High Levels Of Acute Phase Reactants Research Articles

The proteomic signature of circulating extracellular vesicles following intracerebral hemorrhage: Novel insights into mechanisms underlying recovery

Circulating extracellular vesicles (EVs) can participate in innate repair processes triggered after intracerebral hemorrhage (ICH). We aimed to describe changes in the proteomic profile of circulating EVs between the acute and subacute phases of ICH and to compare the findings depending on outcomes, as an approach to unraveling such repair mechanisms.This was a prospective observational study including patients with non-traumatic supratentorial ICH. Exclusion criteria were previous disability, signs of herniation on baseline computed tomography, or limited life expectancy. EVs were isolated from blood samples at 24 h and 7 days after symptom onset. After 6-months' follow-up, patients were dichotomized into poor and good outcomes, defining good as an improvement of >10 points or > 50 % on the National Institutes of Health Stroke Scale and a modified Rankin Scale of 0–2. The protein cargo was analyzed by quantitative mass spectrometry and compared according to outcomes.Forty-four patients completed follow-up, 16 (35.5 %) having good outcomes. We identified 1321 proteins in EVs, 37 with differential abundance. In patients with good outcomes, proteins related to stress response (DERA, VNN2, TOMM34) and angiogenesis (RHG01) had increased abundance at 7 days. EVs from patients with poor outcomes showed higher levels of acute-phase reactants (CRP, SAA2) at 7 days compared with 24 h.In conclusion, the protein content of circulating EVs in patients with ICH changes over time, the changes varying depending on the clinical outcome, with greater abundance of proteins potentially involved in the repair processes of patients with good outcomes.

Synovial tissue features associated with poor prognosis in inflammatory arthritis

BackgroundInflammatory arthritis encompasses a group of immune-mediated diseases characterized by chronic joint inflammation. Despite having pathogenic mechanisms in common, the prognosis of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and undifferentiated arthritis (UA) could be different regarding progression to chronic, to erosive, or to self-limited disease. Our aim was to evaluate the potential association of synovial tissue (ST) inflammatory cell infiltrate, the presence of ectopic lymphoid neogenesis (LN +) structures, and poor prognosis factors (PPF) in patients with RA, PsA, and UA.MethodsWe conducted a retrospective study including patients with active arthritis (RA, PsA, UA) who had ST obtained by rheumatological arthroscopy or ultrasound-guided biopsy. Clinical, demographic, and immunohistochemical data of the synovium was evaluated. Patients with biological therapy at the time of synovial biopsy were excluded. PPF in patients with RA and UA were defined by the presence of anti-cyclic citrullinated peptide antibodies and/or rheumatoid factor, development of bone erosions, or requirement of biological therapy during the follow-up. PPF in patients with PsA were defined as the presence of high levels of acute-phase reactants (ESR/CRP), dactylitis or nail involvement at the time of biopsy, development of bone erosion, or requirement of biological therapy during the follow-up.ResultsA total of 88 patients were included: 26 RA, 33 PsA, and 29 UA. All patients were followed up for 5 years after the biopsy. Fourteen (53.84%) RA patients had PPF, and 17 (65.38%) had LN + . LN + was associated with PPF (p 0.038) and biologic therapy initiation (p 0.018). A total of 14 (43.75%) PsA patients had PPF. CD15 infiltrate (410.68 [SD 477.63] cells/mm2) was associated with PPF (p 0.008) in PsA patients. Sixteen (55.17%) patients with UA had PPF, and 13 (44.82%) had LN + . In this group, synovial CD68 + macrophages cells density was negatively correlated with DAS28-CRP (r = − 0.346, p 0.042).ConclusionsThe presence of LN + and higher CD15 + polymorphonuclear cells infiltrate was associated with PPF in RA and PsA, respectively. No associations were found for UA. These findings suggest a great heterogeneity of the ST features and its pathogenic implications in the subtypes of inflammatory arthritis.

Ankilozan Spondilitli Hastalarda Akut Faz Reaktanlarının Değerlendirilmesi

Objective: To determine the high levels of acute phase reactants (APR) of ankylosing spondylitis (AS) patients at diagnosis and follow-up, and to investigate the relationship between patients’ high levels of APR and patients’ disease activity levels and clinical characteristics.
 Material and Methods : 948 patients who were diagnosed with AS according to the modified 1984 New York criteria and followed-up at the university rheumatology clinic were included in this study. The patients’ erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels across all visits were retrospectively reviewed through the registry and the hospital’s database.
 Results: At first visit, high levels of CRP and ESR were observed in 626 (68.5%) and 578 (64.6%) patients respectively. During follow-up 84.6% of patients had high CRP and 69.5% patients had high ESR, however in 10% of patients APRs did not increase at all. There was good correlation between ESR and CRP (r=0.666, p=0.000). A better correlation was observed at first visit between CRP and BASDAI (r=0.81, p=0.23) or ASDAS (r=0.468, p=0.000) compared to ESR and BASDAI (r=0.111, p=0.02) or ASDAS (r=0.334, p=0.000). Compared to BASDAI, ASDAS with either ESR (p=0.00) or CRP (very high disease activity-p=0.000, inactive disease-p=0.001) had better performance in evaluating the activity of the patient in inactive and very high levels of severe disease.
 Conclusions: Our results showed, high levels of acute phase reactants is not rare in AS patients. APR should be considered the most significant laboratory diagnostics in the evaluation of AS and/or response to the treatment.

Patterns of myocardial involvement in children during COVID-19 pandemic: Early experience from northern Italy.

There is limited information about coronavirus disease 2019 (COVID-19) in the pediatric population. Preliminary data suggest a not insignificant prevalence of cardiac involvement. Here, we report our early experience with COVID-19 in the pediatric population. These patients display exceptionally high levels of acute-phase reactants. The clinical syndrome in these patients is somewhat similar to Kawasaki disease with or without myocardial involvement. In some cases, the presentation mimics typical myocarditis. Severe myocardial involvement is associated with transient electrocardiographic and echocardiographic abnormalities. These findings may be due to the cardiotropic nature of the virus or may be the result of an immunologic response to the infection.

Amyloid A Amyloidosis After Renal Transplantation: An Important Cause of Mortality.

There are limited data on the outcome of transplant recipients with familial Mediterranean fever (FMF)-associated AA amyloidosis. The aim of the present study is to evaluate demographic, clinical, laboratory, and prognostic characteristics and outcome measures of these patients. Eighty-one renal transplant recipients with FMF-associated AA amyloidosis (group 1) and propensity score-matched transplant recipients (group 2, n = 81) with nonamyloidosis etiologies were evaluated in this retrospective, multicenter study. Recurrence of AA amyloidosis was diagnosed in 21 patients (group 1a), and their features were compared with 21 propensity score-matched recipients with FMF amyloidosis with no laboratory signs of recurrence (group 1b). The risk of overall allograft loss was higher in group 1 compared with group 2 (25 [30.9%] versus 12 [14.8%]; P = 0.015 [hazard ratio, 2.083; 95% confidence interval, 1.126-3.856]). Patients in group 1 were characterized by an increased risk of mortality compared with group 2 (11 [13.6%] versus 0%; P = 0.001 [hazard ratio, 1.136; 95% confidence interval, 1.058-1.207]). Kaplan-Meier analysis revealed that 5- and 10-year patient survival rates in group 1 (92.5% and 70.4%) were significantly lower than in group 2 (100% and 100%; P = 0.026 and P = 0.023, respectively). Although not reaching significance, overall, 5- and 10-year graft survival rates (57.1%, 94.7%, and 53.8%, respectively) in group 1a were worse than in group 1b (76.2%, 95%, and 77.8%, respectively; P = 0.19, P = 0.95, and P = 0.27, respectively). AA amyloidosis is associated with higher risk of mortality after kidney transplantation. Inflammatory indicators should be monitored closely, and persistent high levels of acute-phase reactants should raise concerns about amyloid recurrence in allograft.

A clinical guide to autoinflammatory diseases: familial Mediterranean fever and next-of-kin

Autoinflammatory diseases are associated with abnormal activation of the innate immune system, leading to clinical inflammation and high levels of acute-phase reactants. The first group to be identified was the periodic fever diseases, of which familial Mediterranean fever (FMF) is the most common. In FMF, genetic results are not always straightforward; thus, flowcharts to guide the physician in requesting mutation analyses and interpreting the findings are presented in this Review. The other periodic fever diseases, which include cryopyrin-associated periodic syndromes (CAPS), TNF receptor-associated periodic syndrome (TRAPS) and mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS), have distinguishing features that should be sought for carefully during diagnosis. Among this group of diseases, increasing evidence exists for the efficacy of anti-IL-1 treatment, suggesting a major role of IL-1 in their pathogenesis. In the past decade, we have started to learn about the other rare autoinflammatory diseases in which fever is less pronounced. Among them are diseases manifesting with pyogenic lesions of the skin and bone; diseases associated with granulomatous lesions; diseases associated with psoriasis; and diseases associated with defects in the immunoproteasome. A better understanding of the pathogenesis of these autoinflammatory diseases has enabled us to provide targeted biologic treatment at least for some of these conditions.

Interaction between interleukin-6 and the natural anticoagulant system in acute stroke.

Inflammatory reactions mediated by cytokines are involved in the pathogenesis of acute stroke. Decrease in circulating levels of protein C (PC) and protein S (PS) induced by inflammatory cytokines has been postulated as a potential mechanism for a procoagulant tendency during acute stroke. The procoagulant state associated with impairments in natural anticoagulants may induce microvascular obstruction leading to a tissue perfusion reduction that worsens cerebral ischemia. Interleukin-6 (IL-6) regulate the synthesis of C4b-binding protein (C4BP), an acute-phase protein that also regulates PS plasma levels. We measured IL-6, C4BP, erythrocyte sedimentation rate (ESR), total and free PS and PC in 44 patients with acute ischemic stroke to determine if IL-6 decreases circulating levels of natural anticoagulants through the C4BP pathway and if these acute changes in natural anticoagulants may have clinical implications. Patients with higher levels of IL-6 had more severe neurologic deficits on admission, greater infarct size, higher levels of acute-phase reactants, and lower levels of free PS. IL-6 was significantly correlated with C4BP, ESR, and free PS levels. PC levels were also lower in the group of patients with greater IL-6, but differences were not statistically significant. No correlations were found between C4BP and natural anticoagulants. Severe neurologic deficit, greater infarct volume, atrial fibrillation, increased levels of inflammatory parameters (ESR and IL-6), and reduced levels of free PS were associated with disabling stroke at 3 months, but only neurologic severity and ESR remained as independent predictors of stroke disability on multiple regression analysis. Inflammatory reactions mediated by IL-6 during the acute phase of stroke influence the modulation of free PS. However, variations in free PS levels do not have implications for clinical outcome in stroke patients. The link between proinflammatory cytokines and free PS in the acute phase of stroke is not related to the C4BP pathway.