Increase in B-cell-activation factor (BAFF) and IFN-γ productions by tonsillar mononuclear cells stimulated with deoxycytidyl-deoxyguanosine oligodeoxynucleotides (CpG-ODN) in patients with IgA nephropathy

Goto, Takashi; Bandoh, Nobuyuki; Yoshizaki, Tomoki; Nozawa, Hayabusa; Takahara, Miki; Ueda, Seigo; Hayashi, Tatsuya; Harabuchi, Yasuaki

doi:10.1016/j.clim.2007.11.003

Cited by 57 publications

(41 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tonsil in the patients with IgAN had several features, such as structural changes [27] and gene expression change [26], resulting in the change of immune response [26], [50]–[52]. Those immune changes in tonsil might allow the specific bacteria to grow in tonsil, such as these three bacteria.…”

Section: Discussionmentioning

confidence: 99%

Periodontal Disease Bacteria Specific to Tonsil in IgA Nephropathy Patients Predicts the Remission by the Treatment

et al. 2014

View full text Add to dashboard Cite

BackgroundImmunoglobulin (Ig)A nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world. Some bacteria were reported to be the candidate of the antigen or the pathogenesis of IgAN, but systematic analysis of bacterial flora in tonsil with IgAN has not been reported. Moreover, these bacteria specific to IgAN might be candidate for the indicator which can predict the remission of IgAN treated by the combination of tonsillectomy and steroid pulse.Methods and FindingsWe made a comprehensive analysis of tonsil flora in 68 IgAN patients and 28 control patients using Denaturing gradient gel electrophoresis methods. We also analyzed the relationship between several bacteria specific to the IgAN and the prognosis of the IgAN. Treponema sp. were identified in 24% IgAN patients, while in 7% control patients (P = 0.062). Haemophilus segnis were detected in 53% IgAN patients, while in 25% control patients (P = 0.012). Campylobacter rectus were identified in 49% IgAN patients, while in 14% control patients (P = 0.002). Multiple Cox proportional-hazards model revealed that Treponema sp. or Campylobactor rectus are significant for the remission of proteinuria (Hazard ratio 2.35, p = 0.019). There was significant difference in remission rates between IgAN patients with Treponema sp. and those without the bacterium (p = 0.046), and in remission rates between IgAN patients with Campylobacter rectus and those without the bacterium (p = 0.037) by Kaplan-Meier analysis. Those bacteria are well known to be related with the periodontal disease. Periodontal bacteria has known to cause immune reaction and many diseases, and also might cause IgA nephropathy.ConclusionThis insight into IgAN might be useful for diagnosis of the IgAN patients and the decision of treatment of IgAN.

show abstract

Section: Discussionmentioning

confidence: 99%

Periodontal Disease Bacteria Specific to Tonsil in IgA Nephropathy Patients Predicts the Remission by the Treatment

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Furthermore, two studies hint at a correlation between BAFF and IgAN. Specifically, serum BAFF levels were found to be weakly correlated with serum IgA levels in patients with IgAN undergoing tonsillectomy (40), and monocytes from patients with IgAN were found to produce more BAFF in response to CpG-ODN (41). An ELISA analysis of sera from 2 separate cohorts of patients with IgAN showed a modest increase in BAFF protein in cohort 1 compared with that in control samples ( Figure 8).…”

Section: Figurementioning

confidence: 99%

Mice overexpressing BAFF develop a commensal flora–dependent, IgA-associated nephropathy

McCarthy¹,

Kujawa²,

Wilson³

et al. 2011

J. Clin. Invest.

236

165

View full text Add to dashboard Cite

B cell activation factor of the TNF family (BAFF) is a potent B cell survival factor. BAFF overexpressing transgenic mice (BAFF-Tg mice) exhibit features of autoimmune disease, including B cell hyperplasia and hypergammaglobulinemia, and develop fatal nephritis with age. However, basal serum IgA levels are also elevated, suggesting that the pathology in these mice may be more complex than initially appreciated. Consistent with this, we demonstrate here that BAFF-Tg mice have mesangial deposits of IgA along with high circulating levels of polymeric IgA that is aberrantly glycosylated. Renal disease in BAFF-Tg mice was associated with IgA, because serum IgA was highly elevated in nephritic mice and BAFF-Tg mice with genetic deletion of IgA exhibited less renal pathology. The presence of commensal flora was essential for the elevated serum IgA phenotype, and, unexpectedly, commensal bacteria-reactive IgA antibodies were found in the blood. These data illustrate how excess B cell survival signaling perturbs the normal balance with the microbiota, leading to a breach in the normal mucosal-peripheral compartmentalization. Such breaches may predispose the nonmucosal system to certain immune diseases. Indeed, we found that a subset of patients with IgA nephropathy had elevated serum levels of a proliferation inducing ligand (APRIL), a cytokine related to BAFF. These parallels between BAFF-Tg mice and human IgA nephropathy may provide a new framework to explore connections between mucosal environments and renal pathology.

show abstract

“…Deterioration of renal lesions was observed after mucosal activation of DCs in the animal models of IgAN [8], and the expression of B-cell activation factor on DCs has been reported to have been significantly higher in IgAN patients than that in controls [9]. These reports indicate that DCs play key roles in the pathogenesis of IgAN.…”

Section: Introductionmentioning

confidence: 99%

Clinical and immunological implications of increase in CD208+ dendritic cells in tonsils of patients with immunoglobulin A nephropathy

Takechi

Oda

Hasegawa³

et al. 2013

Nephrology Dialysis Transplantation

View full text Add to dashboard Cite

BackgroundThe therapeutic effect of tonsillectomy for immunoglobulin A nephropathy (IgAN) has been widely recognized, but the mechanism by which tonsillar immunity leads to glomerulonephritis has been unclear. We investigated subtypes and localization of dendritic cells (DCs) in tonsils and looked for relationships between the tonsillar DCs and the clinical features and renal histological changes of patients with IgAN.MethodsWe examined tonsils from 33 IgAN patients, using as control tonsillar specimens from subjects without glomerulonephritis. Five distinct markers of DCs (CD303, CD1c, CD209, CD208 and CD1a) were analyzed by immunohistochemistry and flow cytometry. The mRNA levels of these DC markers were evaluated using real-time polymerase chain reaction. The clinical data and histological results obtained evaluating renal biopsy tissues were statistically compared with immunological data.ResultsOf the five subtypes of DCs, CD208+ DCs were significantly increased in the tonsils of IgAN patients compared with that of controls. Furthermore, the number of CD208+ DCs in the tonsils was positively and linearly correlated with the proportion of crescentic glomeruli in renal biopsy tissues and with the urinary protein level. Only few CD208+ cells, however, were found in the kidney biopsy specimens of IgAN patients.ConclusionsThese observations suggest that increased CD208+ DCs in tonsils may play a directive role in the pathogenesis of IgAN. The present results support the therapeutic significance of tonsillectomy for IgAN patients.

show abstract

Increase in B-cell-activation factor (BAFF) and IFN-γ productions by tonsillar mononuclear cells stimulated with deoxycytidyl-deoxyguanosine oligodeoxynucleotides (CpG-ODN) in patients with IgA nephropathy

Abstract: Increase in B-cell-activation factor (BAFF) and IFN-γ productions by tonsillar mononuclear cells stimulated with deoxycytidyl-deoxyguanosine oligodeoxynucleotides (CpG-ODN) in patients with IgA nephropathy

Cited by 57 publications

References 40 publications

Periodontal Disease Bacteria Specific to Tonsil in IgA Nephropathy Patients Predicts the Remission by the Treatment

Periodontal Disease Bacteria Specific to Tonsil in IgA Nephropathy Patients Predicts the Remission by the Treatment

Mice overexpressing BAFF develop a commensal flora–dependent, IgA-associated nephropathy

Clinical and immunological implications of increase in CD208+ dendritic cells in tonsils of patients with immunoglobulin A nephropathy

Contact Info

Product

Resources

About