Identification of IgA autoantibodies targeting mesangial cells redefines the pathogenesis of IgA nephropathy

Nihei, Yasunori; Haniuda, Kei; Higashiyama, Mizuki; Asami, Shohei; Iwasaki, H.; Fukao, Yusuke; Nakayama, Maiko; Suzuki, Hitoshi; Kikkawa, Mika; Kazuno, Saiko; Miura, Yoshiki; Suzuki, Yusuke; Kitamura, Daisuke

doi:10.1126/sciadv.add6734

Cited by 28 publications

(22 citation statements)

References 56 publications

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“…Recently, Nihei et al. ( 20 ) demonstrated the presence of IgA autoantibodies directed against a protein expressed on the membrane surface of mesangial cells in 30% of patients with IgAN. This mechanism, which remains to be confirmed, may be part of the breakdown in peripheral tolerance induced by ICIs.…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor therapy associated with IgA nephropathy: a case report and literature review

Chabannes,

Lisri,

Lang

et al. 2024

Front. Immunol.

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Immune checkpoint inhibitors (ICIs) dramatically improve the prognosis of many malignancies but at the cost of numerous side effects, which may limit their benefits. Acute kidney injury associated with immune checkpoint inhibitors most frequently are acute tubulointerstitial nephritis (ATIN), but various cases of glomerulonephritis have also been reported. Herein, we report a case of severe IgA nephropathy (IgAN) associated with ICIs and carry out a literature review. IgAN was diagnosed in a median time of 5 months (range 1–12 months) after the initiation of ICIs, with heterogeneous severity, and usually treated by corticosteroid and discontinuation of ICIs. In contrast to our case, renal outcomes in literature were often favorable, with recovery of renal function and a reduction in proteinuria on treatment. Although IgAN related to ICIs is a much rarer complication than ATIN, it may still be underdiagnosed. Careful questioning and screening for asymptomatic hematuria should be performed before using ICIs.

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Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor therapy associated with IgA nephropathy: a case report and literature review

Chabannes,

Lisri,

Lang

et al. 2024

Front. Immunol.

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“…Recently, novel biomarkers, including serum Gd-IgA1, serum glycan-specific antibodies and urinary Gd-IgA1, have been reported as potentially helpful in diagnosing IgAN [ 61–63 ]. Moreover, our research group recently reported anti–βII-spectrin IgA might also be involved in the pathogenesis of IgAN and could be the candidate for its disease-specific biomarker [ 64 ]. The screening system using novel biomarkers in addition to conventional screening can potentially reduce medical expenses [ 65 ].…”

Section: Timing Of Diagnosismentioning

confidence: 99%

Ethnicity and IgA nephropathy: worldwide differences in epidemiology, timing of diagnosis, clinical manifestations, management and prognosis

Lee,

Suzuki,

Nihei

et al. 2023

Clinical Kidney Journal

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Immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis, is one of the major causes of end-stage renal disease. Significant variances in epidemiology, clinical manifestation, timing of diagnosis, management and renal prognosis of IgAN have been reported worldwide. The incidence of IgAN is the most frequent in Asia, followed by Europe, and lower in Africa. Moreover, Asian patients show more frequent acute lesions in renal histology and present poorer renal outcomes compared with Caucasians. The comorbidities also show the difference between Asians and Caucasians. Although the frequency of gross hematuria with upper respiratory tract infection is not different, comorbidities with gastrointestinal diseases are reported to be higher in Europe. Recently, genetic studies for variant ethnic patients revealed widely ranging genetic risks in each ethnicity. A genetic risk score is most elevated in Asians, intermediate in Europeans and lowest in Africans, consistent with the disease prevalence of IgAN globally. Ethnic variance might be highly affected by the difference in genetic background. However, it is also essential to mention that the different timing of diagnosis due to variant urinary screening systems and the indication for renal biopsy in different countries may also contribute to these variances. The management of IgAN also varies internationally. Currently, several novel therapies based on the pathogenesis of IgAN are being assessed and are expected to become available soon. Further understanding the ethnic variance of IgAN might help establish individualized care for this disease. Here, we review the issues of ethnic heterogeneities of IgAN.

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“…The pathogenesis of IgAN is made even more complex by recent observations that IgA-secretory plasmablasts can migrate from the mucosae to the kidney [ 18 ] and produce serum IgA against mesangial antigens, such as βII-spectrin [ 18 , 20 ].…”

Section: Systemic Glucocorticoidsmentioning

confidence: 99%

Systemic and targeted steroids for the treatment of IgA nephropathy

Locatelli,

Del Vecchio,

Ponticelli

2023

Clinical Kidney Journal

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Immunoglobulin A nephropathy (IgAN) is a common glomerulonephritis partially correlated with mucosal immune system dysfunction. Progressive renal failure occurs in many patients, with about 30–50% of the patients with IgAN developing end-stage kidney disease (ESKD). Many treatments have been used for decades, despite uncertainty about their effectiveness and the ideal dose. Randomised controlled trials reported that systemic glucocorticoids can be an effective treatment for patients with persistent and significant proteinuria despite renin-angiotensin system inhibitors use possibly causing systemic side effects. The primary focus of IgAN management should be based on optimised supportive care, including renin-angiotensin system (RAS) blockade and now SGLT2 inhibitors. The novel targeted-release formulation (TRF) of budesonide has been tested to reduce the adverse events of systemic steroids by delivering the drug to the distal ileum. The local efficacy of TRF-budesonide may represent a novel and promising approach to treating IgAN. Two clinical trials showed that TRF-budesonide could significantly reduce proteinuria and haematuria and possibly preserve renal function while significantly reducing the side effects. However, the limited number of treated patients and the relatively short follow-up suggest caution before considering budesonide superior to the current six-months steroid pulses scheme. Long-term data on the efficacy and safety of TRF budesonide are awaited, together with the design of trials with a head-to-head comparison with systemic steroids before considering TRF-budesonide as the standard of care treatment for IgAN nephropathy.

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Identification of IgA autoantibodies targeting mesangial cells redefines the pathogenesis of IgA nephropathy

Cited by 28 publications

References 56 publications

Immune checkpoint inhibitor therapy associated with IgA nephropathy: a case report and literature review

Immune checkpoint inhibitor therapy associated with IgA nephropathy: a case report and literature review

Ethnicity and IgA nephropathy: worldwide differences in epidemiology, timing of diagnosis, clinical manifestations, management and prognosis

Systemic and targeted steroids for the treatment of IgA nephropathy

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