS.…”

Section: Effects Of Four Gs Monomers On B-cell Subsets As the Propormentioning

confidence: 99%

Regulatory effects of four ginsenoside monomers in humoral immunity of systemic lupus erythematosus

Zhang

Lin

et al. 2017

Exp Ther Med

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Abstract. Ginsenosides Rb1, Rh1, Rg1 and Rg3 are known as the main active components extracted from the roots of the Panax ginseng C.A. Meyer, and were reported to have immunoregulatory effects. Disruption of B-cell immune regulation during the pathogenesis of systemic lupus erythematosus (SLE) may lead to the production of large amounts of antibodies. The present study investigated the effects of the four ginsenoside monomers on B-cell immune regulation and observed that they inhibited the proliferation and secretion of B cells induced by LPS, caused an upregulation of the expression of apoptosis-associated proteins Fas/Fas ligand and caspase-3, the expression of FcγRIIB (CD32) as well as the proportion of inactive B cells (CD19 + CD27 -). These results indicate that Rb1, Rh1, Rg1 and Rg3 inhibit the humoral immunity of SLE, among which Rh1 exhibited the most obvious inhibitory effect.

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B cells from African American lupus patients exhibit an activated phenotype

Cited by 44 publications

References 47 publications

Associations between type I interferon and antiphospholipid antibody status differ between ancestral backgrounds

Associations between type I interferon and antiphospholipid antibody status differ between ancestral backgrounds

Association of interleukin 22 gene polymorphisms and serum IL-22 level with risk of systemic lupus erythematosus in a Chinese population

Regulatory effects of four ginsenoside monomers in humoral immunity of systemic lupus erythematosus

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