Dietary Sodium, Potassium, and Sodium to Potassium Ratio in Patients With Systemic Lupus Erythematosus

Purpose: The aim of this study was to investigate the association between dietary sodium, potassium, and sodium:potassium ratio and clinical disease activity parameters, damage accrual, and cardiovascular disease risk factors in a population of patients with systemic lupus erythematous (SLE). Research design and study sample: A cross-sectional study including a total of 280 patients was conducted (90.4% females; mean age 46.9 ± 12.85 years). Data collection: The SLE Disease Activity Index (SLEDAI-2K) and the SDI Damage Index were used to assess disease activity and disease-related damage, respectively. A 24-hour diet recall was used to estimate dietary intake of sodium and potassium. Results: Dietary sodium intake was significantly associated with anti-dsDNA ( β = −.005; 95% CI [.002 .008]; p = .001) and complement C4 level ( β = −.002; 95% CI [−.003, .000]; p = .039). Dietary potassium intake was also significantly associated with complement C3 level ( β = −.004; 95% CI [−.007, −.001]; p = .021). Multiple logistic regression models revealed a positive association between dietary sodium intake and the risk of having hsCRP > 3 ( p = .005) and an inverse association between dietary potassium intake and the risk of having hsCRP > 3 ( p = .004). Conclusions: SLE patients with higher dietary sodium and lower dietary potassium intakes had an increased risk of higher hsCRP. Dietary sodium intake was significantly associated with anti-dsDNA and complement C4 level, while dietary potassium intake was associated with complement C3 level, supporting that dietary sodium and potassium intakes might play a key role in markers related to disease activity in SLE patients.

Complement C4-A and Plasminogen as Potential Biomarkers for Prediction of Papillary Thyroid Carcinoma

BackgroundEarly diagnosis and therapy of papillary thyroid carcinoma (PTC) is essential for reducing recurrence and improving the long-term survival. In this study, we aimed to investigate the proteome profile of plasma and screen unique proteins which could be used as a biomarker for predicting PTC.MethodsSerum samples were collected from 29 PTC patients and 29 nodular goiter (NG) patients. Five PTC serum samples and five NG serum samples were selected for proteome profiles by proteomics. Eight proteins in PTC and NG serum samples were selected for confirmation by enzyme-linked immunosorbent assay analysis. Receiver operating characteristic curves was used to evaluate the diagnostic value of potential biomarkers.ResultsComplement C4-A (C4A) and plasminogen (PLG) were significantly lower in serum samples of PTC patients compared with NG patients. C4A was observed to have excellent diagnostic accuracy for PTC, with a sensitivity of 91.67% and specificity of 83.33%. The diagnostic value of PLG for PTC was demonstrated by a sensitivity at 87.50% and specificity at 75.00%. The AUC for C4A and PLG was 0.97 ± 0.02 and 0.89 ± 0.05.ConclusionC4A and PLG appeared to be excellent potential biomarkers for the prediction of PTC.

Parkinson’s Disease-Related Biomarkers That May Appear in Amphetamine Abusers

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. Amphetamine addiction may cause serious of psychotic and physical damage to humans. There is some evidence that shows that amphetamine may increase the risk of PD. Thus, this study is aimed at comparing the PD serum biomarkers between amphetamine addicts and PD patients and utilizing them as diagnostic biomarkers for the early detection of PD incidence among amphetamine addicts. In the current study, nineteen amphetamine addicts, aged <40, were recruited from the Al Amal Psychiatric hospital, Jazan, Saudi Arabia. Nineteen PD patients and 19 healthy controls, who have never taken amphetamine, were also recruited. Blood samples were withdrawn from all groups. A biomarker multiplex assay from MILLIPLEX was used to assess the levels of serum amyloid-P (SAP), complement C4, C-reactive protein (CRP), and CRP/albumin ratio in serum samples (Vitros 350® slide was used to assess the albumin). All data were statistically analyzed using one-way ANOVA. The results showed that SAP and CRP levels were significantly higher in amphetamine addicts compared to healthy controls ( p = 0.0001 and p = 0.0001 , respectively). The results of amphetamine addicts were comparable to PD levels. However, there are no significant differences between all studied groups concerning complement C4 level. Moreover, albumin levels were significantly decreased and CRP/Albumin ratio levels were significantly increased in amphetamine addicts ( p = 0.01 and p = 0.041 , respectively) in contrast with controls. These findings indicate that the increased level of these inflammatory biomarkers (SAP and CRP) in the amphetamine addicts may give a potential possibility of their serum level to be used as screening markers to detect PD development in the amphetamine addict. It may be useful to evaluate the changes in easily accessible and cost-effective parameters such as the serum CRP/albumin ratio.

Complement C4 Is Reduced in iPSC-Derived Astrocytes of Autism Spectrum Disorder Subjects

In recent years, accumulating evidence has shown that the innate immune complement system is involved in several aspects of normal brain development and in neurodevelopmental disorders, including autism spectrum disorder (ASD). Although abnormal expression of complement components was observed in post-mortem brain samples from individuals with ASD, little is known about the expression patterns of complement molecules in distinct cell types in the developing autistic brain. In the present study, we characterized the mRNA and protein expression profiles of a wide range of complement system components, receptors and regulators in induced pluripotent stem cell (iPSC)-derived neural progenitor cells, neurons and astrocytes of individuals with ASD and neurotypical controls, which constitute in vitro cellular models that recapitulate certain features of both human brain development and ASD pathophysiology. We observed that all the analyzed cell lines constitutively express several key complement molecules. Interestingly, using different quantification strategies, we found that complement C4 mRNA and protein are expressed in significantly lower levels by astrocytes derived from ASD individuals compared to control astrocytes. As astrocytes participate in synapse elimination, and diminished C4 levels have been linked to defective synaptic pruning, our findings may contribute to an increased understanding of the atypically enhanced brain connectivity in ASD.

Complement C4, Infections, and Autoimmune Diseases

Complement C4, a key molecule in the complement system that is one of chief constituents of innate immunity for immediate recognition and elimination of invading microbes, plays an essential role for the functions of both classical (CP) and lectin (LP) complement pathways. Complement C4 is the most polymorphic protein in complement system. A plethora of research data demonstrated that individuals with C4 deficiency are prone to microbial infections and autoimmune disorders. In this review, we will discuss the diversity of complement C4 proteins and its genetic structures. In addition, the current development of the regulation of complement C4 activation and its activation derivatives will be reviewed. Moreover, the review will provide the updates on the molecule interactions of complement C4 under the circumstances of bacterial and viral infections, as well as autoimmune diseases. Lastly, more evidence will be presented to support the paradigm that links microbial infections and autoimmune disorders under the condition of the deficiency of complement C4. We provide such an updated overview that would shed light on current research of complement C4. The newly identified targets of molecular interaction will not only lead to novel hypotheses on the study of complement C4 but also assist to propose new strategies for targeting microbial infections, as well as autoimmune disorders.

Complement 4 Aids in Prediction of Newly Diagnosed Multiple Myeloma Outcome in Patients

Background and aim: A cure for the heterogeneous hematological malignancy Multiple Myeloma (MM) is yet to be developed. To date, the early risk factors associated with poor outcomes in MM have not been fully elucidated. Studies have shown an aberrant complement system in MM patients, but the precise association necessitates elucidation. Therefore, this study scrutinizes the correlation between serum complement level and the disease outcome of MM patients.Materials and methods: A retrospective analysis of 72 MM patients (new diagnosis) with complement C4 and C3 along with common laboratory indicators was done. The Pearson’s χ2 test and the Mann–Whitney U test were done to evaluate categorical or binary variables and inter-group variance, respectively. Kaplan-Meier test and Cox’s proportional hazards regression were employed for quantitation of overall survival (OS) and univariate or multivariate analyses, respectively.Results: The Cox proportional hazard model analysis unveiled the following: platelet≤115.5×10^9/L(HR=5.82，95%CI=2.522-13.436, P<0.001)， complement C4≤0.095g/L(HR=3.642, 95%CI=1.486-8.924,P=0.005), age≥67 years(HR=0.191, 95%CI=0.078-0.47, P<0.001)，bone marrow plasma cell percentage≥30.75% (HR=0.171, 95%CI=0.06-0.482, P=0.001) can be employed as independent predictors of OS. Of these, advanced age, low platelet level, and a high proportion of bone marrow plasma cells have been implicated in poor outcomes in MM patients. Interestingly, a low complement 4 level can function as a new indicator of poor prognosis in MM patients.Conclusion: Low levels of C4 are indicative of a poor outcome in newly diagnosed MM patients.

Complement C4 is Reduced in iPSC-Derived Astrocytes of Autism Spectrum Disorder Subjects

In recent years, accumulating evidence has shown that the innate immune complement system is involved in several aspects of normal brain development and in neurodevelopmental disorders, including autism spectrum disorder (ASD). Although abnormal expression of complement components was observed in post-mortem brain samples from individuals with ASD, little is known about the expression patterns of complement molecules in distinct cell types in the developing autistic brain. In the present study, we characterized the mRNA and protein expression profiles of a wide range of complement system components, receptors and regulators in induced pluripotent stem cell (iPSC)-derived neural progenitor cells, neurons and astrocytes of individuals with ASD and neurotypical controls, which constitute in vitro cellular models that recapitulate certain features of both the human brain development and ASD pathophysiology. We observed that all the analyzed cell lines constitutively express several key complement molecules. Interestingly, using different quantification strategies, we found that complement C4 mRNA and protein are expressed in significantly lower levels by astrocytes derived from ASD individuals compared to control. As astrocytes participate in synapse elimination and diminished C4 levels have been linked to defective synaptic pruning, our findings may contribute to an increased understanding of the atypically enhanced brain connectivity in ASD.

MALDI-TOF Protein Profiling Reflects Changes in Type 1 Diabetes Patients Depending on the Increased Amount of Adipose Tissue, Poor Control of Diabetes and the Presence of Chronic Complications

Introduction: Protein profiling allows the determination of the presence of proteins marking various stages of the disease, and differentiates between people at risk of various diseases. In type 1 diabetes, protein profiling had been previously used to find blood markers other than islet autoantibodies to indicate the pancreatic beta cell destruction process and to reflect the progression of type 1 diabetes mellitus (T1DM). However, T1DM is an auto-immune disease and its clinical presentation changes in time of its duration. The aim of the study: To find differences in protein profiles in patients with type 1 diabetes according to diabetes control (HbA1c > 7%) and with presence of diabetic complications or obesity. It may help to identify subgroups of patients who may need a better clinical supervision and individualized treatment. Material and methods: A group of 103 patients with auto-immunologically confirmed T1DM, and meeting the following inclusion criteria: Caucasian race, duration of diabetes >5 years, were used in the study. Criteria of exclusion: past or present cancer (treated with chemo-/radiotherapy), diseases of the liver (ALT > 3 × ULN) except for people with simple hepatic steatosis, chronic renal disease (eGFR < 30 mL/1.73 m2/min), and acute inflammation (CRP > 5 mg/dL). The study group was divided in terms of the presence of chronic complications, obesity, or poor metabolic control (HbA1c > 7%). Protein profiling was completed by using the MALDI-TOF MS (matrix-assisted laser desorption/ionization-time of flight mass spectrometry) analyzer. Results: Differentiating proteins were identified in all of the groups. The groups burdened with complications, obesity, and poor metabolic control were characterized by increased levels of fibrinogen, complement C4 and C3. Conclusion: The groups of type 1 diabetes patients burdened with complications, obesity, and poor metabolic control were characterized by increased levels of fibrinogen, complement C4 and C3. Further detailed studies are necessary to determine more subtle changes in the proteomic profile of patients with type 1 diabetes.