Co-Deposition of IgM and C3 May Indicate Unfavorable Renal Outcomes in Adult Patients with Primary Focal Segmental Glomerulosclerosis

Mirioglu, Safak; Çalışkan, Yaşar; Dirim, Ahmet Burak; Istemihan, Zulal; Akyildiz, Arif; Yazıcı, Halil; Türkmen, Aydın; Kiliçaslan, İşın; Sever, Mehmet Şükrü

doi:10.1159/000501827

Cited by 15 publications

(19 citation statements)

References 24 publications

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“…C3 staining was associated with worse renal outcomes in one study but not another (23,25). The combination of IgM and C3 staining was associated with both renal dysfunction and poor renal survival previously (23,24). In our cohort, C3, IgM, or a combination of IgM/C3 staining on immunofluorescence were not associated with reduced renal survival (Supplemental Figure 3).…”

Section: Resultsmentioning

confidence: 51%

“…Strassheim et al reported compelling evidence from a murine model that IgM binds in the glomerulus and activates complement to cause increased proteinuria (21). Two FSGS cohort studies found no association between IgM staining on immunofluorescence and long term renal survival in FSGS (23,24). C3 staining was associated with worse renal outcomes in one study but not another (23,25).…”

Section: Resultsmentioning

confidence: 99%

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Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression

et al. 2021

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Background: Focal segmental glomerulosclerosis (FSGS) is a heterogeneic glomerular disease. Risk factors for end- stage kidney disease (ESKD) and impact of immunosuppression treatment (IST) has varied in previously published cohorts. These cohorts were limited by relatively small case numbers, short follow up, lack of racial/ethnic diversity, a mix of adult and pediatric patients, lack of RAAS inhibition, or lack of subgroup analysis of IST. Methods: We compared demographics, clinical characteristics, histopathology and IST to long term renal survival in a large, ethnically diverse, adult cohort of 338 biopsy-proven FSGS cases with long term follow up in the era of RAAS inhibition using data from the United States Department of Defense health care network. Results: Multivariate analysis showed that nephrotic range proteinuria (NRP), estimated glomerular filtration rate <60 ml/min/1.73m2, hypoalbuminemia, interstitial fibrosis and tubular atrophy, and interstitial inflammation at diagnosis as well as the absence of remission were all associated with worse long term renal survival. IgM, C3, and a combination of IgM/C3 immunofluorescence staining were not associated with reduced renal survival. IST was not associated with improved renal survival in the whole cohort, or in a subgroup with NRP. However, IST was associated with better renal survival in a subgroup of FSGS cases with both NRP and hypoalbuminemia and hypoalbuminemia alone. Conclusion: Our study suggests that IST should be reserved for FSGS patients with nephrotic syndrome. It also introduces interstitial inflammation as a potential risk factor for ESKD and does not support the proposed pathogenicity of IgM and complement activation.

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Section: Resultsmentioning

confidence: 51%

Section: Resultsmentioning

confidence: 99%

Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression

et al. 2021

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“…On the basis of the above relevance of glomerular IgM deposition in patients with LN, it is important to evaluate the predictive value of glomerular IgM deposition for long-term renal outcome in LN. Recently, several studies showed that IgM deposition predicted renal outcome in patients with IgAN, FSGS and diabetic nephropathy [ 7 , 9 , 27 , 28 ]. However, owing to the relatively good treatment response of LN and our relatively small follow-up population, we failed to draw any convincing conclusions regarding the predictive value of glomerular IgM deposition in our study.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of glomerular IgM deposition in patients with lupus nephritis

Wang

Zhang

et al. 2021

BMC Immunol

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Background The aim of the study was to investigate the clinical relevance of IgM deposition in patients with lupus nephritis (LN) in a large cohort. Results 217 patients with renal biopsy-proven active LN were enrolled. The associations between glomerular IgM deposition and clinicopathological parameters were further analyzed. IgM deposition was positively correlated with glomerular C1q and C3 deposition moderately (r = 0.436, P < 0.001; r = 0.408, P < 0.001, respectively), and inversely correlated with plasma levels of C3 and CFH mildly (r = − 0.138, P = 0.043; r = − 0.147, P = 0.037, respectively). By multivariate analysis, we found that glomerular IgM deposition independently contributed to glomerular C3 deposition in patients with LN (OR = 2.002, 95% CI 1.295–3.094, P = 0.002). In addition, we also found that patients with IgM 0–2+ had similar plasma CFH levels, but in patients with IgM3+–4+, plasma CFH levels were significantly lower (300.4 ± 155.8 μg/mL vs. 429.9 ± 187.5 μg/mL, P < 0.001). Furthermore, patients with high density of glomerular IgM and low levels of CFH had heavier proteinuria, higher serum creatinine and lower plasma C3 levels (5.7 ± 3.1 g/d vs. 4.7 ± 3.5 g/d, P = 0.037; 150.1 ± 121.0 μmol/L vs. 105.6 ± 97.1 μmol/L, P = 0.005; 0.3 ± 0.2 μg/L vs. 0.4 ± 0.2 μg/L, P = 0.04, respectively), comparing with those with low density of glomerular IgM and low levels of CFH. Conclusions Our results suggested the involvement of glomerular deposited IgM in complement activation and renal injury in LN.

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“…On the basis of the above relevance of glomerular IgM deposition in patients with lupus nephritis, it is important to evaluate the predictive value of glomerular IgM deposition for long-term renal outcome in lupus nephritis. Recently, several studies showed that IgM deposition predicted renal outcome in patients with IgAN, FSGS and diabetic nephropathy [7,9,22,23].…”

Section: Discussionmentioning

confidence: 99%

“…In lupus nephritis, it is mostly suggested to be initiated by the glomerular deposition of nephritogenic IgG type autoantibodies, which caused the complement activation [3,[19][20][21]. IgM and complement-mediated injury may be secondary phenomena after the IgG type autoantibodies insult [10,[22][23][24][25]. Consequently, we further compared the plasma CFH levels among different intensity of glomerular IgG deposition.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of glomerular IgM deposition in patients with lupus nephritis

Wang¹,

JiRong²,

Zhang³

et al. 2021

Preprint

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Background The aim of the study was to investigate the clinical relevance of IgM deposition in patients with LN in a large cohort. Results 217 patients with renal biopsy–proven lupus nephritis were enrolled. The associations between glomerular IgM deposition and clinicopathological parameters were further analyzed. IgM deposition was positively correlated with glomerular C1q and C3 deposition moderately (r = 0.436, P < 0.001; r = 0.408, P < 0.001, respectively), and inversely correlated with plasma levels of C3 and CFH mildly (r=-0.138, P = 0.043; r=-0.147, P = 0.037, respectively). By multivariate analysis, we found that glomerular IgM deposition independently contributes to glomerular C3 deposition in patients with lupus nephritis (OR = 2.002, 95% CI: 1.295–3.094, P = 0.002). In addition, we also found that patients with IgM 0+-2 + had similar plasma CFH levels, but in patients with IgM3+-4+, plasma CFH levels were significantly lower (300.4 ± 155.8µg/ml vs. 429.9 ± 187.5µg/ml, P < 0.001). Furthermore, patients with high density of glomerular IgM and low levels of CFH had heavier proteinuria, higher serum creatinine and lower plasma C3 levels (5.7 ± 3.1g/d vs. 4.7 ± 3.5g/d, P = 0.037;150.1 ± 121.0µmol/L vs. 105.6 ± 97.1µmol/L, P = 0.005; 0.3 ± 0.2µg/L vs. 0.4 ± 0.2µg/L, P = 0.04, respectively), comparing with those with low density of glomerular IgM and low levels of CFH. Conclusions Our results suggested IgM might bind to injury-associated epitopes and be involved in disease progression and provided a possible relevance of CFH and IgM in the process of alternative pathway (AP) activation.

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Co-Deposition of IgM and C3 May Indicate Unfavorable Renal Outcomes in Adult Patients with Primary Focal Segmental Glomerulosclerosis

Cited by 15 publications

References 24 publications

Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression

Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression

Clinical relevance of glomerular IgM deposition in patients with lupus nephritis

Clinical relevance of glomerular IgM deposition in patients with lupus nephritis

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