Aberrantly Glycosylated IgA1 in Glomerular Immune Deposits of IgA Nephropathy

Giannakakis, Konstantinos; Feriozzi, Sandro; Perez, Marie; Faraggiana, Tullio; Muda, Andrea Onetti

doi:10.1681/asn.2007030259

Cited by 38 publications

(33 citation statements)

References 33 publications

(29 reference statements)

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“…Thereafter, aberrantly glycosylated IgA1 produced as a result of the anomalous stimulated immune response in the bone marrow is deposited within the mesangial area. Such deposition correlates with the severity of glomerular IgAN lesions in situ (21). Tonsillectomy might act upstream of the pathogenic mechanism by eliminating antigenic stimuli from the tonsillar mucosa, whereas steroid pulse therapy acts downstream of the mechanism by suppressing the abnormal immune response in the bone marrow and leading to subsequent inflammation in renal glomeruli.…”

Section: Discussionmentioning

confidence: 99%

Effect of Tonsillectomy Plus Steroid Pulse Therapy on Clinical Remission of IgA Nephropathy

Komatsu

Fujimoto²,

Hara³

et al. 2008

Clinical Journal of the American Society of Nephrology

122

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Background and objectives: Few well-designed investigations have examined how tonsillectomy plus steroid pulse therapy affects IgA nephropathy. A prospective, controlled study therefore was performed to compare the effects of combined therapy with those of steroid pulse alone in patients with IgA nephropathy.Design, setting, participants, & measurements: Fifty-five patients were followed up for 54.0 ؎ 21.2 mo. Thirty-five of them underwent tonsillectomy and steroid pulse therapy (group C), and 20 received steroid pulse monotherapy (group M). Both groups received methylprednisolone intravenously, followed by oral prednisolone (initial dosage 0.5 mg/kg per d) for 12 to 18 mo. Primary evaluation items were a 100% increase in serum creatinine from baseline levels or the disappearance of urinary protein (UP) and/or occult blood (UOB) indicating clinical remission.Results: At 24 mo after the initial treatment, the ratios of the UP and UOB disappearance were higher in group C than in group M, and the therapeutic effect persisted until the final observation. None of group C achieved a 100% increase in serum creatinine from the baseline level, whereas one patient in group M developed ESRD during the observation period. The histologic findings of repeated biopsy specimens from 18 patients revealed that mesangial proliferation and IgA deposition were significantly more reduced in group C than in group M. The Cox regression model showed that the combined therapy was approximately six-fold more effective in causing the disappearance of UP than steroid pulse monotherapy.Conclusion: Tonsillectomy combined with steroid pulse treatment can induce clinical remission in patients with IgA nephropathy.

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Section: Discussionmentioning

confidence: 99%

Effect of Tonsillectomy Plus Steroid Pulse Therapy on Clinical Remission of IgA Nephropathy

Komatsu

Fujimoto²,

Hara³

et al. 2008

Clinical Journal of the American Society of Nephrology

122

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“…The patient developed initial signs and symptoms of 35 glomerulonephritis at the age of 9 years but presented again at the age of 14 years with weight 36 gain, renal failure, nephrotic-range proteinuria and malignant hypertension. IgA1 and complement proteins [10,17]. Complement components deposit mainly in the 53 mesangium and include C3, C4d, C4-binding protein, factor H, mannose-binding lectin, C5b-54 9 and properdin [1,7,8,13,15,17,20 Factor H is deposited in the kidneys during IgAN [1].…”

Section: Abstract 28mentioning

confidence: 99%

IgA nephropathy associated with a novel N-terminal mutation in factor H

et al. 2010

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28Most patients with IgA nephropathy exhibit complement deposition in the glomerular 29 mesangium. Certain cases of IgA nephropathy have been associated with reduced levels of 30 factor H. A recent study could not demonstrate mutations at the C terminal of factor H. We 31 describe a novel heterozygous mutation in factor H, position A48S (nucleotide position 142 32 G>T, alanine>serine), detected in exon 2 of a 14 year old girl with IgA nephropathy. The 33 patient exhibited reduced levels of C3 and factor H, the latter suggesting that the mutation 34 affected factor H secretion. The patient developed initial signs and symptoms of 35 glomerulonephritis at the age of 9 years but presented again at the age of 14 years with weight 36 gain, renal failure, nephrotic-range proteinuria and malignant hypertension.

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“…The following processes are involved in the pathogenesis (7) of IgAN: aberrant glycosylation of IgA1 (8), synthesis of antibodies directed against galactosedeficient IgA1, binding of the galactose-deficient IgA1 by antibodies to form immune complexes, and deposition of these complexes in the glomerular mesangium, inducing activation of mesangial cells and glomerular damage (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Association of C4d Deposition with Clinical Outcomes in IgA Nephropathy

Espinosa¹,

Ortega²,

Sánchez³

et al. 2014

Clinical Journal of the American Society of Nephrology

177

162

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Background and objectives Several studies have suggested that activation of the complement system is a contributing pathogenic mechanism in IgA nephropathy (IgAN). C4d staining is an inexpensive and easy-toperform method for the analysis of renal biopsies. This study aimed to assess the clinical and prognostic implications of C4d staining in IgAN.Design, setting, participants, & measurements This retrospective cohort study included 283 patients with IgAN in 11 hospitals in Spain who underwent a renal biopsy between 1979 and 2010. The primary predictor was mesangial C4d staining. Secondary predictors included demographic, clinical, and laboratory characteristics, and Oxford pathologic classification criteria. The primary end point was the cumulative percentage of patients who developed ESRD, defined as onset of chronic dialysis or renal transplantation. C4d was analyzed by immunohistochemical staining using a polyclonal antibody. Kaplan-Meier and Cox proportional hazards analyses were performed to evaluate the effect of C4d staining on renal survival.Results There were 109 patients (38.5%) and 174 patients (61.5%) who were classified as C4d positive and C4d negative, respectively. Renal survival at 20 years was 28% in C4d-positive patients versus 85% in C4d-negative patients (P,0.001). Independent risk factors associated with ESRD were as follows: proteinuria (hazard ratio [HR] per every 1 g/d increase. 1.16; 95% confidence interval [95% CI], 1.03 to 1.31; P=0.01), eGFR (HR per every 1 ml/min per 1.73 m 2 increase, 0.96; 95% CI, 0.94 to 0.97; P,0.001), T2 Oxford classification (tubular atrophy/ interstitial fibrosis, .50%; HR, 4.42; 95% CI, 1.40 to 13.88; P=0.01), and C4d-positive staining (HR, 2.45; 95% CI, 1.30 to 4.64; P=0.01).Conclusions C4d-positive staining is an independent risk factor for the development of ESRD in IgAN. This finding is consistent with the possibility that complement activation is involved in the pathogenesis of this disease.

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Aberrantly Glycosylated IgA1 in Glomerular Immune Deposits of IgA Nephropathy

Cited by 38 publications

References 33 publications

Effect of Tonsillectomy Plus Steroid Pulse Therapy on Clinical Remission of IgA Nephropathy

Effect of Tonsillectomy Plus Steroid Pulse Therapy on Clinical Remission of IgA Nephropathy

IgA nephropathy associated with a novel N-terminal mutation in factor H

Association of C4d Deposition with Clinical Outcomes in IgA Nephropathy

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