Albumin to globulin ratio (AGR) in systemic lupus erythematosus: correlation with disease activity.

OBJECTIVE: To investigate the role of albumin-to-globulin ratio (AGR) in systemic lupus erythematosus (SLE) and its relationship with disease activity. METHODS: This retrospective study consecutively selected patients with SLE and healthy controls. Patients were divided into three groups according to the SLE Disease Activity Index 2000 (SLEDAI-2K): group 1 (mild disease activity, SLEDAI-2K ≤ 6), group 2 (moderate disease activity, SLEDAI-2K 7-12) and group 3 (severe disease activity, SLEDAI-2K > 12). Predictors of SLE disease activity were analysed by ordinal logistical regression. RESULTS: A total of 101 Chinese patients with SLE and 75 healthy Chinese controls were included. Patients with SLE had lower AGR values than healthy individuals, and group 3 patients with SLE displayed lower AGR values than those in group 1, but similar values to group 2. AGR was inversely correlated with SLEDAI-2K (r = -0.543). Ordinal logistic regression analysis showed that lower AGR (ß = -1.319) and lower complement C4 (ß = -1.073) were independent risk factors for SLE disease activity. CONCLUSIONS: AGR was decreased in patients with SLE and may be utilized as a useful inflammatory biomarker for monitoring SLE disease activity.

Serum concentrations of complement C3 and C4 in dogs with idiopathic epilepsy.

BACKGROUND: High concentrations of complement factors are presented in serum of animal epilepsy models and human patients with epilepsy. OBJECTIVES: To determine whether complement dysregulation occurs in dogs with idiopathic epilepsy (IE). ANIMALS: The study included 49 dogs with IE subgrouped into treatment (n = 19), and nontreatment (n = 30), and 29 healthy dogs. METHODS: In this case-control study, the serum concentrations of the third (C3) and fourth (C4) components of the complement system were measured using a canine-specific ELISA kit. RESULTS: Serum C3 and C4 concentrations were significantly higher in dogs with IE (C3, median; 4.901 [IQR; 3.915-6.673] mg/mL, P < .001; C4, 0.327 [0.134-0.557] mg/mL, P = .03) than in healthy control dogs (C3, 3.550 [3.075-4.191] mg/mL; C4, 0.267 [0.131-0.427] mg/mL). No significant differences were observed in serum C3 and C4 concentrations between dogs in the treatment (C3, median; 4.894 [IQR; 4.192-5.715] mg/mL; C4, 0.427 [0.143-0.586] mg/mL) and nontreatment groups (C3, 5.051 [3.702-7.132] mg/mL; C4, 0.258 [0.130-0.489] mg/mL). Dogs with a seizure frequency >3 times/month had significantly higher serum C3 (6.461 [4.695-8.735] mg/mL; P < .01) and C4 (0.451 [0.163-0.675] mg/mL; P = .01) concentrations than those with a seizure frequency ≤3 times/month (C3, 3.859 [3.464-5.142] mg/mL; C4, 0.161 [0.100-0.325] mg/mL). CONCLUSIONS AND CLINICAL IMPORTANCE: Dysregulation of classical complement pathway was identified in IE dogs. Serum C3 and C4 concentrations could be diagnostic biomarkers for IE in dogs with higher seizure frequency.

IMMUNOLOGICAL DISORDERS AND COLON DYSBIOSIS IN OBESE PATIENTS WITH HYPOTHYROIDISM.

OBJECTIVE: The aim: To investigate the peculiarities of immunological changes and their relationship with colon dysbiosis in obese patients with HT. PATIENTS AND METHODS: Materials and methods: The examined patients included 48 patients with HT and obesity (group 1) and 34 patients with obesity (group 2). Patients under¬went fecal analysis for dysbiosis. The levels of complement, namely C3 and C4 and the concentration of immunoglobulins (IgA, Ig M, IgG) were determined by means of chromogenic analysis. RESULTS: Results: During the clinical examination, constipation and flatulence were more often diagnosed in patients of group I (58.3% and 66.7%, respectively - p<0.001), while in patients of group 2 with increased BMI without thyroid dysfunction, a tendency to diarrhea was more often found, accompanied by periodic pain along the colon (50.0% and 32.3% of patients, respectively - p<0.001). Changes in the immunological status of patients in both groups were found. In patients with HT and increase of BMI an increase in serum IgA, IgM, IgG levels were found. An increase in serum immunoglobulins (A, M and G) was also diagnosed in group 2 of examined patients too. CONCLUSION: Conclusions: 1. In patients with obesity decrease in the concentration of Bifidobacterium, Lactobacillus and increase in the number of Staphylococcus, Clostridium, Proteus and Klebsiella were detected, which is more pronounced in patients with a combination of obesity and hypothyroidism. 2. Impairment distinct of immu¬nological status in patients with hypothyroidism and obesity was diagnosed, which was manifested by increased levels of immunoglobulins, namly (A, M, G), as well as a decrease in blood serum complements (C3, C4). 3. The level of IgA, G directly depends on the decrese of Bifidobacterium, Lactobacillus and increse of Staphylococcus, Clostridium and Klebsiella in patients with obesity, which is more pronounced in patients with a combination of obesity and hypothyroidism.

Serum miRNA-21, miRNA-146a and plasma cell free DNA as novel biomarkers for assessing systemic lupus erythematosus activity.

BACKGROUND: MicroRNA and cell-free DNA have shown significant correlations with several autoimmune disorders including systemic lupus erythematosus (SLE). SLE has been associated with challenges in determining its activity, so that the need for biomarkers contributing to assessing its activity is emerging. The current study investigated miRNA-21, miRNA-146a and plasma cf-DNA in determination of SLE activity, in addition their association with clinical data including complement factor 3 (C3), complement factor(C4), anti-dsDNA, and other disease activity indices. METHODS AND RESULTS: Eighty subjects divided into; twenty active patients (with SLE-DAI2K score of 16-18) twenty inactive patients (with SLE-DAI2K score of 1-3), and forty healthy control participants) were included in this study. Serum miR-21, miR-146a, and plasma cf-DNA were quantified by real time PCR and their correlation with clinical data was statistically analyzed. The results demonstrated that active cases have significant upregulation of serum miRNA-21 and plasma cf-DNA. Moreover, miR-21 showed a negative, significant pertaining to C3, C4 and was positively related to Systemic Lupus Erythematosus Disease Activity Index 2 K score (SLE-DAI Index2K score) and Systemic-Lupus-Erythematosus-Disease Activity-Index 2 K activity (SLE-DAI 2 K activity). Also, Active group miRNA-146a was negatively, significantly correlated with C3, as well as a positive significant relationship with SLE-DAI2K score and SLEDAI 2 K activity, in addition to anti DNA Autoantibodies. Furthermore, miR-21 and cf-DNA demonstrated a differential value through Receiver Operating Characteristic (ROC) curve's study. CONCLUSIONS: the present study illustrated miR-21, miR-146a, and cf-DNA relationship with SLE clinical data. In addition to their potential value in SLE diagnosis, and activity determination.

A model incorporating serum C3 complement levels may be useful for diagnosing biliary atresia in infants / Un modelo que incorpore niveles séricos de C3 del complemento podría ser de utilidad para el diagnóstico de atresia biliar en niños

Introduction: Correctly identifying patients with biliary atresia (BA), while avoiding invasive diagnostic methods is challenging. The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants.Patients and methods: The data of infants with a surgical/histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed. Patients were divided into a BA group and a cholestasis control (CC) group. Biochemical parameters, major lymphocyte subsets, immunoglobin and C3 and C4 complement levels were compared between the groups.Results: A total of 129 infants with BA and 63 with other causes of cholestasis (CC control group) with a median age of 2.2 months were included in the analysis. The levels of CD3+ T cells, CD3+CD4+ T cells, and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group (all P<0.05). Pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with γ-GT in the BA group, but not in the CC group. Five indices were found to be significantly associated with BA: stool color, globulin, γ-GT, C3 and C4. A model incorporating stool color, gamma-glutamyl transpeptidase level, and C3 level exhibited an area under the ROC curve (AUC) of 0.93, and a sensitivity of 93% and specificity of 83% for the diagnosis of BA.Conclusions: Models incorporating serum C3 levels may be useful for accurately diagnosing BA in infants.

Introducción: Es difícil la identificación correcta de los pacientes con atresia biliar (AB), evitando los métodos diagnósticos invasivos. El objetivo de este estudio fue determinar el valor de los indicadores inmunológicos séricos para distinguir AB de otras causas de colestasis en niños.Pacientes y métodos: Se analizaron retrospectivamente los datos de niños con diagnóstico quirúrgico/histológico de AB y los datos de niños con otras causas de ictericia colestásica. Se dividió a los pacientes entre el grupo AB y el grupo de control de colestasis (CC). Se comparó entre los dos grupo los parámetros bioquímicos, principales subconjuntos linfocíticos, inmunoglobina y niveles séricos de C3 y C4 del complemento.Resultados: Se incluyó en el análisis a un total de 129 niños con AB y 63 con otras causas de colestasis (grupo control CC) con una edad media de 2,2 meses. Los niveles de células T CD3+, células T CD3+CD4+, células T prematuras y los niveles de C3 y C4 fueron significativamente más altos en el grupo AB en comparación con el grupo CC (all P < 0,05). Los análisis de correlación pareada indicaron que C3 y C4 tenían una correlación positiva significativa con -GT en el grupo AB, pero no en el grupo CC. Se determinó que cinco índices estaban significativamente asociados a AB: color de las heces, globulina, -GT, C3 y C4. Un modelo que incorporó el color de las heces, nivel de gamma-glutamil transpeptidasa, y nivel de C3 reflejó un área bajo la curva ROC (AUC) de 0,93, sensibilidad del 93% y especificidad del 83% para el diagnóstico de AB.Conclusiones: Los modelos que incorporan niveles séricos de C3 pueden ser de utilidad para diagnosticar AB de manera precisa en niños.

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.

A model incorporating serum C3 complement levels may be useful for diagnosing biliary atresia in infants.

INTRODUCTION: Correctly identifying patients with biliary atresia (BA), while avoiding invasive diagnostic methods is challenging. The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants. PATIENTS AND METHODS: The data of infants with a surgical/histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed. Patients were divided into a BA group and a cholestasis control (CC) group. Biochemical parameters, major lymphocyte subsets, immunoglobin and C3 and C4 complement levels were compared between the groups. RESULTS: A total of 129 infants with BA and 63 with other causes of cholestasis (CC control group) with a median age of 2.2 months were included in the analysis. The levels of CD3+ T cells, CD3+CD4+ T cells, and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group (all P<0.05). Pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with γ-GT in the BA group, but not in the CC group. Five indices were found to be significantly associated with BA: stool color, globulin, γ-GT, C3 and C4. A model incorporating stool color, gamma-glutamyl transpeptidase level, and C3 level exhibited an area under the ROC curve (AUC) of 0.93, and a sensitivity of 93% and specificity of 83% for the diagnosis of BA. CONCLUSIONS: Models incorporating serum C3 levels may be useful for accurately diagnosing BA in infants.

A 56-Year-Old Man With Emphysema, Rash, and Arthralgia.

CASE PRESENTATION: A 56-year-old man presented to the pulmonary clinic with dyspnea and hypoxemia on exertion. He was an avid biker and skier who had noticed a significant decrease in high-level physical activity over the past 3 years. He reported dyspnea, desaturations at altitudes higher than 9,000 feet, dry cough, tachycardia, and palpitations with exercise. Review of systems was also notable for gluten-intolerance, Raynaud's phenomenon, recurrent skin lesions and joint swelling, pain, and stiffness in the areas overlying the jaw, wrists, knees, and ankles (after capsaicin exposure). He denied fever, chills, anorexia, weight loss, hair loss, ocular symptoms, jaw claudication, chest pain, or lower extremity swelling. He had a five pack-year smoking history, no history of prematurity, childhood asthma, recurrent infections, or environmental and occupational exposure. Based on pulmonary function tests from an outside provider, he had received a diagnosis of exercise-induced asthma and had been prescribed an albuterol inhaler to use on an as-needed basis, which failed to improve his symptoms. He was later prescribed a mometasone-formoterol inhaler, still with no symptomatic improvement.

C3 and C4 complement levels in AQP4-IgG-positive NMOSD and in MOGAD.

While complement-dependent cytotoxicity (CDC) is a known effector mechanism in aquaporin-4-immunoglobulin (Ig)G-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD), the role of CDC in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is less clear. We determined complement C3 and C4 plasma concentrations in patients with clinically stable AQP4-IgG+ NMOSD (n = 16), MOGAD (n = 15), early multiple sclerosis (MS, n = 19) and in healthy controls (HC, n = 18). C4 was lower in AQP4-IgG+ NMOSD than in MOGAD, MS and HC (p < 0.05, pairwise comparisons). C3 was lower in AQP4-IgG+ NMOSD than in MS (p = 0.034). These findings suggest subtle complement consumption in clinically stable AQP4-IgG+ NMOSD, but not in MOGAD.

Complement Detection in Mouse Kidneys by Immunofluorescence.

Immunofluorescence staining of tissues has become a reliable and informative technique used in a diverse set of applications, ranging from simple detection of an antigen of interest in a specific location to the semiquantitative analysis of spatial relationships between multiple antigens and/or cell types. During complement activation, circulating complement proteins are covalently fixed to target tissues, providing a durable marker of complement activation in the tissue, and many of these proteins can be readily detected by immunofluorescence microscopy. In general, staining for complement fragments is much like staining for other noncomplement epitopes. However, one key difference is the diligence with which unfixed tissues must be handled when staining for complement fragment. Here we explain the process of dual staining frozen mouse kidney sections for the complement proteins C3 and C4. Throughout the protocol, we will emphasize important steps for preserving complement protein integrity as well as tips to improve the signal-to-noise ratio to improve overall image quality.

Characteristics of immune function in the acute phase of Henoch-Schönlein purpura.

BACKGROUND: Henoch-Schönlein purpura (HSP) is still diagnosed using symptoms and signs together with some histopathological findings. The purpose of this study was to summarize the characteristics and roles of cellular and humoral immunity in children with Henoch-Schönlein purpura (HSP). METHODS: A total of 502 cases of patients with acute HSP were diagnosed and observed. The levels of T lymphocyte subsets, natural killer cells (NK cells), and B cells were analyzed by flow cytometry. The serum immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), and complement C3 (C3) and complement C4 (C4) levels were detected by velocity scatter turbidimetry. RESULTS: Compared with the healthy groups, the levels of cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4), B cells, and NK cells and ratio of CD4/CD8 in patients with HSP were decreased (P < 0.05). The levels of IgG, IgA, IgM, and C3 were increased (P < 0.05). Compared with the Kawasaki disease (KD) group, the levels of CD3, CD4, CD8, B cells, NK cells, and IgA in patients with HSP were increased (P < 0.05), and the ratio of CD4/CD8 and levels of IgM, C3, and C4 was decreased (P < 0.05). Compared with the pneumonia group, the levels of CD3, CD4, B cells, and IgA in patients with HSP were increased (P < 0.05), and the ratio of CD4/CD8 and levels of IgM and C4 was decreased (P < 0.05). CONCLUSIONS: Cellular immunity and humoral immunity were all involved in the pathogenesis of HSP. The decline of NK cells, B lymphocyte cells, CD3, CD4 the increased secretion of immunoglobulin, and the abnormal appearance of IgA and C3 may exist during the progression. It may indicate a worse prognosis and increasing the risk of dedifferentiation. Cellular immunity was lower, which lead to increased production of inflammatory mediators and increased secretion of immunoglobulin, which then mediated systemic small-vessel vasculitis. Key Points • The pathogenesis of Henoch-Schönlein purpura (HSP) was not completely illuminated. • There was a lack of disease-specific laboratory abnormalities that can be used in the clinical diagnosis of HSP. • We compared the laboratory abnormalities in the immune system of HSP with KD and pneumonia. • Cellular immunity and humoral immunity were all involved in the pathogenesis of HSP. Cellular immunity was lower, which lead to the following pathological changes.

Features of serum complement C3 and C4 levels in autoimmune hemolytic anemia patients.

INTRODUCTION: Abnormally activated complement system induces erythrolysis in a part of autoimmune hemolytic anemia (AIHA) patients. However, the alterations in serum complement levels in these patients are seldom reported. In this study, we aimed to evaluate the serum complement features of AIHA patients according to different clinical and laboratory characteristics and to find relationships between complement levels and hemolysis-associated laboratory indexes. METHODS: A retrospective analysis of 146 AIHA patients was performed, and serum complement C3 and C4 levels were compared between control subjects and AIHA patients with different subtypes. Correlations of serum C3/C4 levels with titers of cold agglutinin test (CAT), direct antiglobulin test (DAT), and serological indexes were assessed. Spearman correlation analysis was performed to analyze the relationship between serum complement levels and other laboratory indexes. RESULTS: Autoimmune hemolytic anemia patients showed reduced serum C3 levels, while serum C4 levels tended to be lower in DAT-positive AIHA patients but not in DAT-negative AIHA patients. Patients with warm AIHA secondary to connective tissue diseases and cold agglutinin disease/cold agglutinin syndrome had the lowest serum C3/C4 levels. Serum C4 levels were negatively correlated with CAT (P = .004) and DAT (anti-C3d) (P = .007) titers. In patients with positive CAT and/or DAT (anti-C3d) but negative DAT (anti-IgG), serum C3/C4 levels were negatively correlated with indirect bilirubin (P = .017 and =.026, respectively). CONCLUSION: The study findings may be helpful in not only unraveling the mechanism underlying hemolysis in AIHA but also diagnosing AIHA and selecting targeted treatment strategies.

Mean platelet volume in children with systemic lupus erythematosus.

BACKGROUND: Platelets are heterogeneous in size, density, metabolic, functional, and biochemical properties. Mean platelet volume (MPV) is a measure of the average size of platelet in a blood sample. AIM: We aimed to evaluate the mean platelet volume as a marker for disease activity in children with systemic lupus erythematosus. MATERIALS AND METHODS: This was a prospective case-control study, which included 50 patients with SLE and 50 age and sex, matched healthy controls. All subjects were subjected to history taking, physical examination and laboratory parameters in active and remission phases of the diseases. RESULTS: The MPV value in the SLE group was significantly higher than control group (9.6 ± 1.3 fL, 9.1 ± 0.57 fL, respectively, p = 0.04). There was a significant increase of weight, blood pressure, urea, creatinine, proteinuria, CRP, ESR, cholestrol, MPV values, SLEDAI-2K scores and significant decrease of HB, albumin, C3, mean platelet volume (MPC) in the active stage than in the remission stage. There was a significant negative correlation between MPV and MPC in active stage of the disease but the correlation was insignificant in remission stage. CONCLUSION: MPV increased in active phase of patients with SLE and can be an easy, rapid, inexpensive and simple method to assess disease activity in children with SLE.

Diagnostic and Prognostic Significance of Complement in Patients With Alcohol-Associated Hepatitis.

BACKGROUND AND AIMS: Given the lack of effective therapies and high mortality in acute alcohol-associated hepatitis (AH), it is important to develop rationally designed biomarkers for effective disease management. Complement, a critical component of the innate immune system, contributes to uncontrolled inflammatory responses leading to liver injury, but is also involved in hepatic regeneration. Here, we investigated whether a panel of complement proteins and activation products would provide useful biomarkers for severity of AH and aid in predicting 90-day mortality. APPROACH AND RESULTS: Plasma samples collected at time of diagnosis from 254 patients with moderate and severe AH recruited from four medical centers and 31 healthy persons were used to quantify complement proteins by enzyme-linked immunosorbent assay and Luminex arrays. Components of the classical and lectin pathways, including complement factors C2, C4b, and C4d, as well as complement factor I (CFI) and C5, were reduced in AH patients compared to healthy persons. In contrast, components of the alternative pathway, including complement factor Ba (CFBa) and factor D (CFD), were increased. Markers of complement activation were also differentially evident, with C5a increased and the soluble terminal complement complex (sC5b9) decreased in AH. Mannose-binding lectin, C4b, CFI, C5, and sC5b9 were negatively correlated with Model for End-Stage Liver Disease score, whereas CFBa and CFD were positively associated with disease severity. Lower CFI and sC5b9 were associated with increased 90-day mortality in AH. CONCLUSIONS: Taken together, these data indicate that AH is associated with a profound disruption of complement. Inclusion of complement, especially CFI and sC5b9, along with other laboratory indicators, could improve diagnostic and prognostic indications of disease severity and risk of mortality for AH patients.

Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 patients.

SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID-19. We investigated whether the specific immune responses in the peripheral blood of 276 patients were associated with the severity and progression of COVID-19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56- CD16+ NK-cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID-19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic intervention.

Vascular Endothelial Growth Factor-A Is Associated with Platelets and Complement 4 in Patients with Primary Sjögren's Syndrome.

OBJECTIVE: We aimed at investigating the expression level of vascular endothelial growth factor-A (VEGF-A) in patients with primary Sjögren's Syndrome (pSS) and evaluating the relationship between serum VEGF-A and the laboratory indicators that are associated with it in pSS. METHODS: The VEGF-A levels were measured by ELISA in a total of 88 participants, including 58 patients with pSS and 30 healthy people. The VEGF-A levels between two groups were analyzed. RESULTS: The serum levels of VEGF-A in pSS and control groups were 175.50 (112.00,296.50) pg/mL and 181.50 (155.25,288.50) pg/mL, without statistically significant difference. The associations were found between serum levels of VEGF-A with C reactive protein (CRP) (r=0.265, P<0.05), white blood cells (WBC) (r=0.302, P<0.05), neutrophils (NEUT) (r=0.349, P<0.05), platelets(PLT) (r=0.276, P<0.05), complement 3 (C3) (r=0.477, P<0.05), complement 4 (C4) (r=0.387, P<0.05) and CA19-9 (r=0.392, P<0.05). Among these laboratory indicators, VEGF-A was correlated with platelets and complement 4 in patients with pSS. CONCLUSIONS: In patients with pSS, the levels of VEGF-A were independently influenced by the levels of platelet and complement 4, which indicated the intermodulation between the growth factor and immune system in the autoimmune disease.

Plasma C4d Correlates With C4d Deposition in Kidneys and With Treatment Response in Lupus Nephritis Patients.

Objective: To examine whether C4d plasma levels correlate with treatment response and C4d kidney deposition in systemic lupus erythematosus (SLE) with lupus nephritis (LN). Methods: C4d plasma levels were analyzed by a unique assay specifically detecting C4d arising from complement activation and C4 plasma levels were quantified with competitive ELISA. SLE patients with LN (71) and active SLE patients without LN (22) plus 145 controls were included. For 52 LN patients samples were available both at baseline and after immunosuppressive treatment. C4d kidney deposition was detected using immunohistochemistry in two matching kidney biopsies of 12 LN patients. Results: In comparison to population-based controls, plasma C4d levels were significantly increased in SLE patients (0.33 mg/L versus 0.94 mg/ml, p < 0.0001) with significantly higher levels in LN patients (1.02 mg/L) than in non-renal SLE patients (0.57 mg/L, p = 0.004). The C4d/C4 ratio was also significantly higher in LN (11.2) than in non-renal SLE patients (2.5, p = 0.0002). According to ROC curve analysis, C4d was found to be an accurate marker to discriminate LN from non-renal SLE patients (p = 0.004). The C4d/C4 ratio displayed even higher specificity, sensitivity and overall accuracy as marker for LN than C4d and C4 alone. At baseline, C4d levels correlated significantly with urine-albumin to creatinine ratio (rs = 0.43, p = 0.011) and with renal activity index (rs = 0.37, p = 0.002). Immunohistochemical staining showed glomerular deposits of C4d in kidney biopsies, which strikingly correlated with plasma C4d levels (rs = 0.7, p = 0.0002). Plasma C4d declined significantly after treatment in patients that experienced favorable clinical and histopathological response (p < 0.0001), while levels remained mainly unchanged in non-responders. Conclusion: Plasma C4d discriminates LN from active non-renal SLE, correlates with C4d kidney deposits and appears valuable in monitoring responsiveness to various treatments. The C4d/C4 ratio might be superior to C4d alone.

Measurement of serum interferon alpha in Egyptian patients with systemic lupus erythematosus and evaluation of its effect on disease activity: a case-control study.

Much evidence highlighted the role of interferon alpha (IFN-α) in systemic lupus erythematosus (SLE) and suggested its possible role in assessing disease activity. We measured serum IFN-α in Egyptian SLE patients in order to determine a cutoff value that can be used to distinguish patients from healthy controls and explored its clinical value in monitoring disease activity and different aspects of the disease, in particular lupus nephritis. This cross-sectional, case-control study was conducted on 59 SLE patients and 30 healthy controls. Serum IFN-α was measured in all participants using sensitive enzyme-linked immunosorbent assay (ELISA). SLE patients underwent assessment of disease activity using the SLE disease activity index-2000 (SLEDAI-2K) as well as an evaluation of proteinuria, complement C3 and C4, and serology. Patients with evidence of renal involvement underwent renal biopsy. The median serum IFN-α was 81.8 pg/mL (interquartile range [IQR] 63.4:102.4), which was significantly higher than in healthy controls (median 10.3 pg/mL [IQR 7.3:11.6]) (p<0.001). At serum level of 14.7 pg/mL, IFN-α has high sensitivity and specificity to discriminate SLE patients from controls, with high positive and negative predictive values. Serum IFN-α was not associated with markers of disease activity, clinical features and anti-double stranded DNA. Furthermore, it was not associated with markers of renal activity, including proteinuria, C3 and C4 complement factors and histopathology renal classes. Despite elevated levels of serum IFN-α in SLE patients, it is not possible to use it as a biomarker for disease activity.

Association of anticardiolipin antibodies, complement and leptin with the severity of coronary artery disease expressed as syntax score.

Chronic inflammation plays a role in all stages of atherosclerosis leading to coronary artery disease (CAD), with elevated inflammatory markers being associated with the worse clinical outcome. The goal of the current study was to examine possible association between pro-inflammatory/pro-coagulant factors; anticardiolipin (aCL) autoantibodies, complement C3, C4 and leptin, and the severity of CAD expressed as SYNTAX score. Patients with symptoms of cardiac ischemia undergoing coronary angiography were recruited, and their blood levels of aCL-IgG, aCL-IgM, complement C3, C4 and leptin were assessed. Their association with the SYNTAX score, calculated based on coronary angiography findings, was analyzed. All patients had aCL antibody titer within the normal range. A significant positive association was found for aCL-IgG and SYNTAX score. Male patients had higher average aCL-IgG concentration and SYNTAX score than female patients. No association was found between SYNTAX score and C3 and C4. On the other hand, leptin was negatively associated with SYNTAX score. Our study demonstrates an association between the extent of CAD and aCL-IgG even in the absence of systemic autoimmune disease and at the aCL-IgG levels that are within the normal range. Also, association of lower leptin levels with more severe CAD suggests that its pro-inflammatory effects might not contribute to the pathogenesis of CAD, and that leptin might even exert protective effects on coronary vasculature.

Analysis of antinuclear antibody titers and patterns by using HEp-2 and primate liver tissue substrate indirect immunofluorescence assay in patients with systemic autoimmune rheumatic diseases.

BACKGROUND: Indirect immunofluorescence assay (IIFA) is viewed as a preliminary standard to assess antinuclear antibodies (ANAs). Our aim was to explore ANA positivity rate, titers, and patterns in patients with systemic autoimmune rheumatic diseases (SARD), including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), systemic sclerosis (SSc), and mixed connective tissue disease (MCTD), compared with healthy controls (HC). METHODS: Assess antinuclear antibody titers and patterns were retrospectively identified and compared by IIFA using human epithelial cells (HEp-2) and primate liver tissue substrate according to international consensus in SARD. Serum complement 3 (C3), C4, and immunoglobulin G were compared among subgroups with different ANA titers. The positive predictive values (PPV) for different ANA titers were calculated. RESULTS: There were a total of 3510 samples, including 2034 SLE, 973 RA, 155 SSc, 309 pSS, and 39 MCTD cases. There was no difference in age between HC and SARD, excluding RA. ANA positivity rate in SARD and HC was 78.7% and 12.2%, respectively. A titer of ≥1:320 revealed a PPV of 84.0% in SARD. SLE patients with ANA titers ≥1:320 had significantly lower levels of C3 and C4. AC-4 (31.2%) was the major pattern in patients with SARD, followed by AC-5 (23.9%) and AC-1 (18.8%). SLE mostly presented with AC-4 (30.3%). Several mixed patterns provided a significant hint for SSc and SLE. The major pattern in HC was AC-2 (12.2%). CONCLUSIONS: Assess antinuclear antibody positivity, titers, and patterns display differences in various SARD, contributing to the classification of SARD.