scholarly journals Clinical relevance of glomerular IgM deposition in patients with lupus nephritis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Fengmei Wang ◽  
Jirong Yu ◽  
Lei Zhang ◽  
Yan Zhang ◽  
Jie Zhang ◽  
...  

Abstract 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.

2021 ◽  
Author(s):  
Fengmei Wang ◽  
Jirong Yu ◽  
Lei zhang ◽  
Yan Zhang ◽  
Jie Zhang ◽  
...  

Abstract 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.


2020 ◽  
Vol 10 (1) ◽  
pp. e06-e06
Author(s):  
Marwa M Shakweer ◽  
Lobna S Shash

Introduction: Syndecan 1 (SCD1) is a lectin expressed at the surface of renal tubular epithelial cells and plasma cells. In epithelial cells, cell surface syndecan1 is cleaved by inflammation-induced proteases (eg, ADAMTS, MMP), since loss of cell surface syndecan1 is associated with higher susceptibility to cell damage. Objectives: To explore a potential additional value of SCD1 immunohistochemical expression in lupus nephritis specimens of different ISN/RPS classes and NIH activity and chronicity indices. Patients and Methods: This retrospective study included 50 renal biopsy specimens diagnosed as lupus nephritis at the pathology laboratory, and electron microscopy (EM) laboratory of Ain-Shams University specialized hospitals. Data were collected from records as personal data, medical history and laboratory results including serum creatinine and proteinuria. Immunohistochemical expression of syndecan-1 was evaluated in renal tubular epithelial cells (TECs) followed by correlation with different clinicopathological parameters. Results: Fifty renal biopsy specimens with lupus nephritis including 14 cases of class II, 4 cases of class III, 20 cases of class IV and 12 cases of class V were re-evaluated. The mean serum creatinine was 1.57 ± 0.67 mg/dL. Nine cases (18%) were negative for proteinuria, while 41 cases (82%) were presented with proteinuria with a mean of 1.5 ± 0.9 g/24 h. There was no statistically significant difference in the percentage of SCD-1 expression with different lupus classes. Serum creatinine and albumin showed a statistically significantly different correlation with semiquantitative score of SCD-1 expression. The highest value of creatinine detected with score 1 of SCD-1 expression (P=0.038) and the highest value of urinary albumin was recorded with score 1 of SCD-1 expression. Accordingly, the lowest mean of urinary albumin recorded in SCD-1 score 3 (P<0.001). There was a weekly negative association between loss of SCD-1 expression and increased NIH activity and chronicity indices. Conclusion: Loss of syndecan immunohistochemical expression in renal TECs in lupus nephritis is highly associated with proteinuria and elevated serum creatinine and can be used as a predictive marker for disease severity and progression.


2021 ◽  
Vol 11 (8) ◽  
pp. 693
Author(s):  
Corina Daniela Ene ◽  
Simona Roxana Georgescu ◽  
Mircea Tampa ◽  
Clara Matei ◽  
Cristina Iulia Mitran ◽  
...  

The interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydrocarbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Our study included 38 SLE patients with lupus nephritis (LN group), 44 SLE patients without renal impairment (non-LN group) and 40 healthy volunteers as control group. In the present paper, we evaluated serum lipid peroxidation, DNA oxidation, oxidized proteins, carbohydrate oxidation, and endogenous protective systems. We detected defective DNA repair mechanisms via 8-oxoguanine-DNA-glycosylase (OGG1), the reduced regulatory effect of soluble receptor for advanced glycation end products (sRAGE) in the activation of AGE-RAGE axis, low levels of thiols, disulphide bonds formation and high nitrotyrosination in lupus nephritis. All these data help us to identify more molecular mechanisms to counteract oxidative stress in LN that could permit a more precise assessment of disease prognosis, as well as developing new therapeutic targets.


Lupus ◽  
2020 ◽  
pp. 096120332097904
Author(s):  
Eman Ahmed Hafez ◽  
Sameh Abd El-mottleb Hassan ◽  
Mohammed Abdel Monem Teama ◽  
Fatma Mohammed Badr

Objective Lupus nephritis (LN) is closely associated with hyperuricemia, and uric acid is considered a risk factor for renal involvement in systemic lupus erythematosus (SLE). This study aimed to examine the association between serum uric acid (SUA) level and LN development and progression in SLE patients with normal renal function. Methods A total of 60 SLE patients with normal renal function from Ain Shams University Hospital were selected and assigned to group 1 (30 patients with LN) and group 2 (30 patients without LN). All patients were subjected to history taking, clinical examination, disease activity assessment based on SLE disease activity index (SLEDAI) and renal SLEDAI (SLEDAI-R) scores, and laboratory investigations, including as SUA, complete blood count, blood urea nitrogen (BUN), serum creatinine, creatinine clearance, urine analysis, protein/creatinine ratio, 24-h urinary protein excretion, Antinuclear antibodies (ANA), anti-dsDNA antibody, and serum complement (C3, C4). Results Disease duration, SLEDAI score, and SUA level were higher in group 1 than in group 2 (p < 0.001). SUA level was positively correlated with SLEDAI and SLEDAI-R scores, proteinuria, urinary casts, renal biopsy class, disease activity and chronicity indices, BUN level, and serum creatinine level but was negatively correlated with creatinine clearance (p < 0.05). SUA was a predictor of LN development in SLE patients (sensitivity, 83.3%; specificity, 70%). Conclusion SUA is associated with the development of lupus nephritis in patients with normal kidney function also SUA in-dependently correlated with disease activity and chronicity in LN.


2012 ◽  
Vol 8 (5) ◽  
pp. 849-852 ◽  
Author(s):  
Mare Lõhmus ◽  
Sharon Moalem ◽  
Mats Björklund

One common physiological phenomenon that is involved both in infectious and in malignant processes is the reduction in appetite: disease anorexia. An increase in plasma levels of leptin with inflammation is thought to be involved in this process. However, from an evolutionary perspective, in certain cases, it would be more adaptive for an internal parasite to stimulate the appetite of the host instead of causing its suppression. We tested whether a parasitic infection with the larvae of the helminth parasite Taenia taeniaformis affects the levels of appetite-regulating proteins, such as leptin, ghrelin and neuropeptide-Y (NPY) in wild yellow-necked mouse ( Apodemus flavicollis ). We found that infected mice had lower plasma levels of leptin and increased levels of NPY than the uninfected subjects. Ghrelin levels were not associated with the occurrence of the parasites; however, these levels strongly correlated with the levels of NPY. This study suggests a possible manipulation by parasitic larvae of appetite regulation in infected subjects.


2000 ◽  
Vol 130 (2) ◽  
pp. 243-248 ◽  
Author(s):  
Marie-Anne Levrat-Verny ◽  
Stephen Behr ◽  
Vikkie Mustad ◽  
Christian Rémésy ◽  
Christian Demigné

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Jianhua Dong ◽  
Li Huang ◽  
Chuan Li ◽  
Ling Kong ◽  
Lixuan Huang ◽  
...  

Abstract Background and Aims The Study delves into the clinical efficacy and advantages of centrifugal double filtration plasmapheresis on severe lupus nephritis (LN) by comparing it with membranous double filtration plasmapheresis (DFPP). Method A retrospective analysis was performed on 56 patients who were diagnosed with severe LN and had received DFPP treatment from May 2016 and January 2020. Of them, 38 were given centrifugal DFPP and had their plasma centrifuged in a blood cell separator, and 18 were given membranous DFPP and had their plasma centrifuged in an MPS07 plasma separator. An EC20W plasma component separator was used as the secondary filter to reprocess the separated plasma of all of them. The two DFPPs were compared for differences in clinical efficacy, vascular access, dosage of anticoagulant, treatment cost and adverse events in patients with severe LN. Results Of the 56 severe LN patients (including 43 females and 13 males), the median of age of onset was 29 years old, the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) was 18.6±6.0 points and the serum creatinine was 402(294,553) umol/L, and all patients had acute kidney injury and 51 of them (91.1%) required renal replacement therapy (RRT). A total of 142 DFPPs were performed, including 97 centrifugal DFPPs and 45 membranous DFPPs. After treatment and at Month 3 of follow-up visit, patients in both the centrifugal DFPP group and the membranous DFPP group had ANA, AdsDNA titer, quantitative urinary protein, urinary red blood cell count and serum creatinine significantly dropped and hemoglobin significantly increased over those before treatment, the differences in which between the two groups, however, were not statistically significant. The centrifugal DFPP group had a more significant drop in complements C3 and C4 after treatment. Comparison of the data before and after a single DFPP treatment showed that the membranous DFPP group had a more significantly longer prothrombin time, but there were no differences in partial prothrombin time, fibrinogen and platelet change between the two groups. At Month 3 of follow-up visit, 31 of the 51 RRT patients (60.8%) (including 34 given centrifugal DFPP and 17 given membranous DFPP) were released from dialysis, including 23 given centrifugal DFPP and 8 given membranous DFPP. In the membranous DFPP group, all patients had the vascular access built via the central venous catheter, while in the centrifugal DFPP group, 6 patients (15.8%) had the vascular access built by puncturing into the artery or vein. The dosage of the anticoagulant, the low molecular weight heparin, to the centrifugal DFPP group was significantly lower than that to the membranous DFPP group (1174±243 vs 4106±399IU, P&lt;0.001), and in the centrifugal DFPP group, 29 patients (76.3%) were given 4% citric acid alone for anti-coagulation. No blood coagulation occurred. In terms of treatment consumables, the membranous DFPP group had a significantly higher cost than the centrifugal DFPP group (RMB4340.2±237.0 vs 5677.0±0.0, P&lt;0.001). Two patients (4.4%) in the membranous DFPP group developed skin ectasis, epistaxis or aggravated alveolar hemorrhage after treatment, and four patients (4.1%) in the centrifugal DFPP group developed perioral numbness, numbness in distal extremities or tetany during treatment, which was alleviated after calcium supplementation. Conclusion Centrifugal DFPP differed little from membranous DFPP in clinical efficacy in severe LN patients, but had lower anti-coagulation requirements, cost less on treatment consumables, and caused no severe adverse events, so it can be used as an important means to treat severe LN.


2019 ◽  
Vol 38 (6) ◽  
pp. 2668-2676 ◽  
Author(s):  
A.C.B. van Orten-Luiten ◽  
A. Janse ◽  
E. Verspoor ◽  
E.M. Brouwer-Brolsma ◽  
R.F. Witkamp

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