Non-inflammatory Disease Research Articles

Mucosal microbiome is predictive of pediatric Crohn's disease across geographic regions in North America.

Background: Patients with Crohn's disease (CD) have an altered intestinal microbiome, which may facilitate novel diagnostic testing. However, accuracy of microbiome classification models across geographic regions may be limited. Therefore, we sought to examine geographic variation in the microbiome of patients with CD from North America and test the performance of a machine learning classification model across geographic regions. Methods: The RISK cohort included 447 pediatric patients with CD and 221 non-inflammatory bowel disease controls from across North America. Terminal ileum, rectal and fecal samples were obtained prior to treatment for microbiome analysis. We divided study sites into 3 geographic regions to examine regional microbiome differences. We trained and tested the performance of a machine learning classification model across these regions. Results: No differences were seen in the mucosal microbiome of patients with CD across regions or in either the fecal or mucosal microbiomes of controls. Machine learning classification algorithms for patients with CD performed well across regions (area under the receiver operating characteristic curve [AUROC] range of 0.85-0.91) with the best results from terminal ileum. Conclusions: This study demonstrated the feasibility of microbiome based diagnostic testing in pediatric patients with CD within North America, independently from regional influences.

Urine neopterin in childhood acute demyelinating diseases: Potential for differential diagnosis

Inflammatory demyelinating diseases of the central nervous system (CNS) in childhood include clinically and radiologically defined diseases such as acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Differentiation between these phenotypes can be difficult and cases not meeting established diagnostic criteria may remain without any specific diagnosis for months. Laboratory markers can assist in the diagnosis and management of these diseases. Previous studies suggest serum kynurenine-tryptophan pathway products and serum neopterin as biomarkers for CNS autoimmune diseases. Because urine is a reliable and repeatable source for analysis of these products with the additional advantage of easy sampling, we measured neopterin concentrations in serum and urine samples, urinary biopterin and serum kynurenine-tryptophan levels in autoimmune demyelinating diseases of CNS: pediatric multiple sclerosis (pMS, n = 27), MOGAD (n = 10), NMOSD (n = 5) patients and a control group consisting of healthy children or children with non-inflammatory diseases (n = 13), total 55 children. Methods were high performance liquid chromatography (HPLC) for neopterin, biopterin and creatinine in urine and kynurenine and tryptophan in serum; ELISA was used for serum neopterin. Comparison for biomarkers between all diagnostic groups showed urinary neopterin values were significantly higher in the pMS group (p = 0.002). The cut-off point determined by ROC analysis indicated urinary neopterin >167.75 µmol/mol creatinine could distinguish the patients from the controls with a sensitivity of 71% and specificity of 90%. The most significant difference was between the pMS and control groups (p = 0.002) while no difference was observed between pMS patients who were in relapse or stable state. Therefore, urinary neopterin appeared as a potential marker that could differentiate pMS from other demyelinating patient groups MOGAD and NMOSD as well as from controls. The fact that pteridine pathway products had not been studied in urine and serum in children with demyelinating disease before highlights the novelty of this study. If further research in larger samples confirm the present results, these molecules might assist the differential diagnosis of pMS from other demyelinating CNS diseases.

Cardiovascular Disease-Associated Skin Conditions.

According to data from the American Heart Association and the World Health Organization, cardiovascular disease (CVD) is the most frequent cause of premature death. Several inflammatory and non-inflammatory skin diseases have been associated with metabolic syndrome and cardiovascular risk (CVR). Here, we classified these conditions into traditionally CVR-associated and those that have been linked to a lesser degree. Psoriasis and hidradenitis suppurativa are commonly associated with CVD, sharing common inflammatory pathways and a higher prevalence of traditional cardiovascular risk factors. Many other diseases could be associated indirectly – with no common pathogenic features with the atheromatous disease – but share a higher prevalence of standard cardiovascular risk and chronic inflammatory state. This review aims to highlight the associated cardiovascular risk that exists for some dermatologic diseases and sensitize cardiologists, dermatologists, and first care providers to implement risk factor control promptly.

SPP1 in infliximab resistant ulcerative colitis and associated colorectal cancer: an analysis of differentially expressed genes.

Infliximab, a tumour necrosis factor-α (TNFα) antagonist, has advanced the management of ulcerative colitis. Although efficacious, considerable percentage of patients are resistant to treatment. Accumulative inflammatory burden in long-term ulcerative colitis patients refractory to therapy increases the risk of developing colorectal cancer (CRC). Our study investigated anti-TNFα-naïve patients with active ulcerative colitis to identify gene biomarkers whose dysregulated expression correlated with resistance to infliximab (IFX) treatment and poor prognosis in CRC. Differentially expressed genes (DEGs) from two studies (GSE73661 and GSE14580) with colonic mucosal samples were retrieved. Noninflammatory bowel disease controls were compared with those with active ulcerative colitis that either responded or were resistant to IFX before treatment. DEGs from ulcerative colitis samples resistant to IFX were used to construct a protein-protein interaction network, and clustering gene modules were identified. Module DEGs that overlapped with ulcerative colitis samples responsive to IFX were analysed, based on topological closeness and radiality. Hub genes were obtained, and their correlation with CRC progression was evaluated. Their expression in CRC tissues and their tumour microenvironment immune status was estimated. Three clusters composed of 582 DEGs from ulcerative colitis samples resistant to IFX were retrieved. Comparative analysis identified 305 overlapping DEGs with ulcerative colitis samples responsive to IFX. Topological analysis revealed a hub gene - SPP1 - whose overexpression in CRC tissues and patients correlated with increased infiltration of immune signatures and poor prognosis. SPP1 may serve as potential gene biomarker and predictor of resistance to IFX therapy in ulcerative colitis and CRC development.

Elevated levels of IL-32 in cerebrospinal fluid of neuro-Behcet disease: Correlation with NLRP3 inflammasome

Interleukin-32 (IL-32) is a pro-inflammatory cytokine that induces other cytokines involved in inflammation, including tumour necrosis factor (TNF)-α, IL-6 and IL-1β. The objective of this study was to evaluate IL-32, NLRP3 inflammasome, IL-1β, IL-6, IL-17A, TNF-a, IL-10 and IL-37 in cerebrospinal fluid (CSF) and paired serum samples of patients with neuro-Behcet disease (NBD) by ELISA, RT-PCR and Western blotting analysis. A receiver operating characteristic (ROC) curve was employed to explore of the predictive value of IL-32 levels. IL-32, IL-1β, IL-6, IL-17 and TNF-α, were highly expressed in CSF of NBD and multiple sclerosis (MS) patients contrasting with their low levels in patients with noninflammatory neurological diseases (NIND) and Headache attributed to BD (HaBD). IL-32 and NLRP3 inflammasome in NBD, correlate significantly with CRP and ESR. IL-32 should be studied further as potential BD biomarker of inflammation in NBD.

Aortic Wall Inflammation in the Pathogenesis, Diagnosis and Treatment of Aortic Aneurysms

The role of inflammation in the development of aortic aneurysms is emerging, along with the potential diagnostic and therapeutical potential of this correlation. Abdominal aorta aneurysms have a strong inflammatory substrate since atherosclerosis, which is undoubtedly linked to inflammation, is also a predisposing factor to their formation. Yet, data have emerged that the development of thoracic aorta aneurysms involves several inflammatory pathways, although they were previously referred to as a non-inflammatory disease. Since aortic aneurysms are mainly asymptomatic during their clinical course until their complications-which may be lethal-serum biomarkers for their early diagnosis are a necessity. Studies highlight that inflammation molecules may have a critical role in that direction. In addition, imaging techniques that trace aortic wall inflammation are developed in order to predict aneurysm growth rates and sites vulnerable of rupture. Several anti-inflammatory agents have been also studied in animal models and clinical trials for the treatment of aortic aneurysms. This review highlights the role of inflammation in pathogenesis, diagnosis and treatment of aortic aneurysms.

NLRP3 in the Cerebrospinal Fluid as a Potential Biomarker for the Diagnosis and Prognosis of Community-Acquired Bacterial Meningitis in Adults.

ObjectiveTo discover the levels of NLR family pyrin domain-containing 3 (NLRP3) in the cerebrospinal fluid (CSF) from adult patients with community-acquired bacterial meningitis (CABM).MethodsWe enrolled 34 patients with CABM, 20 patients with viral meningitis (VM), and 25 patients with non-inflammatory neurological disease. Data on standard clinical parameters, scores, and outcomes were obtained from clinical records, and inflammasome levels in the CSF were measured by an enzyme-linked immunosorbent assay. The area under the receiver operating characteristic curve (AUROC) was used to quantify the diagnostic and prognostic performance of CSF NLRP3 as a biomarker of CABM.ResultsThe levels of NLRP3 were elevated in the CSF of patients with CABM, but levels for ASC, caspase-1, or other inflammasomes did not vary significantly. CSF NLRP3 was positively correlated with clinical severity and with the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte count, albumin quotient (Qalb), and immunoglobulin G quotient (QIgG). Patients with unfavorable outcomes had higher levels of NLRP3 in the CSF, which were correlated with several blood indicators, including NLR, PLR, and lymphocyte and monocyte counts.ConclusionsOur results suggested that the level of CSF NLRP3 could represent the severity of CABM in adults. CSF NLRP3 may be a good biomarker for the diagnosis of CABM and for the discrimination between CABM and VM. It may also be a better biomarker for predicting the prognosis of adult patients with CABM when compared to the NLR or the lymphocyte and monocyte counts.

NON-IMMUNE MEDIATED MUSCULOSKELETAL DISEASE IN CROHN’S DISEASE PATIENTS BEING EVALUATED FOR INFLAMMATORY SPONDYLOARTHRITIS - A PILOT STUDY

BACKGROUNDMusculoskeletal (MSK) disease is the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). The emphasis in the published literature has been on the inflammatory arthritis associated with IBD, spondyloarthritis (SpA). There is a lack of data regarding common, non-inflammatory MSK diseases such as osteoarthritis and fibromyalgia. This distinction is important, as these two conditions have different prognoses, require different clinical approaches and management.OBJECTIVETo evaluate the prevalence of non-inflammatory MSK disease in a cohort of Crohn’s disease (CD) patients.METHODSThis was a cross-sectional study of a validated CD cohort from a single center registry in New York City conducted from 9/2019 - 1/2021. Recruitment was limited due to the COVID-19 Pandemic. Patients were sent a four question MSK survey (Figure 1) addressing peripheral joint and back symptoms. Those who answered positively to any question were considered to have MSK symptoms. All patients underwent one study visit with a rheumatologist that included: 66/68 tender/swollen joint count (TJC/SJC), Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC), Bath Ankylosing Spondylitis Metrology Index (BASMI), American College of Rheumatology fibromyalgia criteria, ESR and CRP. Disease activity was measured via a modified Ankylosing Spondylitis Disease Activity Score (ASDAS), Harvey Bradshaw Index (HBI), and Inflammatory Bowel Disease Questionnaire (IBD-Q).RESULTS26 CD patients participated. Median age was 45.6±17.7 years, 35% were male, median disease duration was 17.7±14.2 years and 73% were on immunomodulatory agents for CD. Median values (range) for the following physical exam and disease features were: TJC 10.8±13.2 (0-68), SJC 0.9±2.2 (0-66), SPARCC 2.8±3.1 (0-16), BASMI 1.5±1.0 (0-10, higher values: more motion limitation) ASDAS 1.5±0.9 (<1.3: inactive disease, >2.1: high disease activity), HBI 6.8±3.5 and IBD-Q 159±36. Median ESR and CRP were 18.9±22.2 mm/hr (normal 0-22) and 0.6±0.5 mg/dL (normal<0.7), respectively. 16/26 (62%) reported MSK symptoms. 7/16 (43.8%) had features of SpA, while 9/16 (56.3%) did not have evidence by history or exam of SpA and were therefore determined to have non-inflammatory MSK disease. 13/26 (50%) met fibromyalgia diagnostic criteria.CONCLUSIONMSK conditions were very common in this pilot cohort. Though features of SpA were present in almost half of patients, non-inflammatory MSK disease was present in the majority of those with MSK symptoms. While both rheumatologists and gastroenterologists need to recognize the importance of SpA, it is additionally essential to understand that the most common MSK disease in IBD may be non-inflammatory, which has distinct implications for management. Future studies should examine the prevalence of these conditions in larger cohorts of IBD patients.

Increased Numbers of Enteric Glial Cells in the Peyer's Patches and Enhanced Intestinal Permeability by Glial Cell Mediators in Patients with Ileal Crohn's Disease.

Enteric glial cells (EGC) are known to regulate gastrointestinal functions; however, their role in Crohn’s disease (CD) is elusive. Microscopic erosions over the ileal Peyer’s patches are early signs of CD. The aim of this work was to assess the localization of EGC in the follicle and interfollicular region of the Peyer’s patches and in the lamina propria and study the effects of EGC mediators on barrier function in CD patients and non-inflammatory bowel disease (non-IBD) controls. EGC markers, glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein β (S100β) were quantified by immunofluorescence and Western blotting. Both markers showed significantly more EGC in the Peyer’s patches and lamina propria of CD patients compared to the non-IBD controls. In CD patients there were significantly more EGC in Peyer’s patches compared to lamina propria, while the opposite pattern was seen in controls. Barrier function studies using Ussing chambers showed increased paracellular permeability by EGC mediators in CD patients, whereas permeability decreased by the mediators in controls. We show the accumulation of EGC in Peyer’s patches of CD patients. Moreover, EGC mediators induced barrier dysfunction in CD patients. Thus, EGC might have harmful impacts on ongoing inflammation and contribute to the pathophysiology of the disease.

NON-IMMUNE MEDIATED MUSCULOSKELETAL DISEASE IN CROHN'S DISEASE PATIENTS BEING EVALUATED FOR INFLAMMATORY SPONDYLOARTHRITIS - A PILOT STUDY

Musculoskeletal (MSK) disease is the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). The emphasis in the published literature has been on the inflammatory arthritis associated with IBD, spondyloarthritis (SpA). There is a lack of data regarding common, non-inflammatory MSK diseases such as osteoarthritis and fibromyalgia. This distinction is important, as these two conditions have different prognoses, require different clinical approaches and management.

Choroidal vascularity index in thyroid eye disease: comparison with controls and application in diagnosing non-inflammatory active disease

ABSTRACT Purpose To report the differences in choroidal vascularity index (CVI) in thyroid eye disease (TED) and normals and its discriminatory value for differentiating various stages of TED. Methods Prospective, cross-sectional, non-interventional imaging study. Ninety-four eyes of 54 patients were included and divided into 5 groups – normal controls (C), inactive TED (I), active TED (A), non-inflammatory active TED (NIA) and systemic hyperthyroid disorder but no TED (SYS). Choroidal images were acquired using the swept-source optical coherence tomography and the choroid was binarized to calculate the CVI. Results Ninety-four eyes were included. Mean age was 44.52 ± 10.02 years (median 46 years, range 19-65 years). Mean IOP was 16.1 ± 3.37 mm Hg (median 16 mm Hg, range 16–24 mm Hg). Mean Spherical equivalent (SE) was -0.08 ± 1.86 diopters (median 0, range -2.5 to +2.25). Intra-rater agreement was 0.84 (p < 0.001). Inter-rater agreement was noted to be 0.85 (p < 0.001) for consistency and 0.77 (p < 0.001) for absolute agreement. CVI in the A group was 70.11 ± 3.38% and in the NIA group was 69.32 ± 3.5%. Both were comparable to each other and significantly higher than the C, I and SYS groups (p < 0.001). Multiple regression showed that the Clinical Activity Score (CAS) had a positive effect and spheroequivalent had a negative effect on the CVI. At CVI of 66.83%, active TED can be diagnosed with sensitivity of 91.67% and specificity of 82.14% . Conclusions CVI is significantly higher in active TED and NIA TED compared to other groups. It has a good value in differentiating the non-inflammatory active TED eyes from the inactive eyes.

Complexity of Secretory Chemokines in Human Intestinal Organoid Cultures Ex Vivo.

Complexity of Secretory Chemokines in Human Intestinal Organoid Cultures Ex Vivo.

A Novel Three-Dimensional Imaging System Based on Polysaccharide Staining for Accurate Histopathological Diagnosis of Inflammatory Bowel Diseases.

Background & AimsTissue-clearing and three-dimensional (3D) imaging techniques aid clinical histopathological evaluation; however, further methodological developments are required before use in clinical practice.MethodsWe sought to develop a novel fluorescence staining method based on the classical periodic acid-Schiff stain. We further attempted to develop a 3D imaging system based on this staining method and evaluated whether the system can be used for quantitative 3D pathological evaluation and deep learning–based automatic diagnosis of inflammatory bowel diseases.ResultsWe successfully developed a novel periodic acid–FAM hydrazide (PAFhy) staining method for 3D imaging when combined with a tissue-clearing technique (PAFhy-3D). This strategy enabled clear and detailed imaging of the 3D architectures of crypts in human colorectal mucosa. PAFhy-3D imaging also revealed abnormal architectural changes in crypts in ulcerative colitis tissues and identified the distributions of neutrophils in cryptitis and crypt abscesses. PAFhy-3D revealed novel pathological findings including spiral staircase-like crypts specific to inflammatory bowel diseases. Quantitative analysis of crypts based on 3D morphologic changes enabled differential diagnosis of ulcerative colitis, Crohn’s disease, and non-inflammatory bowel disease; such discrimination could not be achieved by pathologists. Furthermore, a deep learning–based system using PAFhy-3D images was used to distinguish these diseases The accuracies were excellent (macro-average area under the curve = 0.94; F1 scores = 0.875 for ulcerative colitis, 0.717 for Crohn’s disease, and 0.819 for non-inflammatory bowel disease).ConclusionsPAFhy staining and PAFhy-3D imaging are promising approaches for next-generation experimental and clinical histopathology.

Эмпирическая терапия – первая линия в лечении вульвовагинальных инфекций

Women with signs of urogenital system infections require diagnostic testing for timely and adequate verification of the pathogen and prescription of therapy considering pathogen eradication. However, the identification of specific pathogens in practice takes some time. Therefore, empirical therapy based on a subjective evaluation of the symptoms of vulvovaginal infections and assessment of drug susceptibility of pathogens is common in practical gynecology. At the same time, it is acceptable to use broad-spectrum agents that act on bacteria, fungi, and protozoa and do not contribute to the development of antibiotic resistance. These are topical antimicrobial agents – antiseptics. Objective. To study the efficacy of dequalinium chloride as first-line treatment of patients with signs of vulvovaginal noninflammatory and inflammatory diseases initiated by opportunistic pathogens and aerobic bacteria. Patients and methods. The study included 74 women aged 18 to 45 years (31.4 ± 0.5 years) who were diagnosed with other inflammation of vagina and vulva (N76) or other non-inflammatory disorders of vagina (N89) based on their complaints and examination during an initial visit to a gynecologist. Prior to treatment, laboratory testing of the vaginal microflora by real-time polymerase chain reaction using the test Femoflor was performed, and empirical therapy with dequalinium chloride was applied. Subsequently, the results of laboratory tests before and after treatment were analyzed, as well as the dynamics of clinical manifestations of vulvovaginal infections against the background of therapy with topical antiseptic. Results. The prescription of dequalinium chloride as empirical therapy is effective for both elimination of the clinical manifestations of vulvovaginal infections and for normalization of the qualitative and quantitative composition of the vaginal microbiota at the outpatient appointment. Conclusion. Dequalinium chloride (Fluomisin®) may be recommended to women for correcting disorders of the vaginal microbiocenosis at their initial visit before the results of laboratory tests are obtained. Key words: vulvovaginal infection, normal microbiota, empirical therapy, dequalinium chloride

An autologous colonic organoid-derived monolayer model to study immune: bacterial interactions in Crohn's disease patients.

ObjectivesCrohn's disease (CD) initiation and pathogenesis are believed to involve an environmental trigger in a genetically susceptible person that results in an immune response against commensal gut bacteria, leading to a compromised intestinal epithelial barrier and a cycle of inflammation. However, it has been difficult to study the contribution of all factors together in a physiologically relevant model and in a heterogenous patient population.MethodsWe developed an autologous colonic monolayer model that incorporated the immune response from the same donor and a commensal bacteria, Faecalibacterium prausnitzii. Two‐dimensional monolayers were grown from three‐dimensional organoids generated from intestinal biopsies, and the epithelial integrity of the epithelium was measured using transepithelial electrical resistance. We determined the effect of immune cells alone, bacteria alone and the co‐culture of immune cells and bacteria on integrity.ResultsMonolayers derived from CD donors had impaired epithelial integrity compared to those from non‐inflammatory bowel disease (IBD) donors. This integrity was further impaired by culture with bacteria, but not immune cells, despite a higher frequency of inflammatory phenotype peripheral T cells in CD donors. Variability in epithelial integrity was higher in CD donors than in non‐IBD donors.ConclusionWe have developed a new autologous model to study the complexity of CD, which allows for the comparison of the barrier properties of the colonic epithelium and the ability to study how autologous immune cells directly affect the colonic barrier and whether this is modified by luminal bacteria. This new model allows for the study of individual patients and could inform treatment decisions.

Proteolysis and deficiency of α1-proteinase inhibitor in SARS-CoV-2 infection

The SARS-CoV-2 pandemia had stimulated the numerous publications emergence on the α1-proteinase inhibitor (α1-PI, α1-antitrypsin), primarily when it was found that high mortality in some regions corresponded to the regions with deficient α1-PI alleles. By analogy with the last century's data, when the root cause of the α1-antitrypsin, genetic deficiency leading to the elastase activation in pulmonary emphysema, was proven. It is evident that proteolysis hyperactivation in COVID-19 may be associated with α1-PI impaired functions. The purpose of this review is to systematize scientific data, critical directions for translational studies on the role of α1-PI in SARS-CoV-2-induced proteolysis hyperactivation as a diagnostic marker and a target in therapy. This review describes the proteinase-dependent stages of a viral infection: the reception and virus penetration into the cell, the plasma aldosterone-angiotensin-renin, kinins, blood clotting systems imbalance. The ACE2, TMPRSS, ADAM17, furin, cathepsins, trypsin- and elastase-like serine proteinases role in the virus tropism, proteolytic cascades activation in blood, and the COVID-19-dependent complications is presented. The analysis of scientific reports on the α1-PI implementation in the SARS-CoV-2-induced inflammation, the links with the infection severity, and comorbidities were carried out. Particular attention is paid to the acquired α1-PI deficiency in assessing the patients with the proteolysis overactivation and chronic non-inflammatory diseases that are accompanied by the risk factors for the comorbidities progression, and the long-term consequences of COVID-19 initiation. Analyzed data on the search and proteases inhibitory drugs usage in the bronchopulmonary cardiovascular pathologies therapy are essential. It becomes evident the antiviral, anti-inflammatory, anticoagulant, anti-apoptotic effect of α1-PI. The prominent data and prospects for its application as a targeted drug in the SARS-CoV-2 acquired pneumonia and related disorders are presented.

Potential biomarkers identified by tandem mass tags based quantitative proteomics for diagnosis and classification of Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an acute inflammatory autoimmune and demyelinating disease of the peripheral nervous system. Currently, valid biomarkers are unavailable for the diagnosis of GBS. A comparative proteomics analysis was performed on the cerebrospinal fluid (CSF) from 10 patients with GBS and 10 patients with noninflammatory neurological disease (NND) using the tandem mass tags technique. The differentially expressed proteins were analyzed by bioinformatics, and then the candidate proteins were validated by the enzyme-linked immunosorbent assay method in another cohort containing 160 samples (paired CSF and plasma of 40 patients with GBS, CSF of 40 NND patients and plasma of 40 healthy individuals). In all, 298 proteins were successfully identified in the CSF samples, of which 97 differentially expressed proteins were identified in the GBS and NND groups. Three key molecules were identified as candidate molecules for further validation. The CSF levels of TGOLN2 and NCAM1 decreased in GBS patients compared with NND patients, whereas the CSF levels of APOC3 increased. The enzyme-linked immunosorbent assay results were consistent with our proteomics analysis. Interestingly, in the validation cohort, serum APOC3 levels in the GBS group were consistent with those in the CSF samples and significantly higher than those in the healthy control group. Our preliminary data suggest that the CSF protein expression profile of patients with GBS is different from that of patients with NND. Moreover, alterations of TGOLN2, NCAM1and APOC3 may be used as novel biomarkers for identifying patients with GBS.

The contribute of cerebrospinal fluid free light-chain assay in the diagnosis of multiple sclerosis and other neurological diseases in an Italian multicenter study

Background: Cerebrospinal fluid (CSF) free light chains (FLCs) can be an alternative assay to oligoclonal bands (OCBs) in inflammatory neurological disorders, but threshold has no consensus. Objective: To assess the diagnostic accuracy of CSF FLCs in multiple sclerosis (MS) and other neurological diseases. Methods: A total of 406 patients from five Italian centers. FLCs were measured in CSF and serum using Freelite MX assays on Optilite. Results: A total of 171 patients were diagnosed as MS, 154 non-inflammatory neurological diseases, 48 inflammatory central nervous system (CNS) diseases, and 33 peripheral neurological diseases. Both kFLC and λFLC indices were significantly higher in patients with MS compared to other groups (p < 0.0001). The kFLC index ⩾ 6.4 is comparable to OCB for MS diagnosis (area under the receiver operating characteristic curve (AUC) = 0.876; sensitivity 83.6% vs 84.2%; specificity 88.5% vs 90.6%). λFLC index ⩾ 5 showed an AUC of 0.616, sensitivity of 33.3% and specificity of 90.6%. In all, 12/27 (44.4%) MS patients with negative OCB had kFLC index ⩾ 6.4. Interestingly, 37.5% of 24 patients with a single CSF IgG band showed high kFLC index and 12.5% positive λFLC index. Conclusion: Our findings support the diagnostic utility of FLC indices in MS and other CNS inflammatory disorders, suggesting a combined use of FLC and OCB to help clinicians with complementary information.

Integrating imaging and biomarker assessment to better define psoriatic arthritis and predict response to biologic therapy.

The treatment options for PsA have substantially expanded over the last decade. Approximately 40% of patients will not respond to first-line anti-TNF-α therapies. There is limited data to help clinicians select the most appropriate biologic therapy for PsA patients, including guidance for decisions on biologic therapy switching. In this review we will examine the current understanding of predictors of response to treatment. Imaging technology has evolved to allow us to better study psoriatic disease and define disease activity, including synovitis and enthesitis. Enthesitis is implicated in the pathogenesis, diagnosis and prognosis of PsA. It appears to be a common thread among all of the various PsA clinical presentations. Enthesitis mainly manifests as tenderness, which is difficult to distinguish from FM, chronic pain and mechanically associated enthesopathy, and it might be relevant for understanding the apparent 40% failure of existing therapy. Excess adipose tissue makes if more difficult to detect joint swelling clinically, as many PsA patients have very high BMIs. Integrating imaging and clinical assessment with biomarker analysis could help to deliver stratified medicine in PsA and allow better treatment decision making. This could include which patients require ongoing biologic therapy, which class of biologic therapy that should be, and who alternatively requires management of non-inflammatory disease.

Nitrosative Stress Molecules in Multiple Sclerosis: A Meta-Analysis.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system of unknown etiology. As it is still a diagnosis of exclusion, there is an urgent need for biomarkers supporting its diagnosis. Increasing evidence suggests that nitrosative stress may play a pivotal role in the pathogenesis of MS. However, previous reports supporting the role of nitrosative stress molecules as disease biomarkers are inconsistent overall. We therefore systematically analyzed the existing literature to compare the serum and cerebrospinal fluid (CSF) levels of nitrite/nitrate in MS patients with those in patients with noninflammatory other neurological diseases (NIOND) and healthy controls (HC), respectively. We searched the PubMed database and included original articles investigating nitrite/nitrate levels in MS patients and NIOND patients or HC based on predefined selection criteria. Effect sizes were estimated by the standardized mean difference using a random effects model. Our results suggest that MS is associated with higher nitrite/nitrate levels within the CSF compared with patients with NIOND (SMD of 1.51; 95% CI: 0.72, 2.30; p = 0.0008). Likewise, nitrite/nitrate in the CSF of MS patients trends towards increased levels compared with those of HC but does not reach statistical significance (SMD of 3.35; 95% CI: −0.48, 7.19; p = 0.07). Measurement of nitrite/nitrate in the CSF might be a valuable tool facilitating the differentiation of MS and NIOND. Further studies with more homogeneous study criteria are needed to corroborate this hypothesis.