Serum C3 Research Articles

Disparities between IgG4-related kidney disease and extrarenal IgG4-related disease in a case\u2013control study based on 450 patients

We aimed to compare the demographic, clinical and laboratory characteristics between IgG4-related kidney disease (IgG4-RKD+) and extrarenal IgG4-related disease (IgG4-RKD−) in a large Chinese cohort, as well as describing the radiological and pathological features of IgG4-RKD+. We retrospectively analyzed the medical records of 470 IgG4-related disease (IgG4-RD) patients at Peking University People’s Hospital from January 2004 to January 2020. The demographic, clinical, laboratory, radiological and pathological characteristics between IgG4-RKD+ and IgG4-RKD− were compared. Twenty IgG4-RD patients who had definite etiology of renal impairment including diabetes, hypertension and etc. were excluded. Among the remained 450 IgG4-RD patients, 53 were diagnosed with IgG4-RKD+ . IgG4-RKD+ patients had older age at onset and at diagnosis. Male to female ratio of IgG4-RKD+ patients is significantly higher. In the IgG4-RKD+ group, the most commonly involved organs were salivary gland, lymph nodes and pancreas. It was found that renal function was impaired in approximately 40% of IgG4-RKD+ patients. The most common imaging finding is multiple, often bilateral, hypodense lesions. Male sex, more than three organs involved, and low serum C3 level were risk factors for IgG4-RKD+ in IgG4-RD patients. These findings indicate potential differences in pathogenesis of these two phenotypes.

Effects of andrographolide on lipopolysaccharide‐induced serum biochemical indices, immune responses and intestinal inflammation related to gene expression of Monopterus albus

An 8-week trial investigated how andrographolide effected lipopolysaccharide (LPS)-induced serum biochemical indices, immune responses and the intestinal inflammatory response of Monopterus albus. The study included control and andrographolide groups (150 mg/kg andrographolide) with three replicates per group. Samples were taken 0, 3, 6, 12, 24 and 48 h after LPS injection. The results showed that the levels of GLU, COR, AST, ALT, IgM, LZM, AKP, C3 and C4 in serum showed an initial increasing that then decreased. Compared with that of the control group, the levels of serum LZM, AKP, IgM, C3 and C4 in the andrographolide group increased quicker after LPS injection, while the levels of GLU, COR, AST and ALT increased more slowly; further, these indices recovered to normal levels quicker. The expression of several genes in the intestine first increased and then decreased after LPS injection. Compared with that of the control group, il-10, tgf-β1, tgf-β2 and tgf-β3 gene expression in the andrographolide group increased quicker after LPS injection, while that of il-1β, il-8, il-12β, nf-κb, tlr-3, tlr-7 and tlr-8 increased more slowly; these indices recovered to normal levels more quickly. In conclusion, LPS injection induced immune stress and inflammatory response in M. albus. Dietary supplementation with 150 mg/kg andrographolide effectively alleviated these responses.

Dose-effect relationship between serum polycyclic aromatic hydrocarbon adducts and serum complements among children in a city of East China

Objective: To investigate the dose-response relationship between serum polycyclic aromatic hydrocarbon adducts and serum complement C3 and C4 levels among children from a city in East China. Methods: In September 2016, two boarding schools in the air pollution exposure area and the control area (beyond the upwind of 30 km in the air pollution exposure area) in a city in East China were selected as the research site, and the eligible school-age children were recruited as the research objects. A total of 273 children were included, including 163 in the exposure group and 110 in the control group. The annual air pollutant data (PM2.5, PM10 and NO2) of the two regions during the study period were collected. The exposure level of tobacco was evaluated by cotinine in urine. The levels of serum complement C3 and C4 were determined by automatic biochemical analyzer. The serum anti-7, 8, -dihydrodiol-9, 10-epoxide benzo[a]pyrene (BPDE)-albumin adduct levels were detected by ELISA. Linear regression model was used to explore the dose-response relationship between BPDE-albumin adducts and serum complement C3 and C4. Results: The age of 273 subjects was (13.67±0.37) years old, including 165 boys (60.4%). The average annual exposure levels of PM2.5, PM10 and NO2 and the level of serum BPDE-albumin adducts in the exposure group were higher than those in the control group (P<0.05). The results of linear regression model analysis showed that after adjusting age, sex, BMI z-score and urinary cotinine level, when the serum BPDE-albumin adduct level increased by 10%, the serum complement C4 level decreased by 1.2% (P=0.017). After adjusting age, BMI z-score and urinary cotinine level, for every 10% increase in serum BPDE-albumin adduct level in boys, the serum complement C4 level decreased by 1.68% (P=0.024). After adjusting age, sex and BMI z-score, the levels of serum complement C3 and C4 decreased by 1.31% and 3.57% respectively for every 10% increase in serum BPDE-albumin adducts among children in the urinary cotinine detection group (P<0.05). Conclusion: There is a significant dose-response relationship between serum BPDE-albumin adducts and the complement C4 among children.

The role of PD-1/PD-Ls in the pathogenesis of IgG4-related disease.

To investigate the role of programmed cell death protein 1 (PD-1) and its two ligands, PD-L1 and PD-L2, in the pathogenesis of IgG4-related disease (IgG4-RD). Patients with IgG4-RD (n = 43) and healthy controls (n = 34) were recruited. Expression levels of PD-1, PD-L1 and PD-L2 in plasma, submandibular gland and T cell subsets were determined by ELISA, immunohistochemistry and flow cytometry. Naïve T cells were stimulated with or without PD-L1/PD-L2 or anti-PD-L1/anti-PD-L2 for 7 days and the proportion of CD4+CD25+ Treg cells was detected by flow cytometry. The expression of PD-1, PD-L1 and PD-L2 in the plasma, submandibular gland and on the surface of Treg cells was increased in IgG4-RD patients. Plasma soluble (s)PD-1 was positively correlated with serum IgG, IgG1, IgG3, IgG4, IgG4-RD responder index and numbers of organs involved, and negatively correlated with serum IgM, IgA, C3 and C4. Plasma sPD-L2 was positively correlated with serum IgG1, and plasma sPD-L1 was positively correlated with sPD-L2 and negatively correlated with C3. Stimulation of PD-L1 but not PD-L2 promoted the differentiation of naïve T cells from IgG4-RD patients into CD4+CD25+ Treg cells. Plasma concentrations of sPD-1, sPD-L1 and sPD-L2 were significantly increased in patients with IgG4-RD, and the expression of PD-1 and PD-L2 on Treg cells was upregulated. PD-1-PD-L1 can promote the differentiation of naïve T cells into Treg cells and thus participate in the pathogenesis of IgG4-RD.

Pharmacokinetics and pharmacodynamics of single and multiple-dose levamisole in belugas (Huso huso): Main focus on immunity responses

The pharmacokinetics of levamisole were determined in the belugas after single intravascular (IV), and single and multiple-dose oral by feed administrations. Also, the effect of levamisole (LVM) on the stress and immune responses of belugas were assessed. One hundred-fourteen healthy belugas in 4 different groups received single LVM administration at the doses of 50 and 100 mg/kg via IV and oral routes. A separate group of 24 belugas were administered oral LVM at the dose of 100 mg/kg for 5 days. Blood samples were collected at different time points after administrations to measure plasma concentrations of LVM by a validated high-performance liquid chromatography (HPLC) assay. For immunological evaluations, a total of 126 belugas received 50 and 100 mg/kg LVM via medicated feed for 5 days or served as the control without any medication; blood samples were recovered on day 0, 1, 3, 5, 7, 10, and 14 to measure hemolytic activity of the complement system (HAC50), serum lysozyme activity, serum antibacterial activity, glucose, cortisol, total protein, albumin and C3 contents. In the single-dose administration, quantified LVM concentrations were dose-dependent and the oral bioavailability was in the range of 43.2–49.6%. In the multiple-dose administration, the peak plasma concentration at the steady state was 45.2 mg/ml, and accumulation ratio was calculated as 3.6. In the immunological study, LVM especially at the dose of 100 mg/kg increased HAC50, lysozyme and antibacterial activity in the sera of treated fish. No significant effect of LVM on glucose and albumin content was observed, but cortisol levels decreased and C3 content was increased, more significantly by LVM at the dose of 100 mg/kg. Our results indicate that LVM is well absorbed after oral administration and reached to concentrations that can affect stress indicators and improve immune responses in belugas.

Serum complement levels as prognostic marker for monitoring treatment response in lupus nephritis

Background: Lupus nephritis (LN) is one of the most common and serious manifestations of systemic lupus erythematosus (SLE) that causes significant morbidity and mortality. Certain biomarkers for LN are sometimes able to assess treatment response in lupus nephritis. This study aimed to compare serum complement levels (C3 and C4) as markers of treatment response of LN and their relation to the LN class in renal biopsy.&#x0D; Methods: This prospective observational study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2018 to August 2019. Twenty seven patients who were diagnosed with LN after kidney biopsy were included in this study. Serum complement levels (C3 and C4), 24 hours urinary total protein (24-hr UTP) and anti-double-stranded DNA (anti-ds DNA) were measured in all patients at baseline, 3 months and 6 months after treatment initiation. These biomarker values before and after treatment were compared between the proliferative and non-proliferative LN patients.&#x0D; Results: Serum C3 levels were significantly different between patients with proliferative LN (Class III and Class IV) and non-proliferative LN (Class V) at baseline (0.47 ± 0.32 g/l versus 0.89 ± 0.43 g/l, p=0.009) and levels changed significantly 6 months after treatment initiation (p&lt;0.001) and likewise for serum C4 levels (0.10 ± 0.06 g/l versus 0.24 ± 0.26 g/l, p=0.040). The values of 24-hr UTP and anti-ds-DNA were significantly different 6 months after treatment with p value &lt;0.05 in both groups but C3 (p&lt;0.001) and renal Systemic Lupus Erythematosus Disease Activity Index (rSLEDAI) (p&lt;0.001) were only significant in the proliferative group. On the other hand, after 6 months treatment, C4 levels became relatively higher but that was not significant in both groups (p&gt;0.05).&#x0D; Conclusion: After 6 months of treatment, serum C3 and C4 levels increased towards normal in both LN groups. Serum C3 and C4 levels in patients with LN correlate with disease activity. Therefore, serum complement (C3 and C4) levels may be utilized as serological biomarkers for treatment response of LN.&#x0D; Birdem Med J 2021; 11(2): 97-102

C3 glomerulonephritis associated with ANCA positivity: a case report

BackgroundC3 glomerulopathy (C3G) is a recent disease classification that is characterized by the presence of glomerular deposits (composed of C3) in the absence of significant amounts of immunoglobulin and comprises dense deposit disease and C3 glomerulonephritis (C3GN). Most C3GN manifests as membranoproliferative, mesangial proliferative glomerulonephritis patterns via light microscopy. Pure membranous nephropathy (MN)-like glomerular lesions are rare manifestations of C3GN. Anti-neutrophil cytoplasmic antibodies (ANCAs) are also seldomly reported to be positive in C3GN. Herein, we report the case of a C3GN patient presenting with an MN-like glomerular pattern with ANCA positivity.Case presentationA 68-year-old woman was admitted to a local hospital with elevated serum creatinine for two weeks. Laboratory tests showed a hemoglobin level of 85 g/L. Urinalysis was positive for 2 + protein and 360 RBCs/HPF. Blood biochemistry analysis revealed the following concentrations: albumin, 30.3 g/L; globulin, 46.2 g/L; blood urea nitrogen, 19.9 mmol/L; and serum creatinine, 234 µmol/L. The serum C3 level was 0.4950 g/L, and the serum C4 level was 0.1050 g/L. The direct Coombs test was positive. Serologic testing for ANCA revealed the presence of p-ANCA (1:10) by indirect immunofluorescence microscopy assay, as well as the presence of PR3 1.2 (normal range < 1) and MPO 3.5 (normal range < 1) by enzyme immunoassay. Renal biopsy sample pathology showed 2/6 cellular crescents and thickened glomerular basement membranes. Immunofluorescence testing revealed only diffuse, finely granular depositions of C3 along the glomerular capillary walls in frozen and paraffin-embedded tissue sections. Electron microscopy demonstrated the presence of subepithelial electron-dense deposits, similar to those that are observed in membranous nephropathy. Corticosteroid and cyclophosphamide were administered, with a subsequent improvement in renal function.ConclusionsWe present the rare case of a patient with MN-like C3GN with ANCA positivity. C3GN with ANCA positivity may be represented by more crescents, severe renal dysfunction and more extrarenal manifestations. More cases are needed to elucidate the clinicopathologic features and optimal treatments of these patients.

Association of antiphospholipid antibodies with clinical activity and renal pathological activity in patients with lupus nephritis.

This study aimed to investigate the association of antiphospholipid antibodies (aPL) with clinical activity and renal pathological activity in patients with lupus nephritis (LN). Levels of anticardiolipin () antibodies, anti-β2-glycoprotein I (anti-β2-GPI) antibodies and lupus anticoagulant (LAC) were measured, and other clinical and pathological data were also obtained during the same period before renal biopsy. A total of 83 patients with LN were included in this study, 40 patients (48.2%) in the s positive group and 43 patients in the aPL negative group. LN patients with positive aPL had significantly higher SLEDAI (p = 0.012), more hematuria (p = 0.043), lower serum C3 (p = 0.003) and C4 (p = 0.014), and a higher pathological activity index (p = 0.012), more micro-thrombosis (p = 0.046) and more C3 deposits (p = 0.038) in the glomerulus than patients with negative aPL The level of IgG- was significantly correlated with SLEDAI and serum level of C3 (r = 0.44, p < 0.001; r = -0.39, p = 0.003, respectively). The level of IgM- was significantly correlated with SLEDAI, and serum levels of C3 and C4 (r = 0.27, p = 0.014; r = -0.22, p = 0.041; r = -0.23, p = 0.035, respectively). Our work suggests that aPL, especially, are correlated with both clinical activity and renal pathological activity in patients with LN.

Clinical characteristics and outcome of IgG4-related disease with hypocomplementemia: a prospective cohort study

BackgroundImmunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic, immune-mediated, and fibro-inflammatory disease. Hypocomplementemia was found in part of IgG4-RD patients especially in the setting of active disease.ObjectivesThis study aimed to clarify the clinical features, treatment efficacy, and outcome in IgG4-RD patients with hypocomplementemia.Methods312 IgG4-RD patients were recruited in our prospective cohort conducted in Peking Union Medical College Hospital. Patients were divided into hypocomplementemia group and normal complement group according to serum C3 and C4 levels measured at baseline before treatment. Low serum C3 levels (< 0.73 g/L) and/or C4 levels (< 0.10 g/L) were defined as hypocomplementemia. Demographic data, clinical characteristics, laboratory parameters, treatment, and outcome of two groups were analyzed and compared.ResultsHypocomplementemia was identified in 65 (20.8%) cases of untreated IgG4-RD patients at baseline. The average age of hypocomplementemia group was 55.85 ± 10.89 years, with male predominance (72.3%). Compared with normal complement group, patients with hypocomplementemia were likely to have more involved organs, higher IgG4-RD responder index (IgG4-RD RI), and higher laboratory parameters such as counts of eosinophils, inflammatory markers, immunoglobulin G (IgG), IgG1, IgG3, IgG4, and IgE. In addition, lymph nodes, lacrimal gland, submandibular gland, parotid gland, paranasal sinus, bile ducts, and prostate gland were more commonly affected (p < 0.05). Serum C3 and C4 showed a significant positively correlation with each other. Both C3 and C4 were negatively correlated with the number of involved organs, IgG, IgG3, IgG4, and IgG4-RD RI, as well as positively correlated with IgA and hypersensitive C reactive protein (hsCRP). 64 (98.5%) patients responded quickly to initial therapy at a 3-month follow-up. Fifteen (23.1%) patients relapsed during follow-up with mean recurrence time of 14.2 ± 13.8 months. Compared with normal complement group, there was no significant difference of relapse rate in two groups (P = 0.401).ConclusionsClinical characteristics of IgG4-related disease with hypocomplementemia differ from normal complement group. Serum C3 and C4 at baseline before treatment could be biological markers for disease activity. IgG4-RD with hypocomplementemia responded well to treatment and had no significant difference of relapse rate in IgG4-RD with normal complement.

ASSESSMENT OF THE SERUM LEVEL OF COMPLEMENT C3 AND C4 IN CHRONIC VIRAL HEPATITIS C INFECTION AND THEIR CORRELATION WITH RESPONSE TO DIRECT ACTING ANTI-VIRAL AGENTS

Background: The interactions between hepatitis C Virus (HCV) and the host immune system have a major role in HCV pathogenesis. Objective: To estimate complement C3 and C4 serum levels in patients with chronic HCV patients and to correlate its levels with response to directly acting anti-viral agents (DAAs) in those patients. Patients and methods: The study included 80 individuals classified into two groups: Group (I): 40 patients with chronic HCV infection, Group (II): Control group which included 40 healthy individuals. Measurement of the level of complement C3 and C4 has done by nephelometry immunoassay before and after treatment with DAAs. Results: All patients with chronic HCV infection in group (I) showed significant reduction in serum levels of complement C3 and C4 compared to the control group (II). Moreover, those patients who treated with DAAs showed significantly higher levels of C3 and C4 when compared to chronic HCV patients before treatment with DAAs. Conclusion: Serum levels of complement C3 and C4 serum may be used in the follow up of the course of the disease and may be used as a predictor for the response to treatment with DAAs.

RENAL HISTOPATHOLOGICAL PROFILE IN PATIENTS WITH SILENT LUPUS NEPHRITIS

Background: Silent lupus nephritis (SLN) is a life menacing consequence of systemic lupus erythematous (SLE). This condition is characterized by pathological impairment of the kidney in the obscurity of clinical or laboratory manifestations. Objective: To reveal the existence of SLN along with the potential differences between overt lupus nephritis (OLN) and SLN among a sample of Egyptian patients based on histopathological assessment. Patients and Methods: It is a prospective case-control study which was performed at nephrology units, internal medicine department, Elhussein and Sayed Galal university hospitals, faculty of medicine, Al-Azhar University, Cairo, Egypt, throughout the entire period April 2016 to November 2019. Patients aged more than 18 years (216 months) and fulfilled at least 4 of the American College of Rheumatology criteria for the classification of systemic lupus erythematosus (SLE) were enrolled in the current study. Patients were further assorted into two groups; patients with SLN and those with OLN. Patients were subjected to the following investigations: 1.Complete blood count, using Coulter counter Max-M (Coulter Cooperation, Florida, USA) 2.Erythrocyte sedimentation rate, (Wester green method) (Ref: < 20mm/hr) 3.S. Albumin, S. Creatinine. Albumin/Creatinine ratio. Creatinine clearanc & eGFR using the Modification of Diet in Renal Disease (MDRD) formula. 4. Liver function tests. 5. Coagulation profile. 6. Urine analysis (Fresh morning midstream urine) to exclude infection. 7. Quantitative assessment of proteinuria by Pr/creat. Ratio (Ref. <0.2). Assessment of auto-antibodies and complement system: Autoantibodies to ds-DNA, RNP. SSA, SSB, Sm and Scl-70, C4 and C3 serum levels were assessed in all of the included patients. In particular, the titer of anti-dsDNA antibodies was evaluated by enzyme- Radiological evaluation: Patients were subjected to pelvi-abdominal ultrasound in order to obtain valuable data about the morphological appearance of the kidney and to detect any urological abnormality. Renal biopsy: Percutaneous renal biopsy was carried out under local anesthesia. Results: An overall 40 patients with SLE who developed lupus nephritis were enrolled in the current study. Among them, 20 patients had OLN, whereas 20 patients were SLN. Based on ISN/RPS Classification, stage II was the predominant stage, 13 patients, among patients with SLN, whilst stage V was the predominant stage among the OLN patients. Additionally, five and three patients were stage III among the SLN and OLN groups, respectively. Furthermore, the presence of RBCs Cast (r=0.479, P=0.032) in urine and decreased levels of complement (r=0.676, P=0.001) showed a statistically significant positive correlation with the high grades of lupus nephritis among SLN group. Conclusion: Patients with SLE should be subjected to close follow up evaluation and renal biopsy for early detection of SLN to determine the activity, severity, and chronicity of LN.

POS-202 ATYPICAL HEMOLYTIC UREMIC SYNDROME: A RARE CAUSE OF MALIGNANT HYPERTENSION AND ACUTE RENAL FAILURE IN ADULT

Atypical hemolytic uremic syndrome (aHUS) is a form of complement-mediated thrombotic microangiopathy mainly characterized by excessive activation of alternative complement pathway activation. This occurs due to mutation in the complement regulatory proteins or by acquired neutralizing antibodies to these complement regulatory proteins. It is characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. It usually has a poor prognosis in the absence of prompt recognition and treatment, with more than 50% of the patients progressing to end stage renal disease. Case report- A 21 year old male presented to emergency with sudden onset headache, blurring of vision and multiple episodes of vomiting. There was no history of diarrhea or dysentery in recent past.Thorough examination was done and investigations were performed. On examination, patient had pallor and elevated blood pressure of 200/100 mmHg. Relevant findings on investigations was anemia (hemoglobin: 8.9g/dl), thrombocytopenia (platelet count: 98000cells/cu.mm) and deranged renal function tests (BUN: 156, Creatinine: 7.4mg/dl). LFT showed raised total bilirubin: 2.4mg/dl with direct fraction 0.3mg/dl. LDH and uric acid were also raised(1131U/L and 9.5mg/dl respectively). Urine routine showed trace proteinuria and urine for active sediment was negative for cast. Ultrasound of bilateral kidneys showed normal echogenecity, normal size and a maintained corticomedullary differentiation with a normal renal artery Doppler study. Peripheral smear was suggestive of Normocytic normochromic anemia with occasional target cells, elliptical cells and fragmented RBC’s with a raised reticulocyte count of 6.6. With these reports, a probable diagnosis of hemolytic uremic syndrome was considered. Stool cultures for shiga toxin producing E.coli was negative. The patient had uncontrolled hypertension despite three antihypertensives, thrombocytopenia and renal failure worsened further and patient was initiated on dialysis. Kidney biopsy was done in view of rapidly progressing renal failure which showed prominent subendothelial edema with blood vessels showing mucoid edema with near complete obstruction of lumen of medium sized vessels suggestive of thrombotic microangiopathy with acute tubular necrosis (figure1). Serum C3 levels were significantly on lower side with near normal C4 levels. ADAMTS13 levels were within normal limits. Hence a diagnosis of atypical hemolytic syndrome was finally considered .The test for complement factor H antibody was negative. However further confirmatory investigations like genetic analysis of complement regulatory genes were unavailable. Patient was also started on daily sessions of plasma exchange therapy as eculizumab was not available due to financial constraints. Over next 10 days patients clinical condition started to stabilize with improvement in renal function, anemia and platelet count. Patient was discharged and advised to follow up with monitoring of renal function tests. In patients with hypertensive crisis, acute renal failure and thrombocytopenia, aHUS should be considered. Timely recognition of disease and prompt treatment is essential for favourable outcome. In the face of non-availability of eculizumab, plasmapheresis can be considered as initial treatment option.

Serum Immunoglobulin Levels, Complement Components 3 and 4, HLA-B27 Allele and Spondyloarthropathy in Patients with Non-Infectious Anterior Uveites.

To identify the relationship between serum immunoglobulin levels, complement components 3 and 4, the presence of the HLA-B27 allele and diagnosis of spondyloarthropathies in patients with non-infectious anterior uveitis. The participants were 197 patients with a non-infectious anterior uveitis. The concentrations of serum immunoglobulins, and C3 and C4 proteins of the complement were determined by turbidimetry. The personal history of suspected immunodeficiency, ophthalmological complications, arthralgia, family history of spondyloarthropathies and the presence of the HLA-B27 allele were collected. A family history of spondyloarthropathy, axial arthralgias, and ophthalmological complications were more frequent in HLA-B27 positive patients (P=.0005, P≤.0001, and P≤.0001, respectively) and in patients with spondyloarthropathy diagnoses (P≤.0001, P≤.0001, and P≤.0001, respectively). A personal history of recurrent sepsis, and gastrointestinal abnormalities was associated with the presence of the HLA-B27 allele (P≤.0001, and P=.0240, respectively) and with the diagnosis of spondyloarthropathy (P=.0492, and P=.0017, respectively). IgG decrease was observed (χ2=18.5, OR 5.03, 95% CI 2.32-10.89; P=.0001) and IgM (OR 7.13, 95% CI 1.40-36.4; P=.0128) in patients positive for the HLA-B27 allele and in patients with a diagnosis of spondyloarthropathies (P=.0364 and P=.0028, respectively). The decrease of C3 proteins (OR 4.82; CI 95% 1.35-17.11; P=.0328) and C4 (OR 9.09; CI 95% 2.13-38.88; P=.0074) were associated with a spondyloarthropathies diagnosis. Patients with non-infectious anterior uveitis, positive for the HLA-B27 allele and diagnosed with spondyloarthropathies have alterations in serum immunoglobulin levels and complement components 3 and 4, which could contribute to the perpetuation and worse clinical course of this disease.

Effects of age on immune function in broiler chickens

BackgroundThere are many diseases in poultry, many of which are caused by poor immune function. It is not clear how cytokines and various immune cell functions change with age in modern broilers. The purpose of this study was to explore the patterns of development of the immunity of the broiler chickens in cage.ResultsThe results showed that there were 3 development patterns of immunity in the broiler chickens. The first pattern was Down-Up. Cytokines and some immune indicators first decreased and then increased, and the lowest levels of immunity basically occurred from d 6 to 13. The second pattern was Up-Down, and from d 30 to 34, the highest levels of non-specific cellular immunity components, such as the peripheral blood mononuclear macrophage ratio, specific cellular immunity components, such as the peripheral blood helper T (Th) cell ratio and T cell and B cell proliferation activity, and mucosal immunity components, such as the ileal CD4, TGF-β1 and IgA mRNA levels, were observed. The third pattern was Up-Up, and the levels of the non-specific cellular immunity components, such as the serum nitric oxide (NO), C3 and C4 levels, the specific cellular immunity components, such as the spleen index, peripheral blood IL-2, IFN-γ/IL-4, cytotoxic T (Tc) cell ratio, and splenic NF-κB mRNA levels, the humoral immunity components, such as the serum IgG level, the mucosal immunity components, such as the ileal MHC-II, CD3d, TCRβ subunit, TCRζ subunit, IFN-γ, pIgR mRNA and ileal mucosa sIgA levels, were continuing to increase from d 1 to 34.ConclusionsIt could be concluded that the immune system and its function have not developed well in the broiler chickens d 6 to 13 and that the immune system does not mature until d 30 to 34 in the broiler chickens in cages. It is necessary to enhance the immune function of the broiler chickens through nutritional measures from d 1 to 30.

Serum immunoglobulin levels, complement components 3 and 4, HLA-B27 allele and spondyloarthropathy in patients with non-infectious anterior uveites

ObjectiveTo identify the relationship between serum immunoglobulin levels, complement components 3 and 4, the presence of the HLA-B27 allele and diagnosis of spondyloarthropathies in patients with non-infectious anterior uveitis. Materials and methodsThe participants were 197 patients with a non-infectious anterior uveitis. The concentrations of serum immunoglobulins, C3 and C4 proteins of the complement were determined by turbidimetry. The personal history of suspected immunodeficiency, ophthalmological complications, arthralgia, family history of spondyloarthropathies and the presence of the HLA-B27 allele were collected. ResultsA family history of spondyloarthropathy, axial arthralgias, and ophthalmological complications were more frequent in HLA-B27 positive patients (P=.0005, P≤.0001, P≤.0001 respectively) and in patients with spondyloarthropathy diagnoses (P≤.0001, P≤.0001, P≤.0001 respectively). A personal history of recurrent sepsis, and gastrointestinal abnormalities was associated with the presence of the HLA-B27 allele (P≤.0001, P=.0240 respectively) and with the diagnosis of spondyloarthropathy (P=.0492, P=.0017 respectively). IgG decrease was observed (χ2=18.5, OR=5.03, 95% CI=2.32–10.89, P=.0001) and M (OR=7.13, 95% CI=1.40−36.4; P=.0128) in patients positive for the HLA-B27 allele and in patients with a diagnosis of SpA (P=.0364 and P=.0028 respectively). The decrease of C3 proteins (OR=4.82; CI 95%=1.35–17.11; P=.0328) and C4 (OR=9.09; CI 95%=2.13–38.88; P=.0074) were associated with a spondyloarthropathies diagnosis. ConclusionsPatients with non-infectious anterior uveitis, positive for the HLA-B27 allele and diagnosed with spondyloarthropathies have alterations in serum immunoglobulin levels and complement components 3 and 4, which could contribute to the perpetuation and worse clinical course of this disease.

Thrombotic microangiopathy versus class IV lupus nephritis in systemic lupus erythematosus.

Kidney involvement is common in patients with systemic lupus erythematosus (SLE). This study investigates the clinical and prognostic characteristics of thrombotic microangiopathy (TMA) compared to class IV lupus nephritis in SLE patients. A retrospective review of patients who underwent kidney biopsy, with a primary diagnosis of SLE and TMA between June 2006 and September 2018 was conducted. Those patients were subsequently compared to patients with class IV lupus nephritis between January 2018 and December 2018. Demographics, laboratory, and serological data at the time of biopsy were abstracted. Among 214 SLE patients records screened, 27 were included in the final analysis. Eight patients had lupus-related TMA without evidence of active lupus nephritis, while 19 patients had class IV lupus nephritis without evidence of TMA. TMA patients had significantly higher lactate dehydrogenase levels (718 ± 499 vs. 264 ± 107.7 U/L, p = 0.009), serum C3 (100.6 ± 39.3 vs. 65.8 ± 27mg/dL, p = 0.049), white blood cell count (14743.8 ± 7933.3 vs. 5807.9 ± 2053.2 × 10E3/uL, p < 0.001), and total bilirubin (0.8 ± 0.5 vs. 0.3 ± 0.1mg/dL, p = 0.007) in addition to significantly lower platelet counts (158.4 ± 88.6 vs. 240.3 ± 100.3 × 10E3/uL, p = 0.03), and haptoglobin (68.8 ± 116.1 vs. 166.8 ± 95.4mg/dL, p = 0.03). After a median follow-up time of 53 weeks, 3 patients with TMA were dialysis-dependent (37.5%), compared with none in class IV lupus nephritis patients (p = 0.002). TMA-associated SLE has worse prognosis compared to class IV lupus nephritis. An array of laboratory and pathological findings may be of value in discriminating between those two entities.

Mesangial C3 deposition and serum C3 levels predict renal outcome in IgA nephropathy.

Complement activation plays an important role in the pathogenesis of IgA nephropathy (IgAN). We aimed to evaluate the relationship between mesangial C3 deposition and histologic lesions and to investigate the role of mesangial C3 deposition and serum C3 reduction in predicting renal outcome in IgAN children. We performed a retrospective cohort study in children with biopsy-proven IgAN. Mesangial C3 deposition (< 2+ vs. ≥ 2+) was detected by the immunofluorescence. Histopathologic kidney grades were determined by the Oxford classification. A decreased serum C3 concentration (hypoC3) was defined when C3 < 90mg/dl. The endpoint was composite kidney outcome with either a 30% decline in glomerular filtration rates from baseline or kidney failure during the follow-up period. A total of 98 children were analyzed. Mesangial hypercellularity (M) was an independent factor associated with mesangial C3 deposition (HR 3.267; 95% CI 1.028-10.389; P = 0.045). After a median follow-up period of 25months (interquartile range 18-36months), 6 (6.1%) children reached the endpoint. Compared with other children, a significantly higher proportion of children with composite kidney outcomes had mesangial C3 deposition ≥ 2+ and hypoC3 (3.4% versus 27.3%, P = 0.002). After adjustment for clinicopathologic risk factors, mesangial C3 deposition ≥ 2+ and hypoC3 were associated with renal outcome (HR 9.772; 95% CI 1.264-75.518; P = 0.029). Mesangial C3 deposition was associated with M in IgAN. Mesangial C3 deposition and hypoC3 were risk factors for renal outcome in children with IgAN.

Early Decline of Neuron-Specific Enolase during Neuroblastoma Chemotherapy is a Predictive Factor of Clinical Outcome

High risk neuroblastoma (HR-NB) remains one of the most difficult-to-treat pediatric cancers. However, although current risk-stratification is based on multiple pretreatment criteria, HR-NB remains a significant heterogeneity. We examined 60 patients with HR-NB for a median follow-up time of 28 months. We examined the serum neuronspecific enolase (NSE) levels of each chemo cycle, using the survival receiver operating characteristic (survivalROC) method to assess the prognostic power of NSE levels at variant chemo points. We demonstrated that serum NSE was associated with systemic tumor burden. NSE after the third chemo cycle (C3) (C3NSE) was significantly higher in patients who eventually showed cancer relapse or progression. C3NSE had independent prognostic significance for event-free survival (EFS) but not for overall survival (OS) in multivariate cox analysis. SurvivalROC prompted that the C3NSE is a prognostic marker of HR-NB, which had good discrimination for 2- and 3-year EFS with AUC 0.734 and 0.729, respectively. However, its prognositc value for 2- and 3- year OS declined progressively. C3 is the optimal point to predict EFS. Patients whose C3 serum NSE remain at higher level need to undergo more intensive treatment as early as possible to resist recurrence.

Markers of Bile Acid Metabolism in Pediatric Diarrhea Predominant Irritable Bowel Syndrome and Healthy Controls.

Excessive fecal bile acids in adults have been associated with diarrhea-predominant irritable bowel syndrome (IBS-D), but their role in pediatric IBS-D is unknown. Serum markers including 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor-19 (FGF-19) were validated in adults to detect bile acid diarrhea (BAD) compared to 48-hour fecal bile acid collection (48FBA). Our aims were to assess fasting serum C4 and FGF-19 and 48FBA in a pediatric population, to compare measurements in IBS-D patients and healthy controls (HC), and to determine the prevalence of BAD among children with IBS-D. Using a cross-sectional design, 26 patients with IBS-D and 56 HC were recruited in two pediatric tertiary care centers. Fasting serum C4 and FGF-19 and 48FBA were obtained. Participants completed a 7-day bowel diary coinciding with stool collection. Associations were analyzed using Spearman correlations. Mean age was 14.7 ± 2.5 years (42.3% female) in IBS-D and 12.6 ± 2.4 years (39.3% female) in HC. There was a significant correlation of C4 with 48FBA (r = 0.48, P < 0.05) and an inverse association with FGF-19 (r = -0.43, P < 0.05). No significant differences were noted in C4 (P = 0.32), FGF-19 (P = 0.1), or 48FBA (P = 0.5) between IBS-D and HC groups; however, 20% of IBS-D patients had elevated C4 and 28% had low FGF-19 values.Fecal primary BA was significantly correlated with stool frequency (r = 0.45, P < 0.002). Correlations of C4 with 48FBA and FGF-19 are confirmed in a pediatric population. Twenty percent of pediatric patients with IBS-D had abnormal fasting serum C4. This serum test could be applied to identify BAD in pediatric IBS-D.

The Correlation between Serum C3 and C4 Complement Levels with Disease Activity Systemic Lupus Eritematosus Patients In Dr. Soetomo Hospital, Surabaya

Introduction: The Systemic lupus erythematosus (SLE) is autoimmune disease that results in inflammation, and tissue damage. SLE often creates difficulties in the diagnosis and assessment of disease activity. Disease activity is important as basis for selecting the appropriate therapy. In addition to clinical SLE, supporting investigations are needed to determine disease activity, one of which is complement examination. Complement plays an important role in autoimmune disease and thought to mediate tissue damage. This study aimed to analyze correlation between serum complement C3 and C4 levels with disease activity of SLE patients in Dr. Soetomo Hospital Surabaya.Methods: This study used an observational analytic method with a cross-sectional design. The sampling technique was consecutive sampling. The samples of this study were SLE patients who were treated in the inpatient room and poly rheumatology in January-December 2018 periods. The data were analyzed statistically using the Pearson test.Results: There were 150 SLE patients, most of whom were women (90.0%) with mean age of 29.01±9.8 years. Most levels of complement were low levels (C3 = 48.0% and C4 = 50.7%). Most disease activities were severe flares (44.7%). Results of the Pearson test complement C3 with disease activity were p =0.001, and level of correlation was r =-0.287. However, results of the Pearson test complement C4 with disease activity were p =0.026, and level of correlation was r =-0.182.Conclusion: There is negative correlation between C3 and C4 complement levels with disease activity of SLE patients in Dr. Soetomo Hospital, Surabaya which is significant, weak and opposite.