Serum C3 Levels Research Articles

LRRK2 is involved in the pathogenesis of system lupus erythematosus through promoting pathogenic antibody production

BackgroundSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the presence of pathogenic autoantibodies associated with polyclonal B cell hyperreactivity. Previous study reported that autophagy-related gene Leucine-rich repeat kinase 2 (LRRK2) was likely a susceptible gene for SLE. However, the pathogenic function of LRRK2 in SLE is undefined.MethodsUsing quantitative PCR, we compared the expression levels of LRRK2 in B cells between SLE patients and healthy controls. The expression levels of LRRK2 in in vitro induced CD19hi B cells and naïve B cells were compared as well based on RNA-seq assay. A pristane-induced lupus-like mouse model was used to explore the effects of LRRK2 on the development of SLE. IgG level, B cell subsets in the spleens and bone marrows and pathological features in the kidneys were compared between wildtype (WT) and Lrrk2−/− littermates.ResultsIt was obvious that LRRK2 expression was dramatically up-regulated in primary B cells from SLE patients compared to those from healthy controls, as well as in activated CD19hi B cells. More significantly, LRRK2 expression in B cells was positively correlated with system lupus erythematosus disease activity index (SLEDAI), an indicator for disease severity, and serum IgG levels in SLE patients. Negative correlations were observed between LRRK2 expression and serum C3 or C4 levels, two clinical features associated with SLE-related nephritis. LRRK2 deficiency reduced the death rate of pristane treated mice. Decreased levels of total IgG and autoantibody were detected in the serum with less deposition of immune complexes and attenuated pathological symptoms in the kidneys of Lrrk2−/− mice. Consistent with the reduction in IgG production, the percentages of germinal center B cells and plasma cells decreased significantly as well with LRRK2 deficiency.ConclusionsOur study demonstrates that LRRK2 expression is upregulated in B cells from SLE patients with strong correlations to disease severity. LRRK2 deficiency largely attenuates the pathogenic progress of lupus-like features in pristane-induced mice. This is probably achieved through affecting B cell terminal differentiation and subsequent immunoglobulin production.

Hyperuricemia as an independent predictor and prognostic factor in the development of lupus nephritis

Background: Lupus nephritis (LN) can increase morbidity and mortality risk in systemic lupus erythematosus (SLE) and 25% of the patients with LN will advance to end-stage renal disease. Objective: To evaluate if hyperuricemia is independently associated with the prediction and prognosis of LN. Methods and finding: This cohort study included 80 SLE patients. SLE patients were divided according to uric acid levels in two groups: “Hyperuricemia SLE” group (n=40) and “No Hyperuricemia SLE” group (n=40). Serum uric acid ≥ 6.0 mg/dL in female and ≥ 7.0 mg/dL in male were indicative of hyperuricemia. SLE Disease Activity Index (SLEDAI) scores, serum level of uric acid, renal activity and chronicity index results were collected and recorded. Median value of serum uric acid level for patients with hyperuricemia was 8.6 mg/dl (4.3-10.4) and for patients without hyperuricemia was 4.2 mg/dl (3.3-5.3). LN was observed in 62.5% of group I (SLE with hyperuricemia) in comparison to 20% of group II (SLE without hyperuricemia)” with p<0.001. A statistically significant relation between hyperuricemia and the occurrence of LN was detected. There was also an inverse correlation between serum level of uric acid and both serum C3 level and estimated glomerular filtration rate (p<0.001); however, there was positive correlation of serum level of uric acid with SLE activity and proteinuria, with statistical significance (p<0.001). Renal activity index in hyperuricemic patients (median=7) was higher than that in patients without hyperuricemia. Conclusion: There is a link to be considered between hyperuricemia and the development of new renal damage in SLE affecting both LN activity and severity.

Decreased serum levels of immunoglobulin M and increased complement 3 in Egyptian vitiligo patients

Background Vitiligo is a common, acquired, depigmenting disorder that results from loss of functional melanocytes in the skin and mucous membranes. It is occasionally associated with autoantibodies against the melanocyte-specific proteins such as tyrosine-related protein-1 tyrosine-related protein-2. These antibodies could induce melanocyte damage in vitro by a complement-mediated mechanism and antibody-dependent cellular cytotoxicity might play an active role in the stimulation and inappropriate expression of HLA-DR and induction of intercellular adhesion molecule-1 on melanocytes. Objective Our aim was to assess the serum levels of different immunoglobulins (Ig) in addition to C3 and C4 in vitiligo patients and to determine their correlation with different clinical aspects of the disease. Patients and methods Serum levels of IgG, IgA, and IgM as well as C3 and C4 were estimated in 24 vitiligo patients and 24 healthy controls using the Radial Immuno-Diffusion (immunoprecipitation) technique. Results Serum IgM levels were found to be significantly decreased and C3 levels were significantly increased among patients compared with the controls. No significant difference was found in the serum levels of IgA, IgG, or C4 between both groups. Also, a significant positive correlation was found between serum IgA levels and the age of the patients, as well as between C3 and C4 and a family history of vitiligo. Conclusion Changes in Ig serum levels might be a cause or an effect in the pathogenesis of vitiligo, as well as alterations in the complement system. These ffindings suggest that altered immunity is to be considered in the therapeutic management of these patients.

Interrelationship between Porphyromonas gingivalis and complement C3 and factor B Levels in chronic periodontitis individuals

Background: To evaluate the effect of nonsurgical periodontal therapy on gingival crevicular fluid (GCF) and serum levels of complement C3 and factor B and their correlation with Porphyromonas gingivalis levels in chronic periodontitis (CP) individuals. Materials and Methods: Thirty individuals were divided into three groups. Clinical parameters such as Plaque Index (PI), Gingival Index (GI), Probing depth (PD) and Clinical attachment level (CAL) were recorded and P. gingivalis levels were measured at baseline in Group I (periodontally healthy) and II( chronic periodontits) and 3 months post scaling and root planning (SRP) in Group III subjects. Serum and GCF samples were collected from all the individuals at baseline 3-month post-SRP to evaluate complement C3 and complement factor B levels by spectrophotometer and enzyme-linked immunosorbent assay, respectively. Levels of P. gingivalis were determined by anaerobic culture. Results: Complement C3 and factor B levels in serum and GCF along with P. gingivalis levels in plaque samples showed statistical significance between the groups (P < 0.001). SRP resulted in decrease in C3, factor B, and P. gingivalis levels after 3 months in CP group at P < 0001. Among the periodontal parameters, PD showed significant correlation with biochemical and microbiological parameters in both the groups before and after periodontal therapy. Conclusion: P. gingivalis correlated strongly with factor B values in CP and SRP resulted in reduction of these values suggesting a possible modulation of alternate complement pathway by P. gingivalis.

Clinical application evaluation of serum C1q and other complement factors in the diagnosis and prediction of preeclampsia

Objective To observe the levels of serum complement C1q, C3, C4 and factor B in different phases during normal pregnancy; To evaluate the diagnostic value and the predictive value of serum complement C1q, C3, C4 and factor B in preeclampsia (PE). Methods Three groups of subjectes were enrolled from January 2017 to March 2018 in Department of Obstetrics and Gynecology, Peking University Third Hospital. (1) 30 pregnant women in each group at 8-14 weeks, 20-26 weeks and 28-36 weeks were retrospectively selected, and the serum levels of complement C1q, C3, C4 and B factors were measured and compared. (2)Selecting 17 cases of early-onset mild PE, 47 cases of early-onset severe PE, 24 cases of late-onset mild PE, 27 cases of late-onset severe PE, and 30 normal pregnant cases of the same gestational stage as early-onset / late-onset controls, through ANOVA analysis and comparison between two groups, this study evaluated the diagnostic value of serum complement C1q, C3, C4 and factor B in PE. (3)To evaluate the predictive effect in PE, it analyzed serum C1q and factor B levels of pregnant women at 20-26 gestation weeks through prospective nested case-control study of 214 cases. Results The levels of serum C1q remained stable in the whole pregnancy. The levels of C3 and factor B increased at the early stage of pregnancy and remained stable after the middle stage. C4 increased early in pregnancy and then remained stable. Compared with the control group, the levels of serum C1q in all four types of PE patients were significantly decreased (median: 169 mg/L, 161 mg/L, 165 mg/L, 163 mg/L; early-onset, late-onset control group: 187 mg/L, 194 mg/L; U=130.500, 426.500, 159.500, 130.500, all P 0.05). 33 (15.4%) cases developed PE out of 214 pregnant women with PE risk factors. Compared to those who didn′t develop PE, it showed no statistical difference of serum C1q, C3, C4, and factor B levels at 20-26 gestational weeks of the women who subsequently developed PE (C1q: 175 mg/L vs. 184 mg/L; C3: 1 523 mg/L vs. 1 467 mg/L; C4: 230 mg/L vs. 229 mg/L; FB: 344 mg/L vs. 320 mg/L; U=2 090.000, 1 575.000, 2 058.500, 1 362.000, all P>0.05). Compared to those of the healthy pregnant controls, it showed no statistical difference of serum C1q, C3 and C4 levels of 20-26 gestational weeks of the women who subsequently developed PE (C1q: 175 mg/L vs. 190 mg/L; C3: 1 523 mg/L vs. 1 428 mg/L; C4: 230 mg/L vs. 227 mg/L; U=353.000, 395.000, 493.500, all P>0.05), while it showed statistical difference (344 mg/L vs. 306 mg/L; U= 233.500, P=0.007) for factor B. Conclusions Serum C1q level of PE patients significantly decreased, which can be used as potential indicators of PE diagnosis, but serum C1q, C3, C4 level of 20-26 gestational weeks cannot predict risk of PE. Factor B cannot serve as serum index of PE diagnosis, but its serum levels at 20-26 gestational weeks werer higher than those of normal pregnant controls, factor B may be a potential predictor, but need further verification. (Chin J Lab Med, 2018, 41: 934-942) Key words: Preeclampsia; Complement; C1q; C3; C4; factor B

Early onset of graft glomerulopathy in a patient with post-transplant diabetes mellitus after renal transplantation: a case report

BackgroundPost-transplant diabetes mellitus (PTDM) is an emerging problem in kidney transplantation, representing an important risk factor for kidney function loss. Diabetic nephropathy (DN) occurrence in transplanted kidneys is poorly investigated. Current knowledge describes DN recurrence in graft 5.9 years from kidney transplantation however there is little data about PTDM and DN.Here, we report a clinical case peculiar for an early appearance of advanced glomerular diabetic lesions, after kidney transplantation.Case presentationA 45-year-old Caucasian male affected by autosomal polycystic kidney disease was transplanted with a cadaveric-kidney-donor from 58-year-old male. Induction immunosuppressive therapy included basiliximab and steroids while the maintenance treatment included, tacrolimus, mofetil micophenolate and methylprednisolone.One month after transplantation the patient developed diabetes requiring treatment with repaglinide quickly replaced with insulin to obtain an acceptable glycemic control (HbA1c 52 mmol/mol). Glycosuria was detected persistently during the first six months after transplantation. To achieve further improvement in glycemic control, a shift from tacrolimus to cyclosporine (CyA) was made and steroids were rapidly tapered and stopped. To minimize calcineurin inhibitors toxicity, which was revealed in the 1-year-protocol-biopsy, everolimus was introduced thereby lowering CyA through levels. Moderate hypertension was well controlled with doxazosin. Thirty months after transplantation a second graft biopsy was performed owing to renal function decline and microalbuminuria appearance. Histological analysis surprisingly showed mesangiolysis and microaneurysms; glomerular sclero-hyalinosis and basal membrane thickness and typical nodular glomerulosclerosis. C4d staining was negative and no evidence of immune deposits were detected. Donor Specific Antibodies, serum C3 and C4 levels and autoimmunity tests were negative. Retrospective analysis on donor history didn’t show diabetes or insulin resistance and no diabetic lesions were found in kidney pre-implant biopsy.ConclusionsIn our knowledge, this is the first report describing a very early onset of advanced diabetic glomerular lesions in a graft biopsy after PTDM. We hypothesize that additional factors such as everolimus and hypertension, may have contribute to kidney damage.

Regulatory T Cells and Their Association with Serum Markers and Symptoms in Systemic Lupus Erythematosus and Rheumatoid Arthritis

ABSTRACTPurpose: Impairment in number and functions of regulatory T cells (Treg) has been found to be associated with many autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This study was conducted to identify and compare Treg by flow cytometry using two different staining approaches.Methods: Treg were identified by using CD4+CD25+high and CD4+CD25+CD127dim staining approaches in SLE and RA patients and healthy controls. Association of both identified Treg levels with various serum markers and clinical presentation was also examined.Results: Blood CD4+CD25+CD127dim cells levels were 11.4+3.57 %, 9.76+2.37 % and 6.95+1.16 %; while CD4+CD25+high cells were 1.46+1.09 %, 0.95+0.59 % and 1.87+1.14 % in SLE patients, RA patients and healthy controls respectively. Number of CD4+CD25+CD127dim cells was higher than CD4+CD25+high cells in blood samples of all three study groups. Levels of CD4+CD25+CD127dim cells were significantly higher in SLE and RA patients, compared to healthy controls, but this difference was not observed for CD4+CD25+high Treg. CD4+CD25+high levels showed significant correlation with serum C4, IFN-γ and IL-10 levels in healthy subjects and with C4 levels and fever in SLE patients. CD4+CD25+CD127dim levels showed significant association with alopecia and oral ulcers in SLE patients only, but no correlation with measured serum markers.Conclusion: Results suggest that both staining approaches detect Treg differently and also that Treg play different role in pathogenesis of SLE and RA.

Progressive reduction of serum complement levels: a risk factor for relapse in patients with hypocomplementemia in systemic lupus erythematosus.

Serologically active clinically quiescent (SACQ)-SLE is a subtype of systemic lupus erythematosus (SLE); most SACQ-SLE patients relapse. Although complement and/or anti-dsDNA level fluctuations during SACQ status are reportedly not useful for predicting relapse, they might be useful in specific clinical settings. We aimed to assess the correlation between future relapse and progressive reductions in serum complement levels following remission in patients with hypocomplementemia . We retrospectively reviewed patients aged ≥15 years who were treated with ≥20 mg/day of prednisolone for remission induction. After achieving remission, the patients treated with prednisolone tapered to ≤15 mg/day without relapse and followed by hypocomplementemia (first hypocomplementemia point) were analyzed. The primary outcome was the relapse during the first 24 months. Seventy-six patients were enrolled; 31 (40.8%) relapsed. A ≥10% reduction after the first hypocomplementemia point in serum C3, C4, and CH50 levels was found in 10, 21, and 16 patients, respectively. Hazard ratios (95% confidence intervals) for relapse were 2.32 (0.92-5.12) for serum C3 levels and 2.46 (1.18-5.01) for serum C4 levels. Progressive reductions in serum C3 and C4 levels had relatively high specificity (93.3% and 82.2%) but limited sensitivity (22.6% and 41.9%) for predicting relapse. However, simultaneous progressive reduction in C3 levels and increase in anti-dsDNA antibody levels had the highest specificity (97.8%), and simultaneous progressive reduction in C4 levels or increase in anti-dsDNA antibody levels had the highest sensitivity (71.0%). Simultaneous progressive reductions in complement levels and increases in anti-dsDNA antibody levels may indicate future relapse SACQ-SLE patients.

Characteristic anti-inflammatory and antioxidative effects of enzymatic- and acidic- hydrolysed mycelium polysaccharides by Oudemansiella radicata on LPS-induced lung injury

The present work investigated the antioxidative, anti-inflammatory and pulmonary protective effects of enzymatic- and acid- hydrolysed mycelia polysaccharides (En-MPS and Ac-MPS) from Oudemansiella radicata on LPS-induced acute lung injury (ALI) mice. The results demonstrated that both En-MPS and Ac-MPS showed potential pulmonary protective effects by decreasing serum levels of hs-CRP and C3, increasing pulmonary enzyme values of SOD, GSH-Px, CAT and the level of T-AOC; reducing the activity of MPO; and down-regulating the contents of MDA and LPO. In addition, the levels of TNF-ɑ, IL-1β, and IL-6 in BALF of mice treated with En-MPS at a dosage of 400 mg/kg/d were significantly lower than those in the ALI mice. The in vitro antioxidant effects also showed that the En-MPS was more effective than Ac-MPS. Furthermore, the physical properties of polysaccharides were also investigated by GC, HPGPC, FT-IR and NMR. These results indicated that both En-MPS and Ac-MPS possessed potent antioxidant and anti-inflammatory activities, which could be used as an ingestible drug in preventing lung injury.

Influencing factors of serum complement C3、C4 in children with myasthenia gravis

Objective Complement plays an important role in the pathogenesis of myasthenia gravis.The formation of membrane attck complex and the damage of neuromuscular junction are inseparable from the activation of complement.Then to investigate the influencing factors of serum complement C3, C4 in children with myasthenia gravis and investigate the degree of influence of related factors. Methods One hundred sixty seven cases of hospitalized or outpatient myasthenia gravis children from the Department of Neurology in Hunan Children′s Hospital were collected, including 33 cases of general MG, 134 cases of ocular MG, and 36 cases of normal children as control group.The concentrations of serum C3, C4, IgG, IgM, IgA, IgE were detected by immune compare turbid.The influencing factors of complement C3, C4 were investigated and compared. Results The serum C3 levels were 1.07±0.22 g/L, and the serum C4 levels were(0.17±0.05)g/L in the general MG.The serum C3 levels were(1.01±0.20)g/L, the serum C4 levels were(0.20±0.08)g/L in the ocular MG.There were(1.36±0.28)g/L for C3 levels, (0.25±0.11)g/L for C4 levels in the control group.Compared with the control group, there were significant difference in C3 and C4 between the general MG and ocular MG(P<0.01 or 0.05). The partial correlations coefficients of C3 and course of disease, IgG and C3, C3 and C4 were-0.162, 0.135, 0.446(P<0.01 or 0.05). The multiple linear regression equations were as followed: C4=0.420×C3, C3=0.655+ 1.148×C4+ 0.008×body weight -0.005×course of disease.Using univaruate analysis, the effect factors of C4(F=18.151, P=0.000), body weight(F=6.420, P=0.003), course of disease(F=3.015, P=0.039), age× course of disease×body weight(F=2.997, P=0.042)to C3 were significant(P<0.05, or P<0.01). Conclusion The C3 levels are mainly affected by C4, body weight, duration and some interaction effects among several impact factors in children with MG.C4 is mainly affected by C3. Key words: Children; Myasthenia gravis; Humoral immunity; Complement 3; Complement 4

SLE and Serum Complement: Causative, Concomitant or Coincidental?

Background Systemic Lupus Erythematosus (SLE) is an incurable autoimmune disorder with complement activation playing a key role in the pathogenesis of immune-mediated tissue injury. While quantifying complement to monitor SLE disease activity has been the standard of care since the 1950s, decreased complement levels are not consistently associated with flares. Objective We seek to clarify the SLE phenotype in which complement deficiency is causative, concomitant, or coincidental. Methods A PUBMED literature review was conducted using key words 'complement,' 'SLE,' and 'SLE flares' in English-only journals from 1972-2017. Relevant clinical studies and review articles were found that examined the measurement of complement levels in SLE, and more specifically, interpretation of low serum complement levels regardless of disease activity. Conclusion Complement activation plays a key role in the pathophysiology of SLE and it is recommended to continue monitoring serum levels of C3 and C4 to assess for disease activity. However, it is important to note that decreased serum complement is not consistently associated with disease flares.It is clinically important to find novel ways to assess disease activity in SLE. Reduced serum levels of cell-bound complement activation products may more accurately reflect disease activity than conventional serum C3 and C4 monitoring.

Decreased Serum Levels of Complement C3 Reflect Complement System Dysregulation in Patients With Primary Open-angle Glaucoma: Results From a Pilot Study.

To evaluate the serum complement component (C)3 concentration in patients with primary open-angle glaucoma (POAG) and to investigate the association between C3 levels and POAG severity. This study enrolled 190 consecutive POAG patients and 204 normal control subjects. A detailed eye and systematic examination, including intraocular pressure, gonioscopy, fundus photography, A-scan ultrasound, visual field testing, electrocardiograms, x-rays, liver function, renal function, infectious disease, etc., and measurement of serum C3 concentration by immunoturbidimetry, was performed. The subgroups were classified according to age (17 to 29, 30 to 49, 50 to 69, 70+ y), sex, and visual field: mild (MD≤6 dB), moderate (6 dB<MD≤12 dB), and severe (MD>12 dB) glaucoma. The serum C3 level of the POAG (95.63±17.71 mg/dL) was ∼20.93% lower than that of the control group (115.65±22.19 mg/dL) (P<0.001). A similar result was observed when serum levels of C3 were compared between the POAG and control groups with respect to age and sex. The mean serum C3 level was lowest in the severe POAG group (85.18±19.62 mg/dL), followed by the moderate POAG group (96.62±12.63 mg/dL) and the mild POAG group (110.44±14.89 mg/dL) (P<0.001). Multiple logistic regression analyses revealed a significant correlation between the C3 levels and the vertical cup-disc ratio (B=-0.373, P=0.026), C3 levels and MD (B=-0.546, P=0.001). Logistic regression analyses revealed that serum C3 levels were associated (odds ratio=0.939, 95% CI=0.901-0.979, P=0.003) with severity of POAG. The POAG patients had decreased C3 levels, which were further negatively associated with POAG severity, suggesting the involvement of C3 in the pathomechanisms of POAG.

Low serum complement 3 level is associated with severe ANCA-associated vasculitis at diagnosis.

We investigated whether low serum C3 level can cross-sectionally estimate severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in immunosuppressive drug-naïve patients at diagnosis. We retrospectively reviewed the medical records of 139 patients with AAV, who were first classified as AAV at Severance Hospital. We obtained clinical and laboratory data including serum complement 3 (C3) level and calculated Birmingham vasculitis activity score (BVAS) at diagnosis. We stratified AAV patients into three groups according to the tertile of BVAS and defined the lower limit of the highest tertile as the cutoff for severe AAV (BVAS at diagnosis ≥ 16) at diagnosis. Low serum C3 level was defined as C3 < 90mg/dL. The odds ratio (OR) was assessed using the multivariable logistic regression. The mean age at diagnosis was 56.3years and 41 patients were men (29.5%). The mean initial BVAS was 12.8. The mean serum C3 and C4 levels were 110.6 and 26.8mg/dL. Thirty-one patients (22.3%) exhibited low serum C3 level at diagnosis. In the multivariable analysis, serum C3 level at diagnosis < 90mg/dL (OR 2.963) exhibited the significant association with severe AAV at diagnosis. Patients with low serum C3 level exhibited a significantly high relative risk (RR) for severe AAV at diagnosis compared to those without (RR 3.600). Patients with low serum C3 level at diagnosis exhibited poor renal prognosis than those without. Low serum C3 level can estimate severe AAV and predict poor renal outcome in immunosuppressive drug-naïve patients at diagnosis.

Increased Serum C3 and Decreased UA in Patients of Bipolar Disorder in Chinese Han Population.

The aim of this study is to explore the changes and clinical significance of serum C3, C4, hypersensitive C-reactive protein (hsCRP) and uric acid (UA) in patients of bipolar disorder (BD). In this case-control study, we recruited 141 BD patients from The Second Xiangya Hospital, Central South University, and 151 age and gender matched healthy controls (HC) from the health management central of The Second Xiangya Hospital. These patients were divided into two subgroups based on medicines use: 91 patients were treated with psychiatric drugs and 50 patients were drugs free, or four subgroups based on mood states: 54 patients in manic/hypomanic phase, 30 patients in depressive phase, 52 patients in euthymic phase and 5 patients in mixed phase. Serum levels of C3, C4, hsCRP and UA were measured in all subjects. The serum C3 levels in BD patients (0.9981 ± 0.1849 g/L) were significantly lower than that in HC group (1.0637 ± 0.2186 g/L), especially the drugs free subgroup and the euthymic subgroup (0.975 ± 0.153 and 0.983 ± 0.182 g/L), while the serum UA levels were significantly higher (354.6 ± 90.4 vs. 332.9 ± 88.7 μmol/L), especially the drug-treated subgroup and manic/hypomanic subgroup (361.56 ± 93.20 and 376.70 ± 88.89 μmol/L), and rates of hyperuricaemia (31.91 vs. 17.88%) were significantly higher in BD patients than in HC group. The serum C4 and hsCRP levels in HC group showed no significant difference with BD patients in whole or those subgroups. These findings suggested that the complement and purinergic systems of BD patients might be disrupted, the UA levels could be a potential marker in manic phase and the C3 might be the marker of therapeutic evaluation of BD patients.

Adipokine interactions promote the pathogenesis of systemic lupus erythematosus

BackgroundAdipokines are chemical mediators released from adipose tissue involved in regulation of appetite, insulin sensitivity, immune system and inflammatory responses. Adipokines contributes to low grade inflammatory response in autoimmune disease like Systemic Lupus Erythematosus (SLE) but the pathophysiology is yet not clear. The aim of this study is to understand role of adipokine interactions in SLE disease pathogenesis. MethodsSixty newly diagnosed treatment naïve SLE patients fulfilling the ACR criteria and forty age-sex matched healthy subjects were enrolled in thiscase-control study. Disease activity in SLE patients was evaluated using SELENA-SLEDAI.Array of adipokines, C1q circulating immune complexes (C1q-CIC), anti-C1q, anti-ribososmal P0 (anti-RibP0) and anti-mitochondrial antibodies (AMA) levels were detected by ELISA. Antinuclear antibodies (ANA) and anti-dsDNA autoantibodieswere detected by Indirect Immunofluorescence (IIF), while antigen specificities were detected by Immunoassay blot. Serum levels of C3 and C4 complement factors were assessed by nephlometer. ResultsStatistically significant elevation in progranulin, adipsin and resistin levels was seen among SLE patients when compared to healthy controls (p < 0.0001). Leptin and omentin levels were significantly reduced in SLE patients (p < 0.0001). There was no statistically significant difference in serum adiponectin, chemerin and visfatin levels when these two groups were compared (p > 0.05). Adiponectin, adipsin and resistin levels were elevated in SLE patients with renal manifestations (p < 0.05). Reduced leptin levels were significantly associated with presence of renal manifestations (p < 0.05). Adiponectin levels positively correlated with disease activity (r = 0.294, p = 0.027) whereas negatively correlated with C3 levels (r = −0.439, p = 0.0007). A positive correlation was observed between hypocomplementemia and leptin levels (p < 0.05). Leptin levels were negatively correlated with disease activity, anti-dsDNA, C1q-CIC and anti-C1q levels (p < 0.05). A significant positive correlation was observed between progranulin levels and anti-ribosomal P0 antibodies (r = 0.499, p < 0.0001). ConclusionAdipokines levels and associated clinical manifestations suggest involvement of adipokines in disease pathogenesis of SLE. SLE disease activity and complement components may suggest regulatory effect of adipokines (adiponectin and leptin) on disease pathogenesis. Further studies on adipokines in SLE patients with renal manifestations may propose them as prognostic markers in renal damage.Trial Registration: NA

Innate Immune System Status of Sulphur Mustard-Poisoned Iranian Veterans Three Decades after Exposure.

Sulphur mustard (SM) is an incapacitating chemical warfare agent which causes acute and chronic toxicities in different body organs of affected individuals. The aim of this study was to investigate the innate immune status of the Iranian veterans who were exposed to SM around 30 years earlier and had more than 25% disabilities. In this regard, most functional and non-functional parameters of innate immunity were evaluated in 35 veterans. Phagocytic activity, nitroblue tetrazolium (NBT) reduction assay and haemolytic complement activity (HCA) in addition to routine haematological parameters, serum protein electrophoresis, complements C3 and C4 levels were studied. Measures of haematological parameters, serum proteins, C3 and C4 were almost within the normal range. Functional experiments such as phagocytic activity, NBT reduction assay and HCA were normal as well. However, serum protein analysis revealed a fair decrease in percentages of α1 -globulin. Mean values of the parameters of innate immune system of the veterans three decades after SM poisoning were almost within the upper and lower normal limits. Reduced α1 -globulin - maybe subsequent to a chain of SM-induced genetic disorders - may have been the result of α1 -antitrypsin deficiency which may result in prevalent respiratory complications among these veterans. As a supplementary study, measurement of serum α1 -antitrypsin in SM-poisoned veterans could be beneficial. Further studies are required to prove this hypothesis. Further investigations on the evaluation of the acquired immunity parameters as the second line of defence may reveal a better understanding of SM veterans' immune system status.

Complement protein and Immunoglobulins Serum levels in Normal Pregnant and Spontaneous Aborted Women

Disorder of maternal immune responses during pregnancy triggers immunological rejection of fetus antigens by maternal immune components, contribute to spontaneous abortion or miscarriage. The study was designed to concentrated on immunoglobulins (IgM, IgG and IgA) and complement elements (C3 and C4) serum levels changes in normal pregnant and abortion women. Study groups were classified into normal pregnant women (20), spontaneous abortion (30) and non-pregnant women (16) as a control group, attending to Shahid Dr. Khalid Hospital/Department of Gynecology and Obstetrics/Koya city. Serum levels of immunoglobulins (IgG, IgM, and IgA), complement proteins (C3 and C4) were determined and analyzed for normal pregnant, abortion and control groups by using Single Radial Immunodiffusion (SRID) technique. The results demonstrated that concentration of IgG levels in abortion differed significantly in compare to normal pregnancy (p ≤0.05), while there were no significant differences in IgM and IgA serum levels among groups (p &gt;0.05). Also, statistical analysis revealed that serum levels of C3 and C4 significantly decreased in abortion group compared to normal pregnant and non-pregnant groups (p ≤0.05). Concluded that complement proteins (C3 andC4) are a good defense line during normal pregnancy, sometime activation (hyper-consuming) of complement elements may provoke spontaneous abortion, while immunoglobulins are a little role in inducing of miscarriage in pregnant women.

Role of complement system in patients with biopsy-proven immunoglobulin G4–related kidney disease

Hypocomplementemia has been frequently reported in immunoglobulin G4-related kidney disease (IgG4-RKD). However, studies on the role of complement system in IgG4-RKD are lacking. A total of 40 429 renal biopsies from January 2010 to January 2018 were reexamined in the present study, and 17 patients were confirmed to meet the criteria of IgG4-RKD. According to the serum C3 levels, they were divided into 2 groups: the low-C3 group (C3 <0.8 g/L, n = 7) and the normal-C3 group (C3 ≥0.8 g/L, n = 10). Compared with the normal-C3-level group, the patients in the low-C3-level group had lower serum C4 concentrations (P = .025), higher serum IgG4 concentrations (P = .003), higher positive rates in rheumatoid factor (P = .033), more severe storiform fibrosis (P = .007) at diagnosis, and higher blood urea nitrogen levels at the latest test (P = .04). The serum levels of C3 were in negative correlation with the serum levels of IgG4 (P = .003), the levels of rheumatoid factor (P = .002), renal deposition of C1q (P = .028), storiform fibrosis (P < .001), scores of interstitial fibrosis (P = .015), the amount of renal IgG4-positive (IgG4+) plasma cells (P = .020), the ratios of IgG4+ plasma cells/CD138+ cells (P = .018), and the blood urea nitrogen concentrations at the last test (P = .023). Our study shows that IgG4-RKD is a relatively rare entity. Complement system may participate in the development of IgG4-RKD.

Serum-soluble CXCL16 in juvenile systemic lupus erythematosus: a promising predictor of disease severity and lupus nephritis.

Juvenile systemic lupus erythematosus (jSLE) is a multisystem autoimmune disease of unpredicted course and prognosis. Rates of organ involvement in SLE are higher in children, and overt lupus nephropathy is more often a presenting manifestation of SLE in children than adults. Inflammatory soluble chemokine CXC motif-ligand 16 (sCXCL16) is an important pathogenic mediator in inflammatory diseases as SLE. Herein, we aimed to evaluate serum level of sCXCL16 in jSLE patients in comparison to healthy controls and to correlate it with disease activity and extent of cutaneous and renal affection, to detect its possible role in disease pathogenesis. Serum level of sCXCL16 was determined by ELISA in 27 patients with jSLE (mean age 12.35years ± 2.26 SD) in addition to 30 age- and sex-matched healthy controls and correlated with clinical and laboratory parameters in lupus group. Serum sCXCL16 was significantly higher in jSLE patients than controls (P≤ 0.001), and it correlated positively with SLE disease activity, severity of lupus nephritis, 24-h urinary protein, anti-dsDNA titre, blood pressure, and ESR, while it correlated negatively with serum C3 levels. Serum sCXCL16 was higher in jSLE patients with alopecia and malar erythema. Serum sCXCL16 might play a role in inflammatory pathogenesis of jSLE particularly in periods of disease activity. It might serve as a future useful laboratory test for detection of jSLE activity, renal insult, and its severity which might limit the need for invasive renal biopsies in such a delicate patient population.

Clinical characteristics and risk factors of infections in patients with systemic lupus erythematosus.

To investigate the clinical characteristics of infection in SLE patients and analyze the risk factors of infection. A retrospective analysis method was used and the data were collected from 173 case times of 142 hospitalized patients. We found the incidence rate of infections in SLE was 50.7%. The most common infection sites were lungs, followed by upper respiratory tracts and urinary tracts. The most common pathogens were bacteria, followed by fungi. The infection-associated risk factors were duration of hospitalization, lupus activity state, the use of high-dose corticosteroids and immunosuppressive agents, the low serum level of complements 3 and 4 (C3 and C4), fever, the high level of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), the abnormality of white blood cell (< 4 × 109/L or > 10 × 109/L), and the low level of albumin (P < 0.05 or P < 0.001). The independent risk factors for SLE patients with infection consist of the abnormality of white blood cells, the high level of CRP, the low serum level of C4, and longtime hospitalization. Attention should be paid to the risk factors of infection, and treatment to enhance immunity should be carried out to reduce the chance of infection.