Serum C3 Levels Research Articles

Association of Complement C3 With Incident Type 2 Diabetes and the Mediating Role of BMI: A 10-Year Follow-Up Study.

Impairment of immune and inflammatory homeostasis is reported to be one of the causal factors of diabetes. However, the association of complement C3 levels with incident diabetes in humans remains unclear. This study aimed to examine the association between C3 levels and incident type 2 diabetes mellitus (T2DM), and further explore the potential mediating role of body mass index (BMI) in C3-T2DM associations. We determined serum C3 levels of 2662 nondiabetic middle-aged and elderly (64.62 ± 7.25 years) individuals from the Dongfeng-Tongji cohort at baseline. Cox regression was employed to examine the incidence of T2DM in relationship to C3 levels during 10 years of follow-up. Mediation analysis was further applied to assess potential effect of BMI on the C3-T2DM associations. Overall, 711 (26.7%) participants developed T2DM during 23 067 person-years of follow-up. Higher serum C3 was significantly associated with higher risk of incident T2DM after full adjustment (HR [95% CI] = 1.16 [1.05, 1.27]; per SD higher). Compared with the first quartile of C3 levels, the HR in the fourth quartile was 1.52 (95% CI = [1.14, 2.02]; Ptrend = 0.029). Robust significant linear dose-response relationship was observed between C3 levels and BMI (Poverall < 0.001, Pnonlinear = 0.96). Mediation analyses indicated that BMI might mediate 41.0% of the associations between C3 and T2DM. The present prospective study revealed that C3 could be an early biomarker for incident T2DM, and that BMI might play a potential mediating role in the C3-T2DM associations, which provided clues for the pathogenesis of diabetes.

Effects of the Replacement of Dietary Fish Meal with Defatted Yellow Mealworm (Tenebrio molitor) on Juvenile Large Yellow Croakers (Larimichthys crocea) Growth and Gut Health.

Simple SummaryFish meal is the most common protein source in aquatic feeds. The decline of fishery resources and the increased demand have led to a shortage of fish meal resources in recent years. To ensure the sustainable development of the aquaculture industry, it is crucial to find a low-price, high-quality protein source to replace fish meal. In this study, substituting fish meal of large yellow croakers (Larimichthys crocea) diets with defatted yellow mealworm (Tenebrio molitor) test was carried out. The results showed that the dietary fish meal could be replaced by 15% defatted yellow mealworm in feeds containing 40% fish meal without adversely affecting the growth of large yellow croakers, and to some extent improving the immunity of the organism. Substitution levels of 15% or more are beneficial for digestive enzymes. In addition, the moderate addition of defatted yellow mealworm improves intestinal health by improving the structure and microbial composition of the gut.This study was conducted to investigate the effects of Tenebrio molitor meal (TM) replacement for fish meal (FM) on growth performance, humoral immunity, and intestinal health of juvenile large yellow croakers (Larimichthys crocea). Four experimental diets were formulated by replacing FM with TM at different levels—0% (TM0), 15% (TM15), 30% (TM30), and 45% (TM45). Triplicate groups of juveniles (initial weight = 11.80 ± 0.02 g) were fed the test diets to apparent satiation two times daily for eight weeks. There was no significant difference in final body weight (FBW) and weight gain rate (WG) among TM0, TM15, and TM30, while TM45 feeding significantly reduced the FBW and WG. Compared with TM0, AKP activity in serum was significantly decreased in TM45, while the TM15 group remarkably increased LZM activity. TM30 showed significantly higher serum C3 levels compared to the TM0 group, while the TM addition groups decreased the C4 levels significantly in the serum. In terms of intestinal histology, the addition of TM increased the height and thickness of the intestinal villus and also increased the thickness of the intestinal muscles significantly. The addition of TM significantly reduced the serum DAO and D-lactate concentrations. The results of 16S rRNA gene sequencing showed that the addition of TM significantly enhanced the relative abundance of Bacilli and Lactobacillus and contributed to the decrease in the relative abundance of Plesiomonas. In addition, the TM30 and TM45 groups significantly reduced the abundance of Peptostreptococcaceae. Overall, our results indicated that TM could be a viable alternative protein source, 6.7% TM supplantation (replacing 15% FM) in large yellow croaker feed improved humoral immunity and intestinal health with no adverse effects on growth. Furthermore, the replacement of FM with 30% and 45% TM adversely affects growth and humoral immunity.

Serum interleukin-33 (IL-33) in children with active systemic lupus erythematosus: A cross-sectional study

Interleukin-33 (IL-33) is a member of the IL-1 cytokine family and is associated with the development of different autoimmune diseases as systemic lupus erythematosus (SLE). So, the purpose of this cross-sectional study was to measure the serum IL-33 in children with SLE (c-SLE) in relation to their SLE disease activity index. This study was conducted upon 50 c-SLE patients in comparison to 50 normal matched children as a control group. Disease activity was assessed according to SLE Disease Activity Index (SLEDAI-2K). Serum IL-33 was measured by an Enzyme-linked immunosorbent assay (ELISA). Serum IL-33 was significantly higher in c-SLE patients (median: 157.47, IQR:64.49-237.57ng/l) than controls (median: 10.9, IQR: 10.04-12.51ng/L) (P= 0.001) and negatively correlated with serum C3 and C4 levels. Serum IL-33 levels were significantly higher in high disease activity status (HDAS) patients (SLEDAI-2K ≥ 10) (298.47 ± 78.84ng/l) than lupus low disease activity status (LLDAS) patients (SLEDAI-2K < 10) (112.18 ± 16.23ng/l) (P= 0.001). The receiver operating characteristic (ROC) curve analysis revealed that the best cutoff of serum IL-33 level to predict the disease activity was ≥141.3 ng/l with a sensitivity of 93%, a specificity of 90% and accuracy 97%. We concluded that serum IL-33 was higher in c-SLE patients and positively related to the disease activity index so could be used as a disease activity marker.

Immunological profile of erythema nodosum and their relationship of C-reactive protein level and erythrocyte sedimentation rate: A retrospective analysis of 61 patients.

This experiment was carried out to investigate changes in lymphocyte subpopulation, immunoglobulins (Igs), and complements, and also to explore the relationship between these immune indices and C-reactive protein and erythrocyte sedimentation rate in 61 patients with erythema nodosum. For this aim, a 4-year, retrospective study contained 61 patients with erythema nodosum, and 61 healthy control subjects were included from the out-patient clinic. The subpopulation of the T, B and natural killer lymphocytes and levels of IgA, IgG, IgM, complement C3, complement C4, C-reactive protein, and erythrocyte sedimentation rate from peripheral blood of them were detected. A correlation analysis was done between lymphocyte subpopulation, levels of IgA, IgG, and IgM, complement C3, complement C4 and C-reactive protein level and erythrocyte sedimentation rate in the patient group. Results showed that the percentage of CD4+ cells, CD4+/CD8+ ratio, the level of C-reactive protein and the erythrocyte sedimentation rate in the patients were higher than in controls (P<0.05). While the percentage of CD8+ cells and the serum levels of complement C3 were lower than in controls (P<0.05). There were no differences in the percentages of CD3+, B and natural killer cells and the serum levels of IgA, IgG and IgM, and complement C4 between the patients and the controls (P>0.05). IgM level was positively correlated with C-reactive protein (P<0.05) but did not correlate with an erythrocyte sedimentation rate (P>0.05). There was no correlation between lymphocyte subpopulation, levels of IgA, IgG, complement C3, complement C4 and C-reactive protein level and erythrocyte sedimentation rate (P>0.05). In conclusion, there was dysregulation of both cellular immunity and humoral immunity in patients with erythema nodosum. IgM level has a positive correlation with C-reactive protein.

WE-171. Association of serum C3 level with the presenting severity of the myasthenia gravis

WE-171. Association of serum C3 level with the presenting severity of the myasthenia gravis

Burning urticarial plaques in a middle-aged woman

Burning urticarial plaques in a middle-aged woman

Comparative analysis of complement C3 and C4 serum levels for outcome prediction in ANCA-associated renal vasculitis

BackgroundThe activation of the complement system contributes essentially to the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis. We here aimed to directly compare levels of C3 and C4 for outcome prediction in ANCA-associated renal vasculitis.MethodsSerum levels of complement components C3 and C4 were directly compared in association with clinical and outcome data in a retrospective cohort of ANCA-associated renal vasculitis.ResultsAs compared to poor outcome prediction by low levels of complement C3 (p = 0.0093), low levels of complement C4 did not associate with early requirement of kidney replacement therapy (KRT) or death (p = 0.2396). In the subgroup that experienced KRT or death, low C3 levels identified 11/14 (78.6%, p = 0.0071) and C4 levels 9/14 (64.3%, p = 0.1786) cases. Interestingly, 2/14 (14.3%) patients that experienced KRT or death had isolated C4 lowering, and combining low C3 and/or C4 levels identified 13/14 (92.3%, p < 0.0001) cases in this subgroup. Non-superiority to predict poor outcome by low C3 and/or C4 as compared to C3 alone in the total cohort was attributed to 4/24 (16.7%) patients with isolated C4 lowering in the subgroup that did not experience KRT or death.ConclusionWhile low levels of complement C3 were superior in predicting poor outcome in ANCA-associated renal vasculitis, a minor fraction with poor outcome had isolated C4 lowering not captured by serum C3 measurements. Therefore, detailed knowledge of distinct complement components contributing to kidney injury could be of relevance to improve current strategies targeting the complement system in ANCA-associated renal vasculitis.Graphical abstract

Complement C3 as a potential NAFLD predictor in an Egyptian cohort with diabetes and/or obesity

Complement system is becoming increasingly recognized as being intimately tied to obesity and other various metabolic abnormalities linked to it and may be involved in NAFLD. The goal of this study was to see if complement C3 might be used as a diagnostic and prognostic marker in NAFLD patients. Forty-one NAFLD patients and fourteen age- and gender-matched control individuals were enrolled in this study. All subjects were subjected to abdominal ultrasound examination and clinical assessment with special emphasis on the liver function enzymes, blood glucose levels, lipid profile, and kidney function tests. Non-invasive assessment of hepatic steatosis and fibrosis has evolved using serology-based scoring systems such as the Fibrosis-4 score and NAFLD Fibrosis Score (NFS). Additionally, serum levels of complement C3 were determined by the ELISA method. In this study, BMI, cholesterol, triglyceride levels, and NFS were all substantially higher in NAFLD patients compared to healthy controls. Moreover, complement C3 was considerably higher in NAFLD cases (1.52±0.29 g/L) vs. healthy controls (0.93±0.289 g/L) (p<0.001). Compared to lean people (0.93±0.29 g/L), the mean complement C3 levels were significantly higher in obese diabetes (1.69±0.29 g/L), obese non-diabetic (1.48±0.174 g/L), and diabetic non-obese patients (1.36±0.28 g/L). Using a cutoff for complement C3 1.135 (g/L) for distinguishing NAFLD patients from healthy controls has a sensitivity of 90.2% and specificity of 78.6%. In conclusion, serum complement C3 may be useful in the identification of fibrosis in non-alcoholic fatty liver disease. Moreover, complement C3 may be a promising tool for predicting the worsening of liver inflammation.

Fat Malabsorption and Ursodeoxycholic Acid Treatment in Children With Reduced Organic Solute Transporter-α (SLC51A) Expression.

Objectives:A bile acid homeostasis disorder was suspected in 2 siblings and their second cousin who presented in infancy with fat malabsorption, severe fat-soluble vitamin deficiency, rickets, and mild liver involvement. Our aims were to identify the genetic cause, describe the disease, and evaluate the response to ursodeoxycholic acid (UDCA) treatment.Methods:Whole exome sequencing, immunohistochemistry of duodenal biopsies and candidate variant testing in a cell-based model was performed. Fecal fat excretion, serum bile acids, 7α-hydroxy-4-cholesten-3-one (C4), and fibroblast growth factor 19 (FGF19) were quantified in both siblings on and off UDCA treatment.Results:A novel homozygous variant of SLC51A, which encodes the bile acid carrier organic solute transporter (OST)-α, was identified in all affected children. OSTα protein expression was readily detected by immunohistochemistry in duodenum of pediatric control subjects but not in the affected siblings. The siblings had low serum levels of bile acids and C4 and high serum levels of FGF19 consistent with repression of hepatic bile acid synthesis. On treatment with UDCA, fecal fat excretion was reduced and serum levels of C4, FGF19, and liver enzymes normalized.Conclusions:We report an apparent deficiency of OSTα associated with early onset fat malabsorption and mild liver involvement. The clinical presentation partially overlaps previous reports for 3 patients with OSTα or OSTβ deficiency and extends the clinical spectrum associated with loss of SLC51A expression. Our data suggest that repression of hepatic bile acid synthesis contributes to fat malabsorption in OSTα-OSTβ deficiency but can be partly reversed with UDCA treatment.

Abnormal lower expression of GPR183 in peripheral blood T and B cell subsets of systemic lupus erythematosus patients

G protein-coupled receptor 183 (GPR183) has been indicated to mediate the migration and localisation of immune cells in T cell-dependent antibody responses. Systemic lupus erythematosus (SLE) is a canonical autoimmune disease involving B cell-mediated tolerance destruction and excessive pathogenic autoantibody production, in which multiple GPCRs play a role. To date, there has been no systematic study regarding the expression of GPR183 in lymphocyte subsets of SLE patients. In this research, firstly, we observed the expression trends of GRP183 in various T and B cell subsets in human tonsil tissues. These lymphocyte subsets include CD4+, CD8+, naïve T, effector T, Tfh, activated Tfh, Th1, Th2, Th17, Treg, CD19+CD27-, CD19+CD27+, naïve B, germinal centre B, memory B, and plasma cells. Further, compared with healthy controls (HCs), GPR183 expression levels in above peripheral blood lymphocyte subsets of patients with SLE were reduced overall. The differential expression of GPR183 expression between inactive and active SLE patients indicates that GPR183 expression may be concerned with the disease activity of SLE. This was further confirmed through the strong negative correlation with SLEDAI score and positive correlation with serum complement protein C3, C4 and C1q levels. Further receiver operating characteristic (ROC) curve analysis revealed that GPR183 expression in circulating CD27-IgD+ B cells may be beneficial in distinguishing between inactive and active SLE patients. In addition, type I interferon stimulation could down-regulate the expression of GPR183 in peripheral blood T and B cell subsets. Aberrant expression of GPR183 may provide some novel insights into disease activity prediction and underlying pathogenesis of SLE.

Clinical and pathologic features of primary membranous nephropathy in Turkey: a multicenter study by the Turkish Society of Nephrology Glomerular Diseases Working Group

Background We aimed to evaluate the features of primary membranous nephropathy (MNP) in Turkish people. Methods This is a retrospective analysis of patients with biopsy-proven primary MNP. We obtained the data collected between 2009 and 2019 in the primary glomerulonephritis registry of the Turkish Society of Nephrology Glomerular Diseases Study Group (TSN-GOLD). Patients with a secondary cause for MNP were excluded. Clinical, demographic, laboratory, and histopathological findings were analyzed. Results A total of 995 patients with primary MNP were included in the analyses. Males constituted the majority (58.8%). The mean age was 48.4 ± 13.9 years. The most common presentation was the presence of nephrotic syndrome (81.7%) and sub nephrotic proteinuria (10.3%). Microscopic hematuria was detected in one-third of patients. The median estimated glomerular filtration rate (eGFR) was 100.6 mL/min/1.73 m2 (IQR, 75.4–116.3), and median proteinuria was 6000 mg/d (IQR, 3656–9457). Serum C3 and C4 complement levels were decreased in 3.7 and 1.7% of patients, respectively. Twenty-four (2.4%) patients had glomerular crescents in their kidney biopsy samples. Basal membrane thickening was detected in 93.8% of cases under light microscopy. Mesangial proliferation and interstitial inflammation were evident in 32.8 and 55.9% of the patients, respectively. The most commonly detected depositions were IgG (93%), C3 complement (68.8%), and kappa and lambda immunoglobulin light chains (70%). Although renal functions were normal at presentation, vascular, interstitial, and glomerular findings were more prominent on biopsy in hypertensive patients. No significant effect of BMI on biopsy findings was observed. Conclusions Despite some atypical findings, the main features of primary MNP in Turkey were similar to the published literature. This is the largest MNP study to date conducted in Turkish people.

The impact of apical periodontitis, non-surgical root canal retreatment and periapical surgery on serum inflammatory biomarkers.

AimThe aim of the study was to measure serum levels of molecular markers of inflammation in patients undergoing non‐surgical root canal retreatment (Re‐RCT) and periapical surgery (PS) for the treatment of apical periodontitis and to establish if such levels are influenced by the size of apical radiolucencies at baseline and by the treatment outcome.MethodologyA total of 115 participants were recruited (n = 50 Controls, n = 35 Re‐RCT, n = 30 PS). Preoperative periapical radiographs and cone beam CT (CBCT) scans of teeth were taken. Blood was collected from treatment groups at baseline, 3‐, 6‐, and 12‐month post‐treatment and from controls at baseline and 12 months. Serum levels of IL‐1β, IL‐6, IL‐8, TNF‐α, Pentraxin 3, ICAM‐1, VCAM‐1, hs‐CRP, FGF‐23, MMP‐2, MMP‐8, MMP‐9, C3 and ADMA were analysed using multiplex immunoassay and enzyme‐linked immunosorbent assay. Different time points within the same group were compared using Wilcoxon signed‐rank test, and differences between groups were analysed using the Mann–Whitney test. Non‐linear association between different factors was assessed using Spearman's correlation.ResultsPreoperative serum levels of FGF‐23, IL‐1β, hs‐CRP and ADMA were significantly higher in the diseased groups compared with controls (p < .001; p = .008; p < .001; p = .013, respectively). The preoperative size of the radiolucency was associated with increased levels of FGF‐23, IL‐1β and IL‐6. At 3‐months following treatment, IL‐1β, IL‐8, hs‐CRP, C3, MMP‐2 and MMP‐9 levels increased compared with baseline in treatment groups. IL‐1β and IL‐8 further increased at 6 months, whereas FGF‐23, hs‐CRP, C3, MMP2 and MMP‐9 decreased. One‐year post‐treatment, FGF‐23, pentraxin‐3 and ADMA were significantly reduced below baseline levels. At the 1‐year review, CBCT revealed that 25.9% of treated cases completely healed, while 63% were healing, and 11.1% failed. Treatment outcome was found to be influenced by preoperative levels of ADMA and IL‐8 levels at 6 months.ConclusionsBoth symptomatic and asymptomatic apical periodontitis (AP) can contribute to increased levels of molecular markers of inflammation. A further transient inflammatory markers rise after root canal retreatment and apical surgery were demonstrated. Successful endodontic treatment and periapical surgery result in a long‐term reduction in inflammatory marker levels.

Correlation between IgAC3 ratio and oxford score in IgA nephropathy.

Complement activation has an important role in the pathogenesis of IgA nephropathy. To determine the correlation between IgAC3 ratio (IgA/C3) and total Oxford score and predictive value of IgA/C3 in IgA nephropathy. Methods Forty-three patients diagnosed with IgA nephropathy with > 10 glomerular + 1 arteries in biopsy were included in the study. Hematological and biochemical variables of the blood sample taken before the biopsy and total Oxford score were recorded. The study group was divided into two groups as proteinuria ≥ 1g (PU ≥ 1) and proteinuria < 1g (PU < 1). Statistics were carried out with SPSS 22.0 program. p < .05 considered as significant. The mean age of 43 patients was 40.4 (± 11.9) years; 51.2% of them were women. Proteinuria as 1g or more was in 27 of 43 patients, and less than 1g in 16 patients. The serum C3 level was lower in the group with PU ≥ 1 and showed a significant positive correlation with the IgA/C3 total Oxford score. A significant correlation was found between serum IgA/C3 and total Oxford score.

Compartmentalization of Intrarenal Programmed Cell Death Protein 1-Ligand 1 and Its Receptor in Kidney Injury Related to Immune Checkpoint Inhibitor Nephrotoxicity.

BackgroundDue to advances in cancer therapy, immune checkpoint inhibitors (ICIs) are new classes of drugs targeting programmed cell death protein 1-ligand 1 (PD-L1) or its receptor (PD-1) used in many cancer therapies. Acute interstitial nephritis (AIN) is a potential and deleterious immune-related adverse events (irAE) and the most common biopsy-proven diagnosis in ICI-related nephrotoxicity. AIN in patients receiving ICIs is was only seen in cases with tubular PD-L1 positivity, while PD-1 expression is limited to inflammatory cells and also observed in injured kidneys independent of ICI therapy. We have previously described that PD-L1 positivity can also be detected in glomerular and endothelial compartments. We here aimed to describe compartmentalization of renal PD-L1 expression specifically in injured kidneys with confirmed nephrotoxicity related to ICIs, its association with presence of PD-1, and clinical findings.MethodsWe included human kidney samples with AIN related to ICI therapy to describe PD-L1 and PD-1 expression localized to different renal compartments in association with clinical and laboratory parameters.ResultsWe herein report compartmentalization of PD-L1 with tubular positivity in all cases, partially overlapping with glomerular and endothelial PD-L1 positivity. Furthermore, we provide evidence that tubular PD-L1 in ICI-related nephrotoxicity correlates with levels of C-reactive protein (CRP), while glomerular and endothelial PD-L1 positivity with lower serum levels of complement component C4. Interestingly, glomerular PD-L1 correlated with kidney function, while interstitial cell PD-1 positivity specifically with severity of kidney injury. Finally, we provide evidence for signaling pathways associated with intrarenal PD-L1/PD-1 expression.ConclusionOur findings implicate that that AIN related to ICI therapy requires presence of interstitial cells positive for PD-1, and that blocking PD-L1/PD-1 signaling may contribute to nephrotoxicity specifically related to these agents.

Characteristics and renal survival of patients with lupus nephritis with glomerular immunoglobulin G4 deposition: a single-centre retrospective analysis

ObjectiveRenal injury is common in SLE. Immune complex deposition plays an important role in the development of lupus nephritis (LN), while little is known about glomerular IgG4 deposition in patients...

Beneficial effects of re-feeding high α-linolenic acid diets on the muscle quality, cold temperature and disease resistance of tilapia

To investigate the effects of re-feeding high α-linolenic acid (ALA) diets on the muscle quality, cold temperature and disease resistance of the tilapia with nutritional history of soybean oil diets, three experimental diets with linoleic aicd (LA)/ALA ratios at 9 (D1, taking soybean oil as lipid sources), 3 and 1 (D2 and D3, taking soybean and linseed oils as lipid sources) were prepared to re-feed juveniles for 10 weeks, and the growth performance, muscle quality were analyzed. After the re-feeding trial, the fish were fasted for 8 weeks at cold temperature (15°C–20 °C) and then subjected to the Aeromonas hydrophila challenge, and the cold temperature and disease resistance of the fish were evaluated. It was shown that a comparable growth performance was detected among the three dietary groups, while, the high feed efficiency and low viscerosomatic and hepatosomatic index were detected in the D2 and D3 groups compared with the D1 group. In addition, the docosahexaenoic acid (DHA) and n-3 polyunsaturated fatty acid (PUFA) levels of the muscle increased in a parallel pattern with the dietary ALA levels, and the muscular tenderness, adhesiveness, and chewiness were modified substantially in fish fed the diets D2 and D3. After 8-week fasting at cold temperature, the low serum total antioxidant capacity (T-AOC) and malondialdehyde (MDA) levels, and high serum lysozyme (LZM) and C3 levels were observed in the D2 and D3 groups compared with the D1 group. It was also shown that high eicosapentaenoic acid (EPA), DHA, and n-3 PUFA levels were observed in the intestine, liver, and spleen of fish from D2 and D3 groups. Correspondingly, in the fish of the D2 and D3 groups, the mRNA levels of lzm in the liver, intestine, and spleen, and c3 in the intestine and spleen were increased, while the mRNA levels of il-1β, ifn-γ, and tnf-α in the intestine, and ifn-γ, tnf-α in the liver, as well as spleen il-1β, were decreased. Furthermore, the survival at day 15 post-challenge of A. hydrophila in the D2 and D3 groups were higher than those of the D1 group. The results demonstrated that re-feeding high ALA diets were beneficial to the muscle quality, cold temperature and disease resistance in the tilapia, and provide a basis for selecting the dietary lipid sources of tilapia pre-winter feed.

A Cross-Sectional Study to Correlate Serum Complement C3 and C4 Levels With Clinical and Pathological Severity in Cutaneous Small-Vessel Vasculitis.

IntroductionThe role of serum C3 and C4 levels as a marker of disease activity in cutaneous small-vessel vasculitis (CSVV) has been sparsely studied, especially in India. The primary objective was to determine the correlation between clinico-histopathological severity and serum C3 and C4 levels in CSVV. The secondary objective was to determine the association between direct immunofluorescence (DIF) findings and serum C3 and C4 levels and clinico-histopathological findings.MethodThis prospective cross-sectional study included all the clinically diagnosed cases of CSVV that satisfied the pathological criteria for CSVV. A clinical disease activity grade and a histopathological severity grade were calculated in all patients (N=50).ResultsSerum C3 and C4 levels (n=44) were diminished in 4.5% of cases. There was no significant correlation between the serum C3 and C4 levels and the clinical and histopathological severity. DIF was positive in 60.0% of cases (n=45), and IgA was the predominant immune deposit (46.7%). No significant association was detected between the DIF findings and the serum C3 and C4 levels, histopathological severity, and clinical disease activity grade. Positive DIF findings were significantly associated with palpable purpura and cutaneous necrosis. A significant association was detected between gastrointestinal involvement and IgA positivity.ConclusionIn CSVV, serum C3 and C4 may not be used as markers of disease severity, and a positive DIF finding may indicate an underlying gastrointestinal involvement.

α-2,6-sialic acid/IgG anti-dsDNA ratios correlate with human lupus disease activity and possible mechanisms: A pilot study.

To study the association of α2,6-sialic acid (SIA) content in serum IgG anti-dsDNA with human systemic lupus erythematosus disease activity index (SLEDAI) and the effect of sialylated and desialylated (deSIA) IgG anti-dsDNA on lupus B cells. Blood from lupus patients was collected to determine the ratio of SIA in isolated IgG anti-dsDNA over serum IgG anti-dsDNA (SIA/IgG anti-dsDNA) ratios, which were plotted against SLEDAI using a receiver-operating-characteristics curve. Lupus B cells were cultured in vitro with chimeric sialylated IgG anti-dsDNA and its deSIA form. Culture supernatants were assayed for anti-inflammatory IL-10 and SIA/IgG anti-dsDNA ratios, which were compared among different pre-treatment groups using t-tests. The area-under-the-curve (AUC) for anti-dsDNA levels against SLEDAI was 0.791 positively (95% confidence interval [C.I.]: 0.699-0.884) and SIA/IgG anti-dsDNA ratios against SLEDAI yielded an AUC of 0.705 inversely (95% C.I: 0.601-0.809): not significantly different. SIA/IgG anti-dsDNA ratios discriminated significantly between patients without and patients with proteinuria (p = .046). SIA/IgG anti-dsDNA ratios correlated significantly and positively with serum C3c and C4 levels. Pre-treatment with IgG anti-dsDNA and its immune complexes (dsDNA/IgG anti-dsDNA IC) induced higher IL-10 from lupus B cells than medium pre-treatment (most p < .01 from day 2 to day 5 culture). DeSIA IgG anti-dsDNA IC induced lower IL-10 (p < .05) and lower SIA/IgG anti-dsDNA ratios (p < .001) from lupus B cells than medium and dsDNA pre-treatment. α2,6-SIA/IgG anti-dsDNA ratios inversely forecasted SLEDAI scores. Possible mechanisms may be due to the different effects of sialylated and deSIA IgG anti-dsDNA on lupus B cells in terms of IL-10 secretion and SIA/IgG anti-dsDNA ratios.

MO101: Atypical Haemolytic Uremic Syndrome Associated with COVID-19: Case Report

BACKGROUND AND AIMSRenal manifestations are common in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report here the case of a patient with confirmed SARS-CoV-2 infection with the clinical picture of atypical haemolytic uremic syndrome (aHUS).METHODCase reportRESULTSOur case is a 31-year-old man with a nasopharyngeal swab with real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 positive, who was hospitalized in the Clinic of Infectious Diseases. His medical history had a respiratory illness of 7-day evolution characterized by cough, fever, dyspnoea, muscle pain, nausea, vomiting and non-bloody diarrhoea, and decreased urine output with dark colour urine. The chest computed tomography (CT) scan showed few rounded ground-glass opacities.Laboratory tests at admission revealed the following: (i) acute kidney injury stage 3 with a serum creatinine of 3.85 mg/dL (basal value 0.9 mg/dL); serum urea 221 mg/dL. His urinary volume in the first 24 h of hospitalization was 800 mL. (ii) Severe haemolytic anaemia with haemoglobin (Hgb) level of 3.7 g/dL, and peripheral smear showing large number of schistocytes, haptoglobin <10 mg/dL and indirect bilirubin 9.7 mg/dL, direct coombs testing was negative; reticulocyte count 8.9%. (iii) Severe thrombocytopaenia with platelet count of 25 000/µL, prothrombin time 45%, international normalized ratio 1.7, D-dimer 1082 ng/dL and fibrinogen 880 mg/dL.Increased blood levels of enzymes and inflammatory markers were present: lactate dehydrogenase 1867 U/L and protein C reactive 9.1 mg/dL. Electrolyte disturbances characterized by hyperkalaemia, hyperphosphatemia, hypocalcaemia and severe metabolic acidosis. Dynamic changes of laboratory data are presented in Table 1.Table 1.Dynamic changes of laboratory dataLaboratory dataDay 0Day 3Day 7Day 11Day 15Day 19Total serum bilirubin (mg/dL)16.454.8625.8914.69.74.2PT (%)455867889999LDH (U/L)55218671704768667455Serum urea (mg/dL)22121579635645Serum creatinine (mg/dL)3.851.570.70.60.50.6RBC ×106/µL1.221.611.723.233.763.98Hgb (g/dL)3.75.26.58.99.19.3PLTs (K/µL)2533395698178WBC (K/µL)11.224.522.316.214.511.3D-dimer (ng/dL)108246456893423035001800PCR (mg/dL)8.579.117.625.234.451.62Serum fibrinogjen (mg/dL)880647556550450450PT, prothrombin time; LDH, lactate dehydrogenase; RBC, red blood cell; Hgb, haemoglobin; PLT, platelet cell count; WBC, white blood cell; PCR, protein C reactive.The usual liver panel tests, alkaline phosphatase, γ-glutamyl transferase and albuminemia were normal. Toxic hepatitis was excluded. Hepatobiliary and spleen imaging (ultrasonography) was normal.ELISA serologic tests for HIV, hepatitis B, hepatitis C virus and cytomegalovirus were negative. Serological and virological tests for hepatitis A, B, C, HIV and CMV were negative. Stool was negative for Shiga toxin-producing Escherichia coli (STEC).The results of antinuclear antibodies and anti-smooth-muscle antibodies were negative, C3 serum level was mildly depressed (82 mg/dL; normal range 88–201 mg/dL) and C4 serum level was normal (20 mg/dL; normal range 10–44 mg/dL). ADAMTS13 activity was 90% on day 10.He was treated with broad spectrum antibiotics, intravenous dexamethasone and supportive therapy. One week from admission, renal function recovered, and 1 week after intravascular haemolysis and thrombocytopaenia recovered. The patient was hospitalized for 21 days.CONCLUSIONClose monitoring and early intervention can help for a better outcome of SARS-CoV-2 patients complicated with aHUS.

MO231: Comparison of Dominant and Non-Dominant C3 Deposition in Primary Glomerulonephritis

Abstract BACKGROUND AND AIMS Alternative complement pathway (AP) dysregulation plays a key role in glomerulonephritis (GN) and is associated with C3 deposition. Herein, we examined pathological and clinical differences between cases of primary GN with C3-dominant (C3D-GN) and non-dominant (C3ND-GN) deposition. METHOD We extracted primary GN data from the Korean GlomeruloNEphritis sTudy (KoGNET). C3D-GN was defined as C3 staining two grades greater than C1q, C4 and immunoglobulin via immunofluorescence analysis. Data between groups were age- and sex-matched (each group, n = 61). RESULTS The C3D-GN group exhibited higher serum creatinine (P = .027), greater prevalence of estimated glomerular filtration rates &amp;lt; 60 mL/min/1.72 m2 (P = .009), higher C-reactive protein levels (P = .003) and lower serum C3 levels (P = .018). Serum albumin, urine protein/creatinine ratio, number of patients who progressed to end-stage renal disease and mortality were comparable between groups. Interstitial fibrosis and tubular atrophy were greater in the C3D-GN group (P = .0027 and .005, respectively) than in the non-C3GN group. C3 deposition was dominant in the former group (P &amp;lt; .001), in parallel with increased subendothelial deposition (P = .003). CONCLUSION Greater progression of renal injury and inflammation occurred in patients with C3D-GN than with C3ND-GN, potentially owing to AP dysregulation.