The Abundance of Antigalactose-deficient IgA1 Autoantibodies Results in Glomerular Deposition and IgA Nephropathy Recurrence After Renal Transplantation

Nakamura, Tsukasa; Shirouzu, Takayuki; Harada, S.; Sugimoto, Ryusuke; Nobori, Shuji; Yoshikawa, Mikiko; Ushigome, Hidetaka; Kawai, Shintaro

doi:10.1097/tp.0000000000003879

Cited by 5 publications

(6 citation statements)

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“…Importantly, atacicept treatment led to dose-dependent reductions in serum Gd-IgA1, and the reduced Gd-IgA1 level was significantly correlated with improvements in proteinuria ( 67 ). Additionally, some studies have shown that the recurrence of IgAN in allograft kidneys is associated with high serum Gd-IgA1 levels ( 68 – 70 ). Moreover, serum Gd-IgA1 level may be a potential biomarker for the diagnosis and activity assessment of recurrent IgAN after kidney transplantation ( 71 – 73 ).…”

Section: Discussionmentioning

confidence: 99%

“…Atacicept, a blocker of BLyS and APRIL, has the potential to improve proteinuria and renal function and has an acceptable safety profile in patients with IgAN. Importantly, atacicept treatment led to dose-dependent reductions in serum Gd-IgA1, and the reduced Gd-IgA1 level was significantly correlated with improvements in proteinuria (67). Additionally, some studies have shown that the recurrence of IgAN in allograft kidneys is associated with high serum Gd-IgA1 levels (68-70).…”

Section: Findings In the Context Of Other Literaturementioning

confidence: 98%

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Diagnostic and prognostic value of galactose-deficient IgA1 in patients with IgA nephropathy: an updated systematic review with meta-analysis

Zeng,

Wang,

et al. 2023

Front. Immunol.

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ObjectivesGalactose-deficient IgA1 (Gd-IgA1) is a critical effector molecule in the pathogenesis of IgA nephropathy (IgAN), a leading renal disease without noninvasive assessment options. This updated systematic review aimed to determine the diagnostic and prognostic value of Gd-IgA1 assessment in biological fluids in patients with IgAN.MethodsPRISMA guidelines were followed in this review. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, VIP Information/China Science and Technology Journal Database, and WANFANG for studies published between database inception and January 31, 2023. Eligible studies that evaluated aberrant IgA1 glycosylation in IgAN patients relative to controls were identified, and random effects meta-analyses were used to compare Gd-IgA1 levels in different groups. The quality of the evidence was assessed using the Newcastle-Ottawa Scale. This study was registered on PROSPERO (CRD42022375246).FindingsOf the 2727 records identified, 50 were eligible and had available data. The mean Newcastle-Ottawa Scale score was 7.1 (range, 6–8). Data synthesis suggested that IgAN patients had higher levels of blood and/or urine Gd-IgA1 compared with healthy controls (standard mean difference [SMD]=1.43, 95% confidence interval [CI]=1.19−1.68, P<0.00001), IgA vasculitis patients (SMD=0.58, 95% CI=0.22−0.94, P=0.002), and other kidney disease patients (SMD=1.06, 95% CI=0.79−1.33, P<0.00001). Moreover, patients with IgAN had similar levels of serum Gd-IgA1 compared to first-degree relatives (SMD=0.38, 95% CI= -0.04−0.81, P=0.08) and IgA vasculitis with nephritis patients (SMD=0.12, 95% CI= -0.04−0.29, P=0.14). In addition, ten studies demonstrated significant differences in serum Gd-IgA1 levels in patients with mild and severe IgAN (SMD= -0.37, 95% CI= -0.64−-0.09, P=0.009).ConclusionsHigh serum and urine Gd-IgA1 levels suggest a diagnosis of IgAN and a poor prognosis for patients with this immunological disorder. Future studies should use more reliable and reproducible methods to determine Gd-IgA1 levels.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375246, identifier CRD42022375246.

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Section: Discussionmentioning

confidence: 99%

Section: Findings In the Context Of Other Literaturementioning

confidence: 98%

Diagnostic and prognostic value of galactose-deficient IgA1 in patients with IgA nephropathy: an updated systematic review with meta-analysis

Zeng,

Wang,

et al. 2023

Front. Immunol.

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“…Evaluation of these assessments should be made in future prospective cohorts. Finally, although an association between anti-Gd-IgA1-specific autoantibodies and IgA deposition in the allograft has been reported [ 28 ], anti-Gd-IgA1-specific autoantibodies were not investigated in this study. However, other researchers found that serum anti-Gd-IgA1-specific autoantibodies did not predict outcome in the native kidney [ 36 ].…”

Section: Discussionmentioning

confidence: 98%

“…KM55 staining has also been found to be positive in allograft kidneys with IgAN [ 24 , 25 ]. It has also been reported that serum and urinary Gd-IgA1 quantification is useful for evaluation of the activity of IgAN in the native kidney [ 18 , 26 , 27 ], and the recurrence of IgAN in allograft kidneys is associated with a high Gd-IgA1 levels [ 28 – 30 ]. However, until now, there has been no system for classification of IgA deposition in allografts that includes both serological and histopathological assessment of Gd-IgA1.…”

Section: Introductionmentioning

confidence: 99%

Serological and histopathological assessment of galactose-deficient immunoglobulin A1 deposition in kidney allografts: A multicenter prospective observational study

et al. 2023

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Background Recurrent immunoglobulin A (IgA) nephropathy is an important risk factor for kidney allograft loss. However, there is no classification system for IgA deposition in kidney allografts based on serological and histopathological evaluation of galactose-deficient IgA1 (Gd-IgA1). This study aimed to establish a classification system for IgA deposition in kidney allografts based on serological and histological evaluation of Gd-IgA1. Methods This multicenter prospective study included 106 adult kidney transplant recipients in whom an allograft biopsy was performed. Serum and urinary Gd-IgA1 levels were investigated in 46 transplant recipients who were IgA-positive and classified into four subgroups according to the presence or absence of mesangial Gd-IgA1 (KM55 antibody) deposits and C3. Results Minor histological changes without an acute lesion were observed in recipients with IgA deposition. Fourteen (30%) of the 46 IgA-positive recipients were KM55-positive and 18 (39%) were C3-positive. The C3 positivity rate was higher in the KM55-positive group. Serum and urinary Gd-IgA1 levels were significantly higher in KM55-positive/C3-positive recipients than in the other three groups with IgA deposition. Disappearance of IgA deposits was confirmed in 10 of 15 IgA-positive recipients in whom a further allograft biopsy was performed. The serum Gd-IgA1 level at the time of enrollment was significantly higher in recipients in whom IgA deposition continued than in those in whom it disappeared (p = 0.02). Conclusions The population with IgA deposition after kidney transplantation is serologically and pathologically heterogeneous. Serological and histological assessment of Gd-IgA1 is useful for identifying cases that should be carefully observed.

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“…In this report, the IgAN recurrence group demonstrated significantly higher serum αIgA levels at the time of recurrence confirmation. The IgAN recurrence group also exhibited higher intragraft αIgA and relatively higher ICs than those of a non-IgAN recurrence group [62]. According to these reports, therefore, it is reasonable to believe that GdIgA1 and αIgA are key molecules in IgAN recurrence and important targets to prevent recurrence.…”

Section: Iga Nephropathymentioning

confidence: 92%

Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants

Nakamura

Shirouzu

2021

JCM

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The advances in acute phase care have firmly established the practice of organ transplantation in the last several decades. Then, the next issues that loom large in the field of transplantation include antibody-mediated rejection (ABMR) and recurrent primary disease. Acute ABMR is a daunting hurdle in the performance of organ transplantation. The recent progress in desensitization and preoperative monitoring of donor-specific antibodies enables us to increase positive outcomes. However, chronic active ABMR is one of the most significant problems we currently face. On the other hand, recurrent primary disease is problematic for many recipients. Notably, some recipients, unfortunately, lost their vital organs due to this recurrence. Although some progress has been achieved in these two areas, many other factors remain largely obscure. In this review, these two topics will be discussed in light of recent discoveries.

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The Abundance of Antigalactose-deficient IgA1 Autoantibodies Results in Glomerular Deposition and IgA Nephropathy Recurrence After Renal Transplantation

Abstract: The clinical trial registration number is UMIN000023787.

Cited by 5 publications

References 4 publications

Diagnostic and prognostic value of galactose-deficient IgA1 in patients with IgA nephropathy: an updated systematic review with meta-analysis

Diagnostic and prognostic value of galactose-deficient IgA1 in patients with IgA nephropathy: an updated systematic review with meta-analysis

Serological and histopathological assessment of galactose-deficient immunoglobulin A1 deposition in kidney allografts: A multicenter prospective observational study

Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants

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