Exploring the Correlation between Interleukin-17A Promoter Polymorphism at its -197 G/A and Rheumatoid Arthritis: Impact on Disease Severity and Activity.

T helper 17 (Th17) cells have been reported to be the most powerful factor in autoimmune disorder pathogenesis, which points to the Th17 master cytokine, interleukin (IL)-17A, as the crucial mediator. We aimed to determine the impact of IL-17A polymorphism in the -197 G/A promoter region on level of IL-17 and intensity of rheumatoid arthritis (RA) disease symptoms. This case-control study was conducted at the Department of Clinical Rheumatology of Aswan university Hospital and included 35 people suffering RA and 30 volunteer controls, matched for age and sex. Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, erythrocyte sedimentation rate (ESR), serum IL-17, and C-reactive protein (CRP) were measured in the RA patient group. Restriction fragment length polymorphism (RFLP) was conducted by polymerase chain reaction (PCR) amplicon obtained by IL-17A -197 G /A primers. Of the 35 RA patients, RF was positive in 33 (94.29%) and anti-CCP antibodies in 25 (71.43%), CRP in 31 (88.57%). Of the 35 RA patients, 5 (14.29%) patients carried the G/G genotype, 18 (51.43%) G/A and 12 (34.29%) A/A. IL-17 serum level was significantly greater in the more active RA (DAS28 >5.1) group than the less active (DAS28 ≤5.1) group. Of the RA patients carrying wild type G/G genotype, 60% had more active disease (DAS 28> 5.1), as compared to those with lower activity (DAS 28 ≤5.1), 40% carried the wild type G/G genotype. In conclusion, the study findings imply that IL-17A gene polymorphism is connected to RA clinical severity rather than with RA susceptibility.

The role of pentraxin 3 and oxidative status in the prognosis of multiple myeloma.

Multiple myeloma (MM) is a bone marrow malignancy characterized by plasma cell proliferation. It was aimed to investigate pentraxin 3 (PTX3) levels, oxidative/antioxidative status, and their correlation in MM. In the study, four groups were established, including newly diagnosed MM (NDMM), MM in remission (Rem-MM), relapsed/refractory MM (RRMM) patients, and a healthy control group. PTX3 levels were measured using enzyme-linked immunosorbent assay, and the total antioxidant status (TAS) and total oxidant status (TOS) were assessed with an autoanalyzer. The oxidative stress index (OSI) was calculated using the formula: OSI (arbitrary unit) = TOS (µmol H2O2 Eq/L)/TAS (mmol Trolox Eq/L) × 100. The study involved comparing PTX3, TAS, TOS, and OSI levels among these four groups. PTX3 levels were significantly elevated in NDMM and RRMM groups compared to controls and the Rem-MM group (NDMM vs control; p < 0.001, NDMM vs Rem-MM; p < 0.001, RRMM vs control; p < 0.001, and RRMM vs Rem-MM; p = 0.006). TAS was higher in NDMM and RRMM groups versus controls (p = 0.009 and p < 0.001, respectively), and TOS was higher in rem-MM group versus NDMM and control groups (p < 0.001 and p = 0.016, respectively). OSI was higher in the Rem-MM group than in NDMM and RRMM groups (p < 0.001 and p = 0.009, respectively). Multivariate analysis confirmed associations between MM groups and PTX3 levels. Receiver operating characteristic analysis revealed high specificity (90%) and sensitivity (79%) for PTX3 in NDMM at a >0.56 ng/mL cut-off value. This study suggests that PTX3 levels may have diagnostic and prognostic potential in MM and its relationship with oxidative stress requires further exploration.

Pretransplantation Inflammatory and Nutritional Status in Elderly Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Value of C-Reactive Protein-to-Albumin Ratio.

There are no clear criteria for selecting elderly patients with hematologic malignancies eligible for allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to evaluate inflammatory and nutritional status biomarkers as prognostic indicators of allogeneic HSCT in elderly patients. We compared the prognostic effects of 4 representative pretransplantation biomarkers: C-reactive protein-to-albumin ratio (CAR), Glasgow Prognostic Score (GPS), prognostic nutritional index (PNI), and albumin-to-globulin ratio (AGR). A total of 143 patients age ≥60 years who underwent their first allogeneic HSCT for a hematologic malignancy were enrolled between 2010 and 2020 in our single-center cohort. The median patient age was 65 years (range, 60 to 72 years). Pretransplantation high CAR, high GPS, and low PNI scores were associated with poor overall survival (OS), but the AGR was not associated with OS. Among the 4 biomarkers, CAR stratified OS most significantly (P < .001). Multivariate analyses identified only high CAR as an independent prognostic factor associated with OS (hazard ratio [HR], 1.98; P = .031) and showed that a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score ≥3 also was associated with OS (HR, 2.04; P = .012). High CAR was correlated with poor performance status, male sex, and high Disease Risk Index, but not with high HCT-CI score. When the patients were stratified into 3 groups according to a composite risk assessment using CAR and HCT-CI, the 3-year OS decreased significantly with increasing scores (82.8%, 50.3%, and 27.0%, respectively; P < .0001). In conclusion, CAR is the most useful prognostic indicator among the inflammatory and nutritional status biomarkers for allogeneic HSCT in elderly patients. Inflammatory and nutritional status in the elderly may be important prognostic factors for allogeneic HSCT independent of HCT-CI score.

Association between serum C-reactive protein (CRP) and Omicron variant COVID-19 pneumonia in cancer patients: A multicenter cross-sectional study at the end of 2022 in China.

Cancer patients with COVID-19 have a higher infection rate and mortality rate than non-cancer patients. However, there are few studies on the correlation between the serum C-reactive protein (CRP) and cancer patients with COVID-19. This study aims to investigate the association between serum CRP and the incidence of COVID-19 pneumonia in cancer patients at the end of 2022 in China. This cross-sectional study with a retrospective cohort between December 2022 and February 2023 assessed cancer patients complicated with COVID-19 infection in 2 Chinese institutions. Logistic regression analyses were used to compute Odds ratio (OR) and 95%CIs for the association between serum CRP and the incidence of COVID-19 pneumonia in cancer patients. A total of 213 cancer patients with COVID-19 were enrolled. Eighty-six patients (40.4%) developed COVID-19 pneumonia, among which 23 patients (10.8%) progressed to severe cases. Univariate Logistic regression showed that high CRP levels were found to be an unfavorable predictor of COVID-19 outcomes (OR = 17.9, 95%CI: 7.3, 43.6; P < .001). In the multivariate analysis, high CRP levels were associated with a higher incidence rate of COVID-19 pneumonia (OR = 9.8, 95%CI: 2.2, 43.8; P = .003). In the multivariate logistic regression model and smooth curve fitting, we found a correlation between CRP and COVID-19 pneumonia. The serum CRP was associated with the incidence of Omicron variant COVID- 19 pneumonia in cancer patients. Hence, cancer patients with high CRP level maybe need for timely computer tomography examination and more aggressive treatment.

Biomimetic affinity membrane roll column for rapid purification of C-reactive protein.

To in-depth explore the action mechanism of C-reactive protein (CRP) and precisely study its signaling pathways, it is essential to acquire high-purity CRP while preserving its intact structure and functionality. In this study, we propose and fabricate a high-density 2-methacryloyloxyethyl phosphorylcholine (MPC)-modified membrane roll column (MPC-MRC) using a surface-initiated atom transfer radical polymerization (SI-ATRP) approach, which can overcome these limitations (long incubation time and low adsorption capacity) of conventional enrichment materials. The MPC-MRC incorporates a high-density 2-hydroxyethyl methacrylate polymer brush to prevent non-specific protein adsorption and multiple MPC polymer brush layers for high-performance enrichment of CRP in the company of calcium ions. Furthermore, the MPC-MRC exhibits high permeability, hydrophilicity, and mechanical strength. Compared to previous technologies, this novel material demonstrates significantly higher CRP binding capacity (310.3 mg/g), shorter processing time (only 15 min), and lower cost (only 12 USD/column). Notably, the MPC-MRC enables fast and effective purification of CRP from both human and rat serum, exhibiting good selectivity, recovery (> 91.3 %), and purity (> 95.2 %). Thus, this proposed purification approach based on MPC-MRC holds great potential for target protein enrichment from complex samples, as well as facilitating in-depth studies of its biological functions.

Structural insights into the biological functions of the long pentraxin PTX3.

Soluble pattern recognition molecules (PRMs) are a heterogenous group of proteins that recognize pathogen- and danger-associated molecular patterns (PAMPs and DAMPs, respectively), and cooperate with cell-borne receptors in the orchestration of innate and adaptive immune responses to pathogenic insults and tissue damage. Amongst soluble PRMs, pentraxins are a family of highly conserved proteins with distinctive structural features. Originally identified in the early 1990s as an early inflammatory gene, PTX3 is the prototype of long pentraxins. Unlike the short pentraxin C reactive protein (CRP), whose expression is mostly confined to the liver, PTX3 is made by several immune and non-immune cells at sites of infection and inflammation, where it intercepts fundamental aspects of infection immunity, inflammation, and tissue remodeling. Of note, PTX3 cross talks to components of the complement system to control cancer-related inflammation and disposal of pathogens. Also, it is an essential component of inflammatory extracellular matrices (ECMs) through crosslinking of hyaluronic acid and turn-over of provisional fibrin networks that assemble at sites of tissue injury. This functional diversity is mediated by unique structural characteristics whose fine details have been unveiled only recently. Here, we revisit the structure/function relationships of this long pentraxin in light of the most recent advances in its structural biology, with a focus on the interplay with complement and the emerging roles as a component of the ECM. Differences to and similarities with the short pentraxins are highlighted and discussed.

Point-of-care biomarker assay for rapid multiplexed detection of CRP and IP-10.

Rapid and accurate measurements of immune protein markers are essential for diagnosis and treatment in all clinical settings. The recent pandemic has revealed a stark need for developing new tools and assays that could be rapidly used in diverse settings and provide useful information to clinicians. Here, we describe the development and test application of a novel one-step CRP/IP-10 duplex assay for the LightDeck platform capable of delivering reproducible and accurate measurements in under eight minutes. We used the optimized assay to measure CRP and IP-10 levels in human blood and serum samples from healthy, SARS-CoV-2 (COVID-19) positive, and influenza-like illness (ILI) presenting patients. Our results agreed with previously published analyte levels and enabled us to make statistically significant comparisons relevant to multiple clinical parameters. Our duplex assay is a simple and powerful tool for aiding prognostic decision-making in diverse settings.

Value of increased CRP/albumin ratio in predicting embolic events in patients with infective endocarditis.

Background: The CRP/albumin ratio (CAR), a new inflammatory marker, is associated with adverse outcomes in various cardiovascular diseases. We evaluated the effectiveness of CAR in predicting embolic events in patients diagnosed with infective endocarditis (IE). Methods: A total of 145 patients with IE were included in the study and categorized into two groups according to the presence of embolic events. We retrospectively analyzed the patients' clinical, laboratory and echocardiographic data. Results: CRP (94.2 vs 63.3; p < 0.001) and CAR (25.8 vs 15.1; p < 0.001) values were significantly higher in patients who experienced embolic events. Multivariate analysis showed that a high CAR value (odds ratio: 1.030; 95% CI: 1.000-1.060; p = 0.041) was an independent predictor of embolic events in patients with IE. Conclusion: The CAR is a cheap and easily accessible marker that can predict the development of embolic events in patients diagnosed with IE.

Association of mTOR Pathway and Conformational Alterations in C-Reactive Protein in Neurodegenerative Diseases and Infections.

Inflammatory biomarkers have been very useful in detecting and monitoring inflammatory processes along with providing helpful information to select appropriate therapeutic strategies. C-reactive protein (CRP) is a nonspecific, but quite useful medical acute inflammatory biomarker and is associated with persistent chronic inflammatory processes. Several studies suggest that different levels of CRP are correlated with neurological disorders such as Alzheimer's disease (AD). However, dynamics of CRP levels have also been observed in virus/bacterial-related infections leading to inflammatory responses and this triggers mTOR-mediated pathways for neurodegeneration diseases. The biophysical structural transition from CRP to monomeric CRP (mCRP) and the significance of the ratio of CRP levels on the onset of symptoms associated with inflammatory response have been discussed. In addition, mTOR inhibitors act as immunomodulators by downregulating the expression of viral infection and can be explored as a potential therapy for neurological diseases.

Monomeric C-reactive protein: A novel biomarker predicting neurodegenerative disease and vascular dysfunction.

Circulating C-reactive protein (pCRP) concentrations rise dramatically during both acute (e.g., following stroke) or chronic infection and disease (e.g., autoimmune conditions such as lupus), providing complement fixation through C1q protein binding. It is now known, that on exposure to the membranes of activated immune cells (and microvesicles and platelets), or damaged/dysfunctional tissue, it undergoes lysophosphocholine (LPC)-phospholipase-C-dependent dissociation to the monomeric form (mCRP), concomitantly becoming biologically active. We review histological, immunohistochemical, and morphological/topological studies of post-mortem brain tissue from individuals with neuroinflammatory disease, showing that mCRP becomes stably distributed within the parenchyma, and resident in the arterial intima and lumen, being "released" from damaged, hemorrhagic vessels into the extracellular matrix. The possible de novo synthesis via neurons, endothelial cells, and glia is also considered. In vitro, in vivo, and human tissue co-localization analyses have linked mCRP to neurovascular dysfunction, vascular activation resulting in increased permeability, and leakage, compromise of blood brain barrier function, buildup of toxic proteins including tau and beta amyloid (Aß), association with and capacity to "manufacture" Aß-mCRP-hybrid plaques, and, greater susceptibility to neurodegeneration and dementia. Recently, several studies linked chronic CRP/mCRP systemic expression in autoimmune disease with increased risk of dementia and the mechanisms through which this occurs are investigated here. The neurovascular unit mediates correct intramural periarterial drainage, evidence is provided here that suggests a critical impact of mCRP on neurovascular elements that could suggest its participation in the earliest stages of dysfunction and conclude that further investigation is warranted. We discuss future therapeutic options aimed at inhibiting the pCRP-LPC mediated dissociation associated with brain pathology, for example, compound 1,6-bis-PC, injected intravenously, prevented mCRP deposition and associated damage, after temporary left anterior descending artery ligation and myocardial infarction in a rat model.

Prediction of coronary artery lesions based on C-reactive protein levels in children with Kawasaki Disease: a retrospective cohort study.

OBJECTIVE: Since coronary artery lesions (CALs) are the most severe complication of Kawasaki disease (KD), clinically speaking, early prediction of CALs is crucial. The authors aimed to investigate the predictive value of C-reactive protein (CRP) in predicting CALs in KD patients. METHODS: KD patients were divided into the CALs group and the non-CALs group. The clinical and laboratory parameters were collected and compared. Multivariate logistic regression analysis was used to determine the independent risk factors of CALs. The receiver operating characteristic curve was applied to determine the optimal cut-off value. RESULTS: 851 KD patients who met the inclusion criteria were studied, including 206 in the CALs group and 645 in the non-CALs group. Children in the CALs group had significantly higher CRP levels than the non-CALs group (p < 0.05). Multivariable logistic regression analysis showed that incomplete KD, male, lower hemoglobin, and higher CRP were independent risk factors for predicting CAL (all p < 0.05). The optimal cut-off value of initial serum CRP for predicting CALs was 105.5 mg/L, with a sensitivity of 47.57% and a specificity of 69.61%. In addition, KD patients with high CRP (≥105.5 mg/L) had a higher occurrence of CALs than those with low CRP (<105.5 mg/L) (33% vs 19%, p < 0.001). CONCLUSION: The incidence of CALs was significantly higher in patients with high CRP. CRP is an independent risk factor for CALs formation and may be useful for predicting CALs in KD patients.

An interaction between the inflammatory condition and the hypercoagulable condition occurs in primary Sjögren syndrome.

This study aimed to assess the D-dimer level in patients with primary Sjögren syndrome (pSS), uncover its relationship with clinical symptoms, and appraise its predictive value in discriminating disease activity. The laboratory parameters of 101 consecutive patients with pSS and 101 healthy controls were analyzed and compared. Patients were divided into two subgroups according to their D-dimer levels, for the comparison of clinical features. Pearson's correlations were used to measure the relationships between D-dimer levels and other variables. The area under the curve (AUC) was calculated to predict disease activity. The erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP) level, and D-dimer level were each higher in patients with pSS than in healthy controls. Compared with the low-D-dimer-level patients, those with elevated D-dimer levels exhibited higher ESRs (p < 0.0001) and higher levels of hsCRP (p < 0.0001), fibrinogen (p < 0.0001), and immunoglobulin A (p = 0.002). Cases with elevated D-dimer levels were prone to be more severe, based on ESSDAI evaluation (p < 0.0001). Patients with higher D-dimer levels had more articular involvement (p < 0.0001), which was significantly correlated with both the ESR (r = 0.21, p = 0.03) and hsCRP level (r = 0.56, p = 0.001). The D-dimer level may help to discriminate low disease activity from moderate/high disease activity (AUC = 0.754). The D-dimer level was correlated positively with both the ESR and hsCRP level in patients with pSS. The ESR and levels of hsCRP, fibrinogen, and disease activity were higher in the elevated D-dimer level group. The D-dimer level was demonstrated to have predictive value in differentiating pSS disease activity. Key Points •D-Dimer was higher in patients with pSS. •D-Dimer may help for predicting the disease activity in patients with pSS.

Clinical outcomes of unilateral biportal endoscopic lumbar interbody fusion (ULIF) compared with conventional posterior lumbar interbody fusion (PLIF).

BACKGROUND CONTEXT: In recent years, unilateral biportal endoscopic lumbar interbody fusion (ULIF) has been more and more favored by spinal surgeons because of its advantages of low trauma, rapid recovery, high fusion rate and fewer complications. PURPOSE: To compare the clinical effects of ULIF with those of conventional open posterior lumbar interbody fusion (PLIF). STUDY DESIGN: Prospective case control study. PATIENT SAMPLE: Twenty-seven patients treated by ULIF and thirty-three patients treated by PLIF. OUTCOME MEASURES: The preoperative baseline and surgical technique-related outcomes (mean operation time, blood loss during operation, postoperative drainage, and postoperative hospital stay) were compared between the two groups. The clinical status of the two groups before and after surgery were also compared: visual analogue scale (VAS) score of the legs and back, Japanese Orthopedic Association (JOA) score and Oswestry Disability Index (ODI). The clinical laboratory indexes of the two groups before and after the operation were compared: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), creatine phosphokinase (CPK), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), as well as the incidence of complications, such as dural tear, nerve root injury and infection. METHODS: Adult patients who underwent L3-S1 single level lumbar interbody fusion were included in the study. They were divided into a PLIF group and a ULIF group according to the type of surgery. This study comprised 60 cases: 27 cases in the ULIF group and thirty-three cases in the PLIF group. RESULTS: There was no significant difference in preoperative baseline between the two groups. The ULIF group experienced less blood loss, postoperative drainage and a shorter postoperative hospital stay than the PLIF group; however the ULIF group required a longer operation time than the PLIF group (p<.05). CRP, ESR, CPK, IL-6, and TNF-α levels of the PLIF group were all significantly higher than those of the ULIF group 5 days after surgery (p<.05). The improvements in the VAS scores for back pain, VAS scores for leg pain and JOA score in the ULIF group were all significantly better than those in the PLIF group at 5 days after surgery (p<.05). There was no significant difference in fusion rate at 6 months between the 2 groups (p>.05). CONCLUSIONS: This study showed that ULIF and PLIF were both effective surgical techniques for lumbar interbody fusion. However, ULIF caused less bleeding, reduced inflammatory reaction, less tissue damage and faster postoperative recovery compared with PLIF. Both long-term follow-up and larger clinical studies are needed to validate the clinical and radiological results of this surgery.

Cholesterol-binding sequence is a key regulatory motif of cellular folding and conformational activation for C-reactive protein.

Human, rat, and mouse C-reactive protein (CRP) possess distinct expression patterns, but have similar conformations and conserved in vivo functions. We have previously demonstrated that this level-function mismatch is delicately tuned by the hidden activities of unfolded CRP. The cholesterol-binding sequence (CBS; a.a. 35-47) is a major functional motif exposed on monomeric CRP, which is the unfolded and activated conformation of CRP. We replaced the CBS of rat CRP with that of either mouse or human CRP, yielding two grafting mutants with unaffected pentameric assembly. However, these mutants exhibited altered cellular foldability and conformational activation efficiency that matched those of the CRP that provided the grafted CBS. These results indicate that CBS is a critical regulatory motif, whose variation maintains the pentameric assembly of CRP but derives distinct cellular foldabilities and conformational activation efficiencies, therefore helping to ensure that CRPs with various expression patterns exhibit overall conserved functions.

Carotid contrast-enhanced ultrasonography combined with sirtuin-3 in the diagnosis of plaques in carotid atherosclerosis.

BACKGROUND: Carotid atherosclerosis (CAS) is one of the main causes of ischemic stroke. Currently, the clinical evidence for contrast-enhanced ultrasonography (CEUS) as a method for diagnosing CAS is still inadequate. Sirtuin-3 (SIRT3) is associated with the inflammation response; however, few studies have evaluated SIRT3 in CAS. OBJECTIVES: To investigate the role of SIRT3 in CAS patients and its diagnostic value for unstable plaques when combined with CEUS. MATERIAL AND METHODS: This is a prospective observational study including 517 CAS patients who were admitted to our hospital from January 2015 to December 2020. All patients received a normal Doppler ultrasound, CEUS and magnetic resonance imaging (MRI). The latter was used as the gold standard in evaluating plaque conditions. Serum SIRT3 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-ch), low-density lipoprotein cholesterol (LDL-ch), C-reactive protein (CRP), and interleukin (IL)-6 levels were measured and recorded. RESULTS: Patients with severe CAS showed significantly higher levels of CRP, IL-6, TC, and LDL-ch, a higher frequency of unstable plaques, as well as a lower level of HDL-ch. In patients with severe CAS and CAS patients with stable plaques, the levels of SIRT3 were markedly lower. Patients with a high expression of SIRT3 showed significantly lower levels of CRP, IL-6, TC and LDL-ch, and higher levels of HDL-ch, as well as a lower frequency of unstable plaques. Receiver operating characteristic (ROC) curves showed that the combination of CEUS and SIRT3 could achieve high sensitivity and specificity in the diagnosis of unstable plaques. High levels of C-reactive protein, IL-6, TC, TG and LDL-ch, as well as low levels of SIRT3 and HDL-ch, and current smoking were risk factors of unstable plaques in CAS patients. CONCLUSIONS: A low expression of SIRT3 predicted a higher risk for unstable plaques in CAS patients. The combination of CEUS and SIRT3 is a potential strategy for diagnosing unstable plaques.

The clinical value of high mobility group box-1 and CRP/Alb ratio in the diagnosis and evaluation of sepsis in children.

OBJECTIVE: To explore the clinical value of high mobility group box-1 (HMGB-1), C-reactive protein (CRP), procalcitonin (PCT), and CRP to albumin (Alb) ratio in the diagnosis and evaluation of the severity of sepsis in children. PATIENTS AND METHODS: A total of 90 children, 50 with sepsis and 40 with general infection, whose symptoms did not meet the criteria for diagnosis of sepsis, were admitted to the Pediatrics Department of Jingzhou Central Hospital in Hubei Province between November 2021 and December 2022, were enrolled and selected as experimental and control group, respectively. The serum of two groups was collected within 24 hours after admission, the levels of HMGB-1 were detected by enzyme-linked immunosorbent assay (ELISA), and CRP, PCT, Alb, and hospitalization days were recorded. The differences in indicators between the two groups were compared, and correlation analysis was performed between hospitalization days and various indicators. The receiver operating characteristic (ROC) curve was drawn to evaluate the independent or combined value of CRP, PCT, HMGB-1, and CRP/Alb ratio in the early diagnosis of sepsis in children. RESULTS: These four indicators of children with sepsis were significantly higher than those in the general infection group (all p=0.000). The levels of CRP, PCT and CRP/Alb ratio were significantly positively correlated with the hospitalization days (r=0.329, 0.333, 0.329; p=0.02, 0.01, 0.002). The area under curve (AUC) of CRP, PCT, HMGB-1, and CRP/Alb ratio for the diagnosis of sepsis in children was 0.798, 0.817, 0.838, 0.809, respectively, and that of the combination of four indicators was 0.952. CONCLUSIONS: CRP, PCT, HMGB-1, and CRP/Alb ratio resulted as effective indicators for early diagnosis and evaluation of childhood sepsis, having a higher value in combined diagnosis.

Regulation of Conformational Changes in C-reactive Protein Alters its Bioactivity.

The acute phase C-reactive protein (CRP) is mainly synthesized and secreted by the liver in a cytokine-mediated response to infection or inflammation and circulates as a pentamer (pCRP) in plasma. Recent studies indicate that CRP is not only a marker but is directly involved in inflammation. CRP has a vital role in host defense and inflammation, metabolic function and scavenging through its ability for calcium depended binding to exogenous and endogenous molecules having phosphocholine followed by activation of the classical complement pathway. Accumulating evidence indicates that pCRP dissociates into monomeric CRP (mCRP) and most proinflammatory actions of CRP are only expressed following dissociation of its native pentameric assembly into mCRP. The dissociation of CRP into mCRP altogether promotes the ligand-binding capability. mCRP emerges to be the main conformation of CRP that participates in the regulation of local inflammation, however, little is identified concerning what triggers the significantly enhanced actions of mCRP and their binding to diverse ligands. The separation of mCRP from pCRP may be a direct relationship between CRP and inflammation. Here we review the current literature on CRP dissociation and its interaction with different ligands. The possibility to avoid the generation of the proinflammatory potential of mCRP has driven therapeutic approaches by targeting the dissociation mechanism of pCRP or inhibition of mCRP itself during inflammation.

PTX3 structure determination using a hybrid cryoelectron microscopy and AlphaFold approach offers insights into ligand binding and complement activation.

Pattern recognition molecules (PRMs) form an important part of innate immunity, where they facilitate the response to infections and damage by triggering processes such as inflammation. The pentraxin family of soluble PRMs comprises long and short pentraxins, with the former containing unique N-terminal regions unrelated to other proteins or each other. No complete high-resolution structural information exists about long pentraxins, unlike the short pentraxins, where there is an abundance of both X-ray and cryoelectron microscopy (cryo-EM)-derived structures. This study presents a high-resolution structure of the prototypical long pentraxin, PTX3. Cryo-EM yielded a 2.5-Å map of the C-terminal pentraxin domains that revealed a radically different quaternary structure compared to other pentraxins, comprising a glycosylated D4 symmetrical octameric complex stabilized by an extensive disulfide network. The cryo-EM map indicated α-helices that extended N terminal of the pentraxin domains that were not fully resolved. AlphaFold was used to predict the remaining N-terminal structure of the octameric PTX3 complex, revealing two long tetrameric coiled coils with two hinge regions, which was validated using classification of cryo-EM two-dimensional averages. The resulting hybrid cryo-EM/AlphaFold structure allowed mapping of ligand binding sites, such as C1q and fibroblast growth factor-2, as well as rationalization of previous biochemical data. Given the relevance of PTX3 in conditions ranging from COVID-19 prognosis, cancer progression, and female infertility, this structure could be used to inform the understanding and rational design of therapies for these disorders and processes.

High CRP-albumin ratio predicts poor prognosis in transplant ineligible elderly patients with newly diagnosed acute myeloid leukemia.

Acute myeloid leukemia (AML) patients older than 65 years have a poor prognosis. Recently, CAR (C-reactive-protein/albumin ratio) has been actively reported as a prognostic index reflecting the nutritional and inflammatory status of elderly patients with solid tumors, but the usefulness of this index as a prognostic indicator in transplant-ineligible elderly AML patients has not been investigated. We studied genetic alterations and CARs in 188 newly diagnosed AML patients aged 65 years or older who were treated in a multicenter setting and had treated without HSCT. Both NCCN 2017 risk group, reflecting the genetic component of the tumor, and CAR, reflecting the inflammatory and nutritional status of the patient, successfully stratified the overall survival (OS) of the patients (2-year OS; CAR low vs high, 42.3% vs 17.8%, P < 0.001). Furthermore, in multivariate analysis, NCCN 2017 poor group and high CAR were extracted as independent poor prognostic factors predicting 2-year OS in the current study. We found, for the first time, that CAR at diagnosis predicted the prognosis of elderly patients with newly diagnosed AML treated without HSCT.

Plasma MIA, CRP, and Albumin Predict Cognitive Decline in Parkinson's Disease.

OBJECTIVE: Using a multi-cohort, discovery-replication-validation design, we sought new plasma biomarkers that predict which individuals with Parkinson's disease (PD) will experience cognitive decline. METHODS: In 108 discovery cohort PD individuals and 83 replication cohort PD individuals, we measured 940 plasma proteins on an aptamer-based platform. Using proteins associated with subsequent cognitive decline in both cohorts, we trained a logistic regression model to predict which patients with PD showed fast (> = 1 point drop/year on Montreal Cognitive Assessment [MoCA]) versus slow (< 1 point drop/year on MoCA) cognitive decline in the discovery cohort, testing it in the replication cohort. We developed alternate assays for the top 3 proteins and confirmed their ability to predict cognitive decline - defined by change in MoCA or development of incident mild cognitive impairment (MCI) or dementia - in a validation cohort of 118 individuals with PD. We investigated the top plasma biomarker for causal influence by Mendelian randomization (MR). RESULTS: A model with only 3 proteins (melanoma inhibitory activity protein [MIA], C-reactive protein [CRP], and albumin) separated fast versus slow cognitive decline subgroups with an area under the curve (AUC) of 0.80 in the validation cohort. The individuals with PD in the validation cohort in the top quartile of risk for cognitive decline based on this model were 4.4 times more likely to develop incident MCI or dementia than those in the lowest quartile. Genotypes at MIA single nucleotide polymorphism (SNP) rs2233154 associated with MIA levels and cognitive decline, providing evidence for MIA's causal influence. CONCLUSIONS: An easily obtained plasma-based predictor identifies individuals with PD at risk for cognitive decline. MIA may participate causally in development of cognitive decline. ANN NEUROL 2022;92:255-269.