General Marker Of Inflammation Research Articles

Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential biomarkers in Behçet's disease: ameta-analysis.

The mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have attracted interest as possible indicators of inflammation and disease activity in various diseases. This meta-analysis assessed the association between NLR, MPV, PLR, and Behçet's disease (BD) and their correlation with disease activity and thrombosis. Athorough search of the Medline, Embase, and Cochrane databases was performed to identify relevant studies. Studies comparing NLR, MPV, and PLR between patients with BD and healthy controls, as well as studies examining these measures in connection with disease activity and thrombosis in BD satisfied the inclusion criteria. The standardized mean difference (SMD) and 95% confidence interval (CI) were used to calculate the effect sizes. This meta-analysis included 24articles. The findings revealed no discernible differences in MPV between the BD and control groups (p = 0.992). NLR was substantially higher in the BD group than in the control group (p < 0.001). PLR was higher in the BD group than in the control group (p = 0.030), indicating that BD is associated with alarger PLR. Patients with active and inactive BD did not vary significantly in terms of disease activity according to the MPV. Comparing MPV between patients with BD with and without thrombosis showed no discernible changes. However, individuals with active BD had aconsiderably higher NLR and PLR than those with inactive BD (p = 0.003 and p = 0.005, respectively). The statistical significance threshold for the association between NLR, PLR, and thrombosis in patients with BD was not met. NLR and PLR can be regarded as general markers of inflammation according to the results of this meta-analysis.

Immune marker reductions in black and white Americans following sleeve gastrectomy in the short-term phase of surgical weight loss.

Surgical weight loss procedures like vertical sleeve gastrectomy (SG) are sufficient in resolving obesity comorbidities and are touted to reduce the burden of pro-inflammatory cytokines and augment the release of anti-inflammatory cytokines. Recent reports suggest a reduced improvement in weight resolution after SG in Black Americans (BA) versus White Americans (WA). The goal of this study was to determine if differences in immunoglobulin levels and general markers of inflammation after SG in Black Americans (BA) and White Americans (WA) may contribute to this differential resolution. Personal information, anthropometric data, and plasma samples were collected from 58 participants (24 BA and 34 WA) before and 6 weeks after SG for the measurement of immunoglobulin A (IgA), IgG, IgM, C-reactive protein (CRP), and transforming growth factor (TGFβ). Logistic regression analysis was used to determine the relationship of measures of body size and weight and inflammatory markers. Both IgG and CRP were significantly elevated in BA in comparison to WA prior to weight loss. Collectively, IgG, TGFβ, and CRP were all significantly reduced at six weeks following SG. CRP levels in BA were reduced to a similar extent as WA, but IgG levels were more dramatically reduced in BA than WA despite the overall higher starting concentration. No change was observed in IgA and IgM. These data suggest that SG improves markers of immune function in both BA and WA. More diverse markers of immune health should be studied in future work.

Occupational quartz and particle exposure affect systemic levels of inflammatory markers related to inflammasome activation and cardiovascular disease

BackgroundThe inflammatory responses are central components of diseases associated with particulate matter (PM) exposure, including systemic diseases such as cardiovascular diseases (CVDs). The aim of this study was to determine if exposure to PM, including respirable dust or quartz in the iron foundry environment mediates systemic inflammatory responses, focusing on the NLRP3 inflammasome and novel or established inflammatory markers of CVDs.MethodsThe exposure to PM, including respirable dust, metals and quartz were determined in 40 foundry workers at two separate occasions per worker. In addition, blood samples were collected both pre-shift and post-shift and quantified for inflammatory markers. The respirable dust and quartz exposures were correlated to levels of inflammatory markers in blood using Pearson, Kendall τ and mixed model statistics. Analyzed inflammatory markers included: 1) general markers of inflammation, including interleukins, chemokines, acute phase proteins, and white blood cell counts, 2) novel or established inflammatory markers of CVD, such as growth/differentiation factor-15 (GDF-15), CD40 ligand, soluble suppressor of tumorigenesis 2 (sST2), intercellular/vascular adhesion molecule-1 (ICAM-1, VCAM-1), and myeloperoxidase (MPO), and 3) NLRP3 inflammasome-related markers, including interleukin (IL)-1β, IL-18, IL-1 receptor antagonist (IL-1Ra), and caspase-1 activity.ResultsThe average respirator adjusted exposure level to respirable dust and quartz for the 40 foundry workers included in the study was 0.65 and 0.020 mg/m3, respectively. Respirable quartz exposure correlated with several NLRP3 inflammasome-related markers, including plasma levels of IL-1β and IL-18, and several caspase-1 activity measures in monocytes, demonstrating a reverse relationship. Respirable dust exposure mainly correlated with non-inflammasome related markers like CXCL8 and sST2.ConclusionsThe finding that NLRP3 inflammasome-related markers correlated with PM and quartz exposure suggest that this potent inflammatory cellular mechanism indeed is affected even at current exposure levels in Swedish iron foundries. The results highlight concerns regarding the safety of current exposure limits to respirable dust and quartz, and encourage continuous efforts to reduce exposure in dust and quartz exposed industries.

Predictive model for BNT162b2 vaccine response in cancer patients based on blood cytokines and growth factors.

Patients with cancer, especially hematological cancer, are at increased risk for breakthrough COVID-19 infection. So far, a predictive biomarker that can assess compromised vaccine-induced anti-SARS-CoV-2 immunity in cancer patients has not been proposed. We employed machine learning approaches to identify a biomarker signature based on blood cytokines, chemokines, and immune- and non-immune-related growth factors linked to vaccine immunogenicity in 199 cancer patients receiving the BNT162b2 vaccine. C-reactive protein (general marker of inflammation), interleukin (IL)-15 (a pro-inflammatory cytokine), IL-18 (interferon-gamma inducing factor), and placental growth factor (an angiogenic cytokine) correctly classified patients with a diminished vaccine response assessed at day 49 with >80% accuracy. Amongst these, CRP showed the highest predictive value for poor response to vaccine administration. Importantly, this unique signature of vaccine response was present at different studied timepoints both before and after vaccination and was not majorly affected by different anti-cancer treatments. We propose a blood-based signature of cytokines and growth factors that can be employed in identifying cancer patients at persistent high risk of COVID-19 despite vaccination with BNT162b2. Our data also suggest that such a signature may reflect the inherent immunological constitution of some cancer patients who are refractive to immunotherapy.

Identifying biomarkers of ventilator induced lung injury during one-lung ventilation surgery: a scoping review.

Ventilator-induced lung injury (VILI) can occur as a result of mechanical ventilation to two lungs. Thoracic surgery often requires one-lung ventilation (OLV). The potential for VILI is likely higher in OLV. The impact of OLV on development of post-operative pulmonary complications is not well understood. We aimed to perform a scoping review to determine reliable biomarkers of VILI after OLV. A scoping review was performed using Cochrane Collaboration methodology. We searched Medline, EMBASE and SCOPUS. Gray literature was searched. Studies of adult human or animal models without pre-existing lung damage exposed to OLV, with biomarker responses analyzed were included. After screening 5,613 eligible papers, 89 papers were chosen for full text review, with 29 meeting inclusion. Approximately half (52%, n=15) of studies were conducted in humans in an intra-operative setting. Bronchoalveolar lavage (BAL) & serum analyses with enzyme-linked immunosorbent assay (ELISA)-based assays were most commonly used. The majority of analytes were investigated by a single study. Of the analytes that were investigated by two or more studies (n=31), only 16 were concordant in their findings. Across all sample types and studies 84% (n=66) of the 79 inflammatory markers and 75% (n=6) of the 8 anti-inflammatory markers tested were found to increase. Half (48%) of all studies showed an increase in TNF-α or IL-6. A scoping review of the state of the evidence demonstrated that candidate biomarkers with the most evidence and greatest reliability are general markers of inflammation, such as IL-6 and TNF-α assessed using ELISA assays. Studies were limited in the number of biomarkers measured concurrently, sample size, and studies using human participants. In conclusion these identified markers can potentially serve as outcome measures for studies on OLV.

C-Reactive Protein Is a Poor Marker of Baseline Inflammation in Prostate Cancer and Response to Radiotherapy or Androgen Ablation.

IntroductionC-reactive protein (CRP) is an acute-phase reactant used as a general marker for inflammation. Isolated levels have been associated with prostate cancer development, prostate-specific antigen (PSA), Gleason score, and treatment response. We seek to establish whether CRP levels reflect inflammation caused by prostate cancer by comparing levels at various points of time before, during, and after therapy.Materials and methodsA total of 209 patients had a complete blood count (CBC), PSA, and CRP taken at up to four different time points. Labs were performed up to one week prior to androgen ablation via leuprolide injection (pre-AA), up to one week prior to radiotherapy (RT) (pre-RT), within one week of RT completion (post-RT), and three months following RT completion (FU [follow-up]).ResultsSignificant relationships were found between CRP and WBC pre-AA (p-value=0.0050), pre-RT (p-value=0.0170), and post-RT (p-value=0.0113), but not at FU (p=.096). CRP had no significant relationship with PSA or lymphocytes at any time points. PSA was significantly affected by androgen ablation but lymphocytes, WBCs, and CRP were not. No CRP levels were associated with risk groups or FU-PSA. Lymphatic radiation fields significantly decreased WBCs and lymphocytes but not CRP.PSA, WBC, and lymphocytes all significantly decreased from pre-RT to post-RT, followed by a significant recovery. CRP did not significantly change during any of these periods and was not significantly related to changes in PSA, WBCs, or lymphocytes.ConclusionCRP is not a sensitive marker of the acute inflammatory effects of non-metastatic prostate cancer and treatment response with androgen ablation or radiation therapy.

The majority of SARS-CoV-2-specific antibodies in COVID-19 patients with obesity are autoimmune and not neutralizing

Background/objectivesObesity decreases the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. How obesity impacts the quality of the antibodies secreted, however, is not understood. Therefore, the objective of this study is to evaluate the presence of neutralizing versus autoimmune antibodies in COVID-19 patients with obesity.Subjects/methodsThirty serum samples from individuals who tested positive for SARS-CoV-2 infection by RT-PCR were collected from inpatient and outpatient settings. Of these, 15 were lean (BMI < 25) and 15 were obese (BMI ≥ 30). Control serum samples were from 30 uninfected individuals, age-, gender-, and BMI-matched, recruited before the current pandemic. Neutralizing and autoimmune antibodies were measured by ELISA. IgG autoimmune antibodies were specific for malondialdehyde (MDA), a marker of oxidative stress and lipid peroxidation, and for adipocyte-derived protein antigens (AD), markers of virus-induced cell death in the obese adipose tissue.ResultsSARS-CoV-2 infection induces neutralizing antibodies in all lean but only in few obese COVID-19 patients. SARS-CoV-2 infection also induces anti-MDA and anti-AD autoimmune antibodies more in lean than in obese patients as compared to uninfected controls. Serum levels of these autoimmune antibodies, however, are always higher in obese versus lean COVID-19 patients. Moreover, because the autoimmune antibodies found in serum samples of COVID-19 patients have been correlated with serum levels of C-reactive protein (CRP), a general marker of inflammation, we also evaluated the association of anti-MDA and anti-AD antibodies with serum CRP and found a positive association between CRP and autoimmune antibodies.ConclusionsOur results highlight the importance of evaluating the quality of the antibody response in COVID-19 patients with obesity, particularly the presence of autoimmune antibodies, and identify biomarkers of self-tolerance breakdown. This is crucial to protect this vulnerable population at higher risk of responding poorly to infection with SARS-CoV-2 than lean controls.

Serum inflammatory profiles in cystic fibrosis mice with and without Bordetella pseudohinzii infection

Cystic fibrosis (CF) is an autosomal recessive disease caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein, and is marked by an accumulation of mucus in affected airways resulting in persistent infection and chronic inflammation. Quantitative differences in inflammatory markers have been observed in CF patient serum, tracheal cells, and bronchoalveolar lavage fluid, in the absence of detectable infection, implying that absent CFTR function alone may result in dysregulated immune responses. To examine the relationship between absent CFTR and systemic inflammation, 22 analytes were measured in CF mice (F508del/F508del) sera using the MSD multiplex platform. Pro-inflammatory cytokines IL-2, TNF-α, IL-17α, IFN-γ, IL-1β, and MIP-3α are significantly elevated in infection-naïve CF mice (p < 0.050). Anti-inflammatory cytokines IL-10 and IL-4 are also significantly increased (p = 0.00003, p = 0.004). Additionally, six general markers of inflammation are significantly different from non-CF controls (p < 0.050). To elucidate the effects of chronic infection on the CF inflammatory profile, we examined CF mice exposed to spontaneous Bordetella pseudohinzii infections. There are no statistical differences in nearly all inflammatory markers when compared to their infection-naïve CF counterparts, except in the Th2-derived IL-4 and IL-5 which demonstrate significant decreases following exposure (p = 0.046, p = 0.045). Lastly, following acute infection, CF mice demonstrate elevations in nearly all inflammatory markers, but exhibit a shortened return to uninfected levels over time, and suppression of Th1-derived IL-2 and IL-5 (p = 0.043, p = 0.011). These results imply that CF mice have a persistent inflammatory profile often indistinguishable from chronic infection, and a dysregulated humoral response during and following active infection.

Interrelationship of Seasons With Inflammation, Foods, Cardio-Metabolic Health, and Smoking Status Among Breast Cancer Survivors

Abstract Objectives Seasons can affect human inflammatory status and the occurrence of diseases, and foods may also have differential impacts on inflammation across seasons; however, few studies have investigated whether there are independent and joint impacts of seasons and red meat, fruit and vegetable intakes on inflammation in breast cancer survivors. Methods We conducted a cross-sectional study by leveraging a large cohort, the Women's Healthy Eating and Living (WHEL) study. The WHEL study comprised primarily early stage breast cancer survivors and collected blood samples, dietary intake, demographic, and health status information at baseline. We selected 2919 participants who provided baseline dietary information and had measurement of C-reactive protein (CRP), a general marker of inflammation. Results In our multivariable-adjusted analyses, we found that red meat intakes were positively associated, while fruit and vegetable intakes were inversely associated with CRP; blood collected in the winter season was associated with lower CRP when compared to summer; and increased smoking intensity and body mass index (BMI) as well as having cardio-metabolic conditions (such as heart disease or diabetes) were positively associated with CRP. Furthermore, we examined the joint associations of food intakes and the season of blood draw with CRP in different subgroups. We found that moderate intakes of red meat were associated with a reduction of CRP in winter but not in other seasons; increased intakes of fruit and vegetables were associated with reduced inflammation in most seasons except winter. These associations were observed in most subgroups except past smokers with pack-years 15, in whom we observed no benefit of red meat intakes in winter. Conclusions Our study provides valuable evidence for considering seasonal impacts on inflammation and seasonal food impacts in different subgroups among breast cancer survivors. The results of our study are in line with one of the emphases of the current NIH 2020–2030 nutrition strategy plan—namely, pay attention to what, when, and who should eat. Funding Sources TRDRP.

MO902SERUM FREE LIGHT CHAINS IN HEMODIALYSIS PATIENTS: A BRIDGE BETWEEN INFLAMMATION, IMMUNE SYSTEM DYSFUNCTION AND MORTALITY RISK

Abstract Background and Aims Uremic toxins, poor removed by conventional hemodialysis (HD), represent independent risk factors for mortality in end-stage renal disease (ESRD). Middle uremic toxin molecules were associated to pathological features of uremia, such as immune dysfunction and inflammation. These two entities are not mutually exclusive, but they could represent two sides of the same coin. ESRD-associated inflammation is closely related to the activation of innate immune system. Free light chain (FLC) may be a specific assessment of inflammation, representing a direct function of adaptive immunity through B-cell lineage production rather than a general marker of inflammation. While several studies have assessed the relation between FLCs and mortality risk in chronic kidney disease (CKD), FLCs, as uremic toxins in non-multiple myeloma dialyzed patients, were marginally analyzed. The aim of this prospective study was to evaluate the clinical impact of FLCs levels in HD patients, during a 2-years follow-up analysing the relations with biomarkers of inflammation, such as C-reactive protein (CRP) and procalcitonin (PCT), main lymphocytes subsets, such as CD4+ and CD8+ T cell count and high mobility group box (HMGB) -1 levels, as expression of the innate immune system. The potential link between FLCs levels and mortality risk was assessed. Method 190 patients on chronic hemodialysis at the Nephrology and Dialysis Unit of Papardo Hospital in Messina, Italy, were enrolled and followed for 2 years. Inclusion criteria were: age &amp;gt;18 years, absence or &amp;lt;200 ml/die residual diuresis, κ/λ ratio within the renal reference range (0.37–3.1). Receiver operating characteristics (ROC) analysis was performed to estimate the cut-off points of HMGB-1 and cFLC. Kaplan-Meier survival analysis and Cox proportional multivariate hazards model were used for clinical outcome. Results HD patients were characterized by high FLC levels. κFLC values were 182.3 (IQR: 140.2 – 216.1) mg/L, whereas λFLC levels were 108.2 (IQR: 72.7 – 143.2) mg/L. The median combined (c) FLC concentration was 182.9 mg/L (IQR = 207.8 – 330.2), which was extremely greater than the median reported in the general population (normal range = 9.3 – 43.3 mg/L) and in CKD patients [68.9 mg/L (IQR = 49.4 – 100.9)]. No differences in cFLC levels were revealed according to dialysis techniques. HD patients showed significant reduction of CD4+ and CD4+/CD8+ ratio. High HMGB1 levels were detected in HD patients (161.3 ± 39.7 ng/ml) and positively related to PCT and cFLC (r = - 0.38; p &amp;lt; 0.001), with an inverse relation to CD4+/CD8+ ratio. cFLC positively correlated with β2 microglobulin, hemoglobin, and HMGB1. Conversely, an inverse correlation was revealed with surrogate markers of inflammation, such as CRP, procalcitonin, neutrophil counts. There were 49 deaths during the follow-up. The majority (23/49) of deaths were attributed to cardiovascular disease, the remainder to infection and malignancy. cFLCs and sHMGB-1 levels in this group were significantly elevated. By ROC analysis, HMGB-1 levels &amp;gt; 100.9 ng/mL and cFLC &amp;gt; 223.4 mg/l were associated with a significantly lower survival rate (p &amp;lt; 0.02 by log-rank test) than for patients with lower levels when using Kaplan-Meier analysis. After adjusting for confounding factors, by Cox proportional hazards method, the difference remained statistically significant (p = 0.02) Conclusion Our study demonstrated an independent relation between high cFLC levels and mortality in HD patients. cFLCs represent a potential biomarker of “inflammunity”, a physiopathological process playing a pivotal role in ESRD, based on a vicious circle between inflammation and immune dysfunction. Further in-depth examinations should be verify our findings, determining whether therapeutic measures targeting cFLC balance, such as hemodiafiltration and expanded dialysis, would be helpful to reduce the “inflammunity” process, characterizing dialyzed patients.

Interrelationship of Seasons with Inflammation, Red Meat, Fruit, and Vegetable Intakes, Cardio-Metabolic Health, and Smoking Status among Breast Cancer Survivors.

Seasons can affect human inflammatory status and the occurrence of diseases, and foods may also have differential impacts on inflammation across seasons; however, few studies have investigated whether there are independent and joint impacts of seasons and red meat, fruit and vegetable intakes on inflammation in breast cancer survivors. We conducted a cross-sectional study by leveraging a large cohort, the Women’s Healthy Eating and Living (WHEL) study. The WHEL study comprised primarily early stage breast cancer survivors and collected blood samples, dietary intake, demographic, and health status information at baseline. We selected 2919 participants who provided baseline dietary information and had measurement of C-reactive protein (CRP), a general marker of inflammation. In our multivariable-adjusted analyses, we found that red meat intakes were positively associated, while fruit and vegetable intakes were inversely associated with CRP; blood collected in the winter season was associated with lower CRP when compared to summer; and increased smoking intensity and body mass index (BMI) as well as having cardio-metabolic conditions (such as heart disease or diabetes) were positively associated with CRP. Furthermore, we examined the joint associations of food intakes and the season of blood draw with CRP in different subgroups. We found that moderate intakes of red meat were associated with a reduction of CRP in winter but not in other seasons; increased intakes of fruit and vegetables were associated with reduced inflammation in most seasons except winter. These associations were observed in most subgroups except past smokers with pack-years ≥ 15, in whom we observed no benefit of red meat intakes in winter. Our study provides valuable evidence for considering seasonal impacts on inflammation and seasonal food impacts in different subgroups among breast cancer survivors. The results of our study are in line with one of the emphases of the current NIH 2020–2030 nutrition strategy plan—namely, pay attention to what, when, and who should eat.

C-Reactive Protein is a Poor Marker of Baseline Inflammation in Prostate Cancer and Response to Radiotherapy or Androgen Ablation

C-Reactive Protein (CRP) is an acute phase reactant used as a general marker for inflammation. There is some evidence that elevated levels are associated with increased risk of prostate cancer development, PSA, Gleason score, and decreased response to chemotherapy and radiotherapy (RT). Available literature largely focuses on pre-therapeutic levels as a prognostic marker. We seek to establish whether CRP levels reflect inflammation caused by prostate cancer before and in response to RT with or without prior androgen ablation (AA). This study included 209 patients who had a CBC, PSA, and CRP taken at up to four different time points. Labs were performed prior to AA via leuprolide injection (pre-AA), up to one week prior to RT (pre-RT), during the final week of RT (post-RT), and 3 months following RT completion (FU). Prior to RT, 33% of patients had received prior prostatectomy and 50.7% had received AA. Radiation fields included pelvic lymph nodes in 82% of patients. For comparisons at each time point, CRP had a significant relationship with WBCs pre-AA (p-value = 0.0050), pre-RT (p-value = 0.0170), and post-RT (p-value = 0.0113), but not at FU (p = .096). CRP had no significant relationship with PSA at any time points. For those who did or did not receive AA, pre-RT mean PSA was significantly lower (2.3 vs 5.4, p-value = 0.0072) while CRP was not. Pre-AA, pre-RT, and post-RT CRP levels were not significantly related to FU-PSA. No CRP levels were associated with risk groups. Only PSA significantly changed from pre-AA to pre-RT (p-value<0.0001). PSA, WBCs, and lymphocytes significantly decreased from pre-RT to post-RT, with significant recovery from post-RT to FU (p-value<0.0001 for all six comparisons), though still with overall significant change from pre-RT to FU (p-value = 0.0054, p-value<0.0001, p-value<0.0001, respectively). CRP did not significantly change during any period, nor significantly relate to changes in WBCs or PSA. There was a significant difference between the treated vs. untreated lymph node groups in post-RT lymphocytes (p-value<0.0001), FU-lymphocytes (p-value<0.0001), post-RT-WBCs (p-value = 0.0004), and FU-WBCs (p-value = 0.0141). CRP was not significantly different between these groups. Our results demonstrate a lack of clinical utility for CRP as a marker of the inflammatory effects of prostate cancer. It has no correlation with PSA levels or trends, before or after radiation therapy, with or without androgen ablation. It does not change with significant PSA decrease after androgen ablation and corresponding decrease in cancer activity. It does not change at the end of radiation therapy despite significant changes in lymphocytes and WBCs. It does not change with 3-month follow-up to correspond with either significant recovery of lymphocytes and WBCs or a decrease of radiation-induced inflammation.

Dissecting the Association Between Inflammation, Metabolic Dysregulation, and Specific Depressive Symptoms

Observational studies highlight associations of C-reactive protein (CRP), a general marker of inflammation, and interleukin 6 (IL-6), a cytokine-stimulating CRP production, with individual depressive symptoms. However, it is unclear whether inflammatory activity is associated with individual depressive symptoms and to what extent metabolic dysregulation underlies the reported associations. To explore the genetic overlap and associations between inflammatory activity, metabolic dysregulation, and individual depressive symptoms. Genome-wide association study (GWAS) summary data of European individuals, including the following: CRP levels (204 402 individuals); 9 individual depressive symptoms (3 of which did not differentiate between underlying diametrically opposite symptoms [eg, insomnia and hypersomnia]) as measured with the Patient Health Questionnaire 9 (up to 117 907 individuals); summary statistics for major depression, including and excluding UK Biobank participants, resulting in sample sizes of 500 199 and up to 230 214 individuals, respectively; insomnia (up to 386 533 individuals); body mass index (BMI) (up to 322 154 individuals); and height (up to 253 280 individuals). In this genetic correlation and 2-sample mendelian randomization (MR) study, linkage disequilibrium score (LDSC) regression was applied to infer single-nucleotide variant-based heritability and genetic correlation estimates. Two-sample MR tested potential causal associations of genetic variants associated with CRP levels, IL-6 signaling, and BMI with depressive symptoms. The study dates were November 2019 to April 2020. Based on large GWAS data sources, genetic correlation analyses revealed consistent false discovery rate (FDR)-controlled associations (genetic correlation range, 0.152-0.362; FDR P = .006 to P < .001) between CRP levels and depressive symptoms that were similar in size to genetic correlations of BMI with depressive symptoms. Two-sample MR analyses suggested that genetic upregulation of IL-6 signaling was associated with suicidality (estimate [SE], 0.035 [0.010]; FDR plus Bonferroni correction P = .01), a finding that remained stable across statistical models and sensitivity analyses using alternative instrument selection strategies. Mendelian randomization analyses did not consistently show associations of higher CRP levels or IL-6 signaling with other depressive symptoms, but higher BMI was associated with anhedonia, tiredness, changes in appetite, and feelings of inadequacy. This study reports coheritability between CRP levels and individual depressive symptoms, which may result from the potentially causal association of metabolic dysregulation with anhedonia, tiredness, changes in appetite, and feelings of inadequacy. The study also found that IL-6 signaling is associated with suicidality. These findings may have clinical implications, highlighting the potential of anti-inflammatory approaches, especially IL-6 blockade, as a putative strategy for suicide prevention.

A Pilot Study on the Effects of Nut Consumption on Cardiovascular Biomarkers.

Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in the United States and changes in lifestyle can minimize the likelihood of succumbing to heart disease. Anti-inflammatory agents are commonly used to reduce the chronic inflammatory state behind the pathogenesis of CVD. Multiple studies have been published correlating nut consumption with a reduction in both heart attacks and strokes. The goal of this study is to determine to what extent the consumption of almonds, hazelnuts, and walnuts have on the blood markers associated with cardiac disease and inflammation.Methods: This was a six-week study in which subject’s baseline values act as controls. Fasting blood draws occurred at week 0, week 2, and after four weeks of intervention (week 6). All participants had undesirable lipid profiles and no medications related to heart disease.Results: Total cholesterol (TC): high-density lipoprotein (HDL-C) ratio was lowered a statistically significant amount at the six-week time point (3.89 ± 0.74) compared to both the zero-week (4.93 ± 1.16, p < 0.01) and two-week (4.63 ± 1.20, p < 0.5) timepoints. Low-density lipoprotein (LDL) measurements were lowered a statistically significant amount at the six-week time point (135.6 ± 15.0 mg/dL) compared to the zero-week (159.7 ± 12.3 mg/dL, p < 0.01). Erythrocyte sedimentation rate (ESR) was lowered a statistically significant amount at six-week time point (10.44 ± 5.05 mm/h) compared to the zero-week (14.44 ± 5.12 mm/h, p < 0.01).Conclusions: Blood markers associated with CVD specifically and the general marker for inflammation associated with many chronic diseases can be favorably modified with the consumption of specific nuts as demonstrated by this study.

Inflammatory marker changes following vertical sleeve gastrectomy in Black Americans and White Americans

Obesity is a disease of excess adiposity accompanied by chronic low‐grade inflammation that has diverse negative impacts on various organ systems, including immuno‐hematologic parameters. Surgical weight loss procedures like vertical sleeve gastrectomy (VSG) are sufficient in resolving obesity comorbidities and are touted to reduce the burden of pro‐inflammatory cytokines and augment release of anti‐inflammatory cytokines. Recent published work suggests that resolution of obesity‐related parameters does not occur in Black Americans to the same extent as seen in White Americans following bariatric surgery. This study aims to determine if early changes to immunoglobulins and general markers of inflammation occur similarly after bariatric surgery in a sampling of Black and White American participants. To test this aim, we collected samples from 12 Black American and 12 White American patients before and 6 weeks after VSG. Collectively, Immunoglobulin G (IgG), TGFβ, and C‐reactive protein were all significantly reduced in the cohort following VSG. However, initial and post‐surgery IgG levels were higher in the Black Americans in comparison to White Americans (p &lt; 0.01). No differences were observed with surgery by either race or time for IgA though IgM levels trended to be elevated in White Americans in comparison to Black Americans. Taken in context to previous work, our data suggest there is a disparity between African American and White American immunoglobulin and cytokine production following bariatric surgery. Further research is necessary to investigate the extent of this divergence and additional chronological changes with bariatric surgery.

Inflammation Is Strongly Associated With Cardiorespiratory Fitness, Sex, BMI, and the Metabolic Syndrome in a Self-reported Healthy Population: HUNT3 Fitness Study

ObjectiveTo investigate whether C-reactive protein (CRP, a general marker of inflammation), neopterin (activated macrophages), lactoferrin (activated neutrophils), and endothelial function (flow-mediated vasodilation [FMD]) are associated with cardiorespiratory fitness (peak oxygen uptake [VO2peak]), sex, body mass index (BMI), and the metabolic syndrome (MetSyn) in a healthy adult population. Patients and MethodsThis was a cross-sectional association study based on the population-based HUNT3 Fitness Study performed from May 15, 2007, through June 23, 2008. Seven hundred forty self-reported healthy respondents (327 women) identified as having the MetSyn were age- and sex-matched with 692 controls (307 women) from the same cohort. Associations between the inflammatory biomarkers and VO2peak, FMD, and the MetSyn were analyzed by multivariate linear regression. ResultsThe CRP level was negatively associated with VO2peak (P<.001), positively associated with the MetSyn (with a stronger effect in men) (P<.001) and BMI (with a stronger effect in women) (P<.01), but not with FMD (P=.34). Lactoferrin was positively associated with the MetSyn (P<.001), but neither neopterin nor lactoferrin were associated with VO2peak or FMD. ConclusionThe CRP level was strongly associated with VO2peak and the MetSyn, but not with FMD. The associations among inflammation, VO2peak, and the MetSyn were strongly influenced by sex and BMI. These data support that low cardiorespiratory fitness should be considered an etiologic factor contributing to systemic inflammation and that reducing body weight and improving VO2peak are methods that may positively affect CRP levels.

PentraSorb C-Reactive Protein: Characterization of the Selective C-Reactive Protein Adsorber Resin.

C-reactive protein (CRP) is well known as a general marker of inflammation. It furthermore represents a reliable risk factor for cardiac events and mediates tissue damage in acute myocardial infarction (AMI). It has been demonstrated that selective CRP depletion by extracorporeal apheresis in a porcine AMI model had beneficial effects on the infarcted area and the cardiac output. We therefore developed a novel adsorber for CRP apheresis from human plasma (PentraSorb CRP). It is intended for use in the clinic as therapy for patients suffering from AMI or other acute inflammatory diseases with elevated CRP plasma levels. The PentraSorb resin specifically bound CRP from human blood plasma and almost no other proteins as determined via Sodium dodecyl sulfate polyacrylamide gel electropheresis (SDS-PAGE). The resin further efficiently and selectively depleted CRP from plasma with low as well as high CRP concentrations (10-100 mg/L) at different flow rates, ranging from 17 to 40 mL/min. The resin was regenerable for up to 200 times without losing its CRP binding capacity or affecting biocompatibility. The depletion of CRP from plasma was comparable between the utilized small-scale column (0.5 mL resin) and the PentraSorb CRP adsorber (20 mL resin volume). The established features can therefore be applied to the clinical setting. In summary, PentraSorb CRP provides a novel, specific, and efficient CRP-binding resin that could be used in apheresis therapy for patients suffering from inflammatory diseases such as AMI, stroke, acute pancreatitis, and Crohn's disease.

Abstract B21: C-reactive protein and ovarian cancer risk in the Ovarian Cancer Cohort Consortium

Abstract Background: C-reactive protein (CRP), a general marker of inflammation, has been consistently associated with increased ovarian cancer risk. However, few studies have had the ability to evaluate differences in association by ovarian tumor subtype. Thus, we leveraged previously measured CRP levels in prediagnostic specimens from 6 studies in the Ovarian Cancer Cohort Consortium (OC3). Methods: We pooled data on CRP and ovarian cancer risk among nested case-control studies conducted in CLUEII, EPIC, NHS, NHSII, NYUWHS, and PLCO; invasive ovarian cancer cases were matched to one or two controls on age, menopausal status, hormone therapy (HT) use, and fasting status. Due to variability in CRP distributions across studies in part due to different assays, we regressed CRP levels on study (with EPIC as the reference), adjusting for predictors of CRP, including age, menopause/HT status, fasting status, BMI, aspirin use, and smoking. Levels for each study (except EPIC) were recalibrated based on the beta coefficient for that study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for natural log-transformed CRP (continuous), quartiles (based on control distributions) and clinical cutpoints (&amp;lt;1, 1-&amp;lt;10, ≥10mg/L) using conditional logistic regression, which implicitly accounts for matching factors. We examined associations for all invasive cancer and by histotype (serous [n=740], endometrioid [n=109], mucinous [n=69], clear cell [n=47]). Primary analyses (model 1) adjusted for reproductive risk factors (oral contraceptive use, number of pregnancies, and tubal ligation); model 2 additionally adjusted for known predictors of CRP, including BMI, smoking, and aspirin use, that also may be related to ovarian cancer risk. Results: There was a marginally significant linear association between CRP and total invasive ovarian cancer risk among 1,135 cases and 2,124 controls (p-trend=0.05), which was slightly attenuated when adjusting for BMI, smoking, and aspirin use (p-trend=0.08). The model 1 OR (95% CI) was 1.24 (0.99-1.54) comparing the top to bottom quartile and 1.90 (1.28-2.81) for ≥10 to &amp;lt;1 mg/L. The corresponding OR (95% CI) for model 2 was 1.21 (0.96-1.53) and 1.86 (1.24-2.79), respectively. Results were generally similar across histotypes with the strongest associations comparing CRP levels ≥10 vs. &amp;lt;1mg/L, although no associations reached statistical significance. Interestingly, the impact of adjusting for BMI, smoking, and aspirin differed across subtypes. For example, the OR (95% CI) comparing the top versus bottom quartile for serous tumors increased from 1.25 (0.95-1.65) in model 1 (reproductive factors) to 1.31 (0.97-1.75) in model 2 (reproductive factors and predictors of CRP). Conversely, the association was largely attenuated for endometrioid tumors when adjusting for predictors of CRP (model 1: OR=1.37 [0.72-2.58]; model 2: OR=1.06 [0.52-2.18]). Conclusion: Our results confirm that CRP, particularly very high levels, is positively associated with risk of ovarian cancer. The association for serous tumors appeared to be independent of reproductive exposures and other factors that are associated with CRP and ovarian cancer; however, the relationship observed for endometrioid tumors was largely explained by BMI. Given that fewer risk factors have been identified for serous tumors, our work supports further exploration of inflammation and immunity in the etiology of this histotype. Further analyses will explore associations by other tumor factors (e.g., grade) and participant characteristics (e.g., menopausal status). Citation Format: Britton Trabert, Renee Fortner, Elizabeth Poole, Nicolas Wentzensen, Shelley Tworoger. C-reactive protein and ovarian cancer risk in the Ovarian Cancer Cohort Consortium. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B21.

S87. THE INITIAL CHANGE IN THE SERUM LEVEL OF C-REACTIVE PROTEIN IN ACUTE PSYCHOSIS IS ASSOCIATED WITH COGNITIVE PERFORMANCE IN LATER PHASES

BackgroundInflammatory processes have been implicated in the pathophysiology of schizophrenia and related psychosis and could be particularly relevant to the associated cognitive deficits. The C-reactive protein (CRP) serves as a general marker of inflammation, and inverse relationships between CRP levels and cognitive performance in acute psychosis have been demonstrated. Here we aimed to investigate how the serum level and initial change of CRP in acutely admitted patients with psychosis were correlated with cognitive performance during a 6-months follow-up period.MethodsThe study is part of a pragmatic, randomized trial comparing four different second-generation antipsychotic drugs, and consists of 208 acute phase patients recruited at admittance for psychosis (schizophrenia, schizoaffective disorder, acute and transient psychotic disorder, delusional disorder, drug-induced psychosis, bipolar disorder except for manic psychosis, or major depressive disorder with psychotic features). The present study reports data for all treatment groups collectively, and does not compare treatment groups.Measurements of CRP and cognitive performance were conducted at baseline (T1) and after an average of 4 weeks after inclusion (T2). Cognition was assessed after 3 months (T3) and 6 months (T4) of follow-up.ResultsGlobal cognition improved during the follow-up period of 6 months, especially in the T1–T2 interval. The different cognitive subdomains showed different time-dependent profiles of improvement, with memory and attention improving significantly also in the later phases. Reduction of the CRP level during the initial follow-up interval (T1–T2) was associated with increased overall cognitive performance in the T2–T4 interval, but not in the T1–T2 interval. For the cognitive subdomains, we found an inverse association between change in CRP level and learning (T1–T2 interval), verbal abilities (T2–T4 interval), and attention (T2–T3 interval).DiscussionThe main finding of the present study was that the global cognitive performance continued to improve from the initial phase (baseline to 4 weeks) of acute psychosis to the later phase (4 weeks–6 months), and was predicted by the change in CRP level that was observed during the initial phase (baseline–4 weeks) of the treatment. These findings might indicate a prolonged effect of inflammatory processes on cognition in acute psychosis, stretching beyond the initial phase.There is substantial evidence that inflammatory processes are involved in the cognitive performance in psychosis. CRP levels have been associated with cognitive impairment in patients with schizophrenia.ConclusionsThese findings indicate that initial changes in the serum level of CRP in the acute phase of psychosis may predict cognitive functioning in later phases of the disease.

A Novel Combination of Biomarkers to Herald the Onset of Sepsis Prior to the Manifestation of Symptoms.

ABSTRACTSepsis, which kills over 200,000 patients and costs over $20 billion in the United States alone, presents a constant but preventable challenge in the healthcare system. Among the more challenging problems that it presents is misdiagnosis due to conflation with other inflammatory processes, as its mechanisms are identical to those of other inflammatory states. Unfortunately, current biomarker tests can only assess the severity and mortality risk of each case, whereas no single test exists that can predict sepsis prior to the onset of symptoms for the purpose of pre-emptive care and monitoring. We propose that a single test utilizing three, rather than two, biomarkers that appear most quickly in the blood and are the most specific for sepsis rather than trauma, may improve diagnostic accuracy and lead to lessened patient morbidity and mortality. Such a test would vastly improve patient outcomes and quality of life, prevent complications for sepsis survivors, and prevent hospital readmissions, saving the American healthcare system money. This review summarizes the current use of sepsis biomarkers to prognosticate morbidity and mortality, and rejects the current single-biomarker and even combination biomarker tests as non-specific and inaccurate for current patient needs/pro-inflammatory cytokines, general markers of inflammation, and proteins specific to myeloid cells (and therefore to infection) are discussed. Ultimately, the review suggests a three-biomarker test of procalcitonin (PCT), interleukin-6 (IL-6), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to diagnose sepsis before the onset of symptoms.