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Molecular sub-characterization of triple-negative breast cancer (TNBC) has great therapeutic and possibly prognostic implications. The primary aim of this study was to investigate the incidence of luminal androgen receptor (LAR) subtype of TNBC and secondary aims were sub-categorization and clinico-pathologic correlation of LAR breast cancers. Retrospective study (January 2008 and 31st of December 2018) consisting of 157 TNBC patients. Androgen receptor (AR) expression was measured by immunohistochemical analysis. One percent cutoff was set as a positive expression. Sub-categorization was done on the basis of EGFR (> 15% of tumor cells) and Ki-67 expression (low- < 11%, intermediate- 11-20%, and high- > 21%). AR expression was correlated with various clinico-pathologic features and outcomes of the patients. The incidence of AR expression in TNBC was 24.8%. Considering different thresholds of > 5%, > 10%, and > 20% immunostaining, the incidence of AR positivity was 18.4, 15.2, and 11.5% respectively. The incidence of Ki-67 (p = 0.89) and EGFR (p = 0.643) expression did not differ significantly in AR-positive and -negative TNBC. Based on EGFR expression 19, 67 and 14% patients were categorized as low, intermediate, and high risk respectively. Low-risk (p ≤ 0.001) and low-grade (p = 0.014) tumors were more likely to have > 10% AR expression. Clinico-pathological profile, response to neoadjuvant chemotherapy, disease-free survival (p = 0.458), and overall survival (p = 0.806) did not significantly differ between AR expressing and negative TNBC. On multivariate analysis, only tumor staging was a significant predictor of survival (p = 0.012) and AR expression of > 10% revealed a trend towards improved survival (p = 0.07). When considering only AR-positive TNBC, AR expression of > 10% (p = 0.038), distant metastases (p = 0.003), and EGFR status (p = 0.024) were significantly associated with survival. AR expression does not seem to very strongly correlate with prognosis in TNBC and further studies could focus more on its predictive role in deciding anti-androgen therapy.
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INTRODUCTION: Non-small cell lung cancer (NSCLC) is the leading cause of mortality globally. Early imaging detection modalities are associated with high false-positive rates and radiation exposure. A non-invasive biomarker can serve as an improvised method for early detection. MicroRNAs can serve as a potential non-invasive biomarker as they are stable in circulation, tissue or biological process-specific, easy to detect, cost-effective, and not associated with radiation hazards. This study validates circulating microRNA in NSCLC of the Indian population and studies its correlation with clinicopathological parameters. MATERIALS AND METHODS: Circulating microRNA (-miR-193b, miR-301a, miR-7, and miR-25) was evaluated in 101 cases of tissue-proven NSCLC and 28 controls in serum samples. RESULTS: There were 67 male and 34 female patients (Male: Female = 1.97:1). The age range was 25 to 86 years with a median age of 60 years. There was a significant upregulation in the expression of miR-193b in the NSCLC group as compared to controls ( P = 0.034). MiR-7 was also upregulated while miR-25 and miR-301a were downregulated in NSCLC as compared to controls; however, a level of significance was not achieved. ROC curve analysis for miR-193b showed an AUC of 0.636 (95% CI, 0.522-0.750; P- value = 0.036) between NSCLC cases and controls. CONCLUSION: The present study showed variable expression of the above-studied miRNAs. MiR-193b showed a significant upregulation in cancer patients; however, the other three miRNAs were not conclusive. This suggests that profiling of microRNA in each population is essential to search for a valid non-invasive biomarker in that population.
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Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , MicroRNA Circulante , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Adulto , MicroRNAs/sangue , MicroRNAs/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Idoso de 80 Anos ou mais , Curva ROC , ÍndiaRESUMO
BACKGROUND & AIMS: Incapacitated regulatory T cells (Tregs) contribute to immune-mediated diseases. Inflammatory Tregs are evident during human inflammatory bowel disease; however, mechanisms driving the development of these cells and their function are not well understood. Therefore, we investigated the role of cellular metabolism in Tregs relevant to gut homeostasis. METHODS: Using human Tregs, we performed mitochondrial ultrastructural studies via electron microscopy and confocal imaging, biochemical and protein analyses using proximity ligation assay, immunoblotting, mass cytometry and fluorescence-activated cell sorting, metabolomics, gene expression analysis, and real-time metabolic profiling utilizing the Seahorse XF analyzer. We used a Crohn's disease single-cell RNA sequencing dataset to infer the therapeutic relevance of targeting metabolic pathways in inflammatory Tregs. We examined the superior functionality of genetically modified Tregs in CD4+ T-cell-induced murine colitis models. RESULTS: Mitochondria-endoplasmic reticulum appositions, known to mediate pyruvate entry into mitochondria via voltage-dependent anion channel 1 (VDAC1), are abundant in Tregs. VDAC1 inhibition perturbed pyruvate metabolism, eliciting sensitization to other inflammatory signals reversible by membrane-permeable methyl pyruvate supplementation. Notably, interleukin (IL) 21 diminished mitochondria-endoplasmic reticulum appositions, resulting in enhanced enzymatic function of glycogen synthase kinase 3 ß, a putative negative regulator of VDAC1, and a hypermetabolic state that amplified Treg inflammatory response. Methyl pyruvate and glycogen synthase kinase 3 ß pharmacologic inhibitor (LY2090314) reversed IL21-induced metabolic rewiring and inflammatory state. Moreover, IL21-induced metabolic genes in Tregs in vitro were enriched in human Crohn's disease intestinal Tregs. Adoptively transferred Il21r-/- Tregs efficiently rescued murine colitis in contrast to wild-type Tregs. CONCLUSIONS: IL21 triggers metabolic dysfunction associated with Treg inflammatory response. Inhibiting IL21-induced metabolism in Tregs may mitigate CD4+ T-cell-driven chronic intestinal inflammation.
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Colite , Mitocôndrias , Animais , Humanos , Camundongos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Doença Crônica , Colite/imunologia , Colite/metabolismo , Colite/patologia , Doença de Crohn/imunologia , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Interleucinas/metabolismo , Interleucinas/farmacologia , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Linfócitos T Reguladores/imunologia , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Canal de Ânion 1 Dependente de Voltagem/genéticaRESUMO
INTRODUCTION: Ampullary adenocarcinoma is a rare neoplasm often treated by the complex Whipple's procedure. Several histological factors predict poor prognosis including pancreatobiliary morphology, presence of lymphovascular, perineural invasion and local or distant metastasis. Systemic therapy with gemcitabine, 5-fluorouracil regimens are given with variable benefits. Immunotherapy checkpoint inhibitors have shown beneficial anti-tumor effects in several carcinomas, the most remarkable being in non-small cell lung cancer. Administration of these novel drugs is based on immunohistochemical expression (which may or may not be indicative of response to therapy) along with meticulous decision making by the multidisciplinary team. Immunohistochemistry (IHC) is an effective means of immune marker demonstration and has been used in various tumor types for predictive and prognostic purposes. METHODS: PD-L1 IHC (clone E1L3N) was applied in 101 cases of ampullary adenocarcinoma. Tumor infiltrating lymphocytes were also evaluated. The immunoreactivity was assessed and categorized into following staining thresholds: <1%, <5%, <10% and ≥10% for tumor cells (membranous and/or cytoplasmic staining pattern), and 5% and 10% cut-offs for immune cells. RESULTS: We found that at a 10% cut-off, 73.3% (74/101) patients were men (P = .006) older than 50 years of age (P < .001) presenting with a tumor measuring <3 cm (P = .001). It was significantly associated with intestinal differentiation (P = .004) and grade 1 tumors (P = .001). Twelve patients presented with recurrence as well (P = .03). CONCLUSION: In the context of ampullary adenocarcinoma, this study highlights the positivity observed with the PD-L1 IHC clone E1L3N at different thresholds, with the particularly stronger associations being evident at a 10% cut-off.
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Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias do Ducto Colédoco , Neoplasias Duodenais , Neoplasias Pulmonares , Neoplasias Pancreáticas , Masculino , Humanos , Feminino , Antígeno B7-H1 , Adenocarcinoma/tratamento farmacológico , Neoplasias Duodenais/tratamento farmacológicoRESUMO
Objectives Methotrexate (MTX) has anticancer therapeutic potential with multiple doses-related adverse effects and toxicities. Immunoassays for therapeutic monitoring of serum MTX have their own limitations. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is considered as the reference method; however, commercially availability of them is limited. We aimed to adapt/develop an in-house LC-MS/MS method for therapeutic monitoring of serum MTX. Materials and Methods Serum protein precipitation was performed using acetonitrile-water containing 250 µM solution of aminoacetophenone as internal standard (IS). Chromatographic separation was achieved on a C18 column with mobile phase of 0.1% solution of formic acid (solvent A) and acetonitrile (solvent B) at a flow rate of 0.4 mL/min. MS was performed under positive ion mode with mass transition for MTX and IS as m/z 455.1â308.1 and 136.2â94.1, respectively. The method was validated by following Bioanalytical Method Validation Guidance for Industry, 2018 and applied on leukemia patients' samples on MTX therapy. Results The correlation coefficient of eight serially diluted calibration standards of 0.09 to 12.5 µM was >0.99 and had linearity with > 95% precision and accuracy at analytical quality control levels. The lower limit of MTX quantification achieved was 0.09 µM with good intensity and sharp peak as compared with blank sample. The total run time of the assay was 5 minutes. The serum MTX levels obtained by this method in leukemia patients exhibited clinical correlation and an excellent agreement with commercial immunoassay used in parallel. Conclusion We were able to develop a rapid, sensitive, and cost-effective LC-MS/MS method suitable for therapeutic drug monitoring of MTX in routine clinical diagnostic laboratories.
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Ampulla is a complex region located at the confluence of pancreatic and common bile duct and intestinal epithelium. Tumors arising in this region are anatomically and morphologically heterogenous, however they show unique as well as overlapping molecular features. Cancers of both these anatomic sites share morphological as well as genetic profile despite having few unique differences. Targeted therapies are currently emerging as one of the demanding approaches for treatment in most cancer types especially for malignant epithelial tumors and therefore genetic profiling of cancers is the key for identification of potentially therapeutic targetable mutations to know their prevalence and prognostic impact. We studied 97 resected cases of formalin fixed paraffin-embedded AC by deep targeted sequencing using Ampliseq cancer hotspot panel comprising of 50 oncogenes and tumor suppressor genes. Potentially therapeutic targetable mutations were observed in 58/83 (70%) cases. Fourteen patients did not show any pathogenic mutation. TP53 (48.1%), KRAS (37.3%), APC (25.3%), SMAD4 (22.8%), MET (16.8%), CTNNB1 (15.6%) and PIK3CA (10.8%) were the major mutated potential therapeutic targets. KRAS mutation (43.2 Vs. 32.6%) was more prevalent in pancreatobiliary subtype, while TP53 (58.6 Vs 35.1), APC (36.9 Vs 10.8), SMAD4 (28.2 Vs 16.2), MET (21.7 Vs 10.8) and CTNNB1 (19.5 Vs 10.8) were more prevalent in intestinal subtype. WNT signaling pathway was the major altered pathway in intestinal subtype. These mutated genes and pathways may be targeted with currently available drugs and may be explored for future development of targetable agents to improve the disease course in patients of AC.
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Ampola Hepatopancreática/patologia , Biomarcadores Tumorais/genética , Neoplasias do Ducto Colédoco/epidemiologia , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/metabolismo , Neoplasias do Ducto Colédoco/genética , Neoplasias do Ducto Colédoco/patologia , Feminino , Seguimentos , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , PrognósticoRESUMO
BACKGROUND: The genetic landscape of intestinal (INT) and pancreatobiliary (PB) type ampullary cancer (AC) has been evolving with distinct as well as overlapping molecular profiles. METHODS: We performed whole-exome sequencing in 37 cases of AC to identify the targetable molecular profiles of INT and PB tumors. Paired tumor-normal sequencing was performed on the HiSeq 2500 Illumina platform. RESULTS: There were 22 INT, 13 PB, and two cases of mixed differentiation of AC that exhibited a total of 1,263 somatic variants in 112 genes (2-257 variants/case) with 183 somatic deleterious variants. INT showed variations in 78 genes (1-31/case), while PB showed variations in 51 genes (1-29/case). Targetable mutations involving one or more major pathways were found in 86.5% of all ACs. Mutations in APC, CTNNB1, SMAD4, KMT2, EPHA, ERBB, and Notch genes were more frequent in INT tumors, while chromatin remodeling complex mutations were frequent in PB tumors. In the major signaling pathways, the phosphoinositide 3-kinase (PI3)/AKT and RAS/mitogen-activated protein kinase (MAPK) pathways were significantly mutated in 70% of cases (82% INT, 46% PB, p = .023), with PI3/AKT mutation being more frequent in INT and RAS/MAPK in PB tumors. Tumor mutation burden was low in both differentiation types, with 1.6/Mb in INT and 0.8/Mb in PB types (p =.217). CONCLUSIONS: The exome data suggest that INT types are genetically more unstable than PB and involve mutations in tumor suppressors, oncogenes, transcription factors, and chromatin remodeling genes. The spectra of the genetic profiles of INT and PB types suggested primary targeting of PI3/AKT in INT and RAS/RAF and PI3/AKT pathways in PB carcinomas.
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BACKGROUND: Ampullary cancer may occur as a component of hereditary cancer syndromes. Mutations in inherited cancer susceptibility genes play a therapeutic role and its knowledge in ampullary cancer is lacking. METHODS: Thirty-seven cases of ampullary carcinoma were subjected to tumor-normal whole exome sequencing with mean coverage of 100X (blood) and 200X (tumor). Data were analyzed and correlated with intestinal and pancreatobiliary differentiation. RESULTS: There were 22 intestinal, 13 pancreatobiliary and 2 cases of mixed differentiation. One hundred and forty-three germline variations with at least >1 pathogenic germline variants (PGVs) across 83 genes were found in 36 of 37 patients. Twelve genes (14.5 %) showed >3, 20 genes (24.1 %) showed two and 51 genes (61.4 %) showed one PGVs. Intestinal differentiation showed higher PGVs (117 variants, 73 genes) than pancreatobiliary differentiation (85 variants, 62 genes). PGVs in ERCC5, MEN1, MSH3, CHEK1, TP53, APC, FANCA, ERBB2, BRCA1, BRCA2, RTEL1, HNF1A and PTCH1 were seen in >50 % of cases. Nine genes harbored somatic second hits in 14 cases. PGVs in DNA damage-repair, homologous recombination repair, TP53 transcriptional regulation, DNA double stranded breaks, cell cycle and nucleotide excision repair genes were seen in all cases of intestinal and pancreatobiliary differentiation, while DNA mismatch repair genes were found in 81.8 % of intestinal and 84.6 % of pancreatobiliary cancers. Functional pathway analysis showed that DNA damage-repair, double stranded break repair, mismatch repair, homologous recombination repair and TP53 transcriptional regulation genes were altered in both while nucleotide-excision repair was significantly mutated in intestinal type and cell-cycle genes in pancreatobiliary type (p < 0.05). CONCLUSION: This study reports spectrum of PGVs in intestinal and pancreatobiliary differentiation of ampullary carcinoma at higher frequency through whole exome sequencing. PGVs were most frequently found in DNA repair genes. Detecting PGVs through tumor-normal sequencing may identify therapeutically actionable and double-hit mutations that can guide towards appropriate management.
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Ampola Hepatopancreática/patologia , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Neoplasias do Ducto Colédoco/genética , Neoplasias Duodenais/genética , Mutação em Linhagem Germinativa , Neoplasias Pancreáticas/genética , Adulto , Idoso , Carcinoma Ductal Pancreático/patologia , Neoplasias do Ducto Colédoco/patologia , Análise Mutacional de DNA , Neoplasias Duodenais/patologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Neoplasias Pancreáticas/patologia , Fenótipo , Sequenciamento do Exoma , Adulto JovemRESUMO
PURPOSE: The primary aim of this study was to determine the incidence of estrogen receptor α (ERα), estrogen receptor ß (ERß), and human epidermal growth factor receptor 2 (HER-2) expression in various subtypes of thyroid carcinoma (TC) of follicular origin and the secondary aim was to correlate the expression with various clinicopathologic prognostic factors. METHODS: Immunohistochemistry analysis was performed on archival paraffin-embedded tissue sections (1991-2016). ERα, ERß, and HER-2 expressions were correlated with clinicopathologic prognostic factors, disease recurrence, and overall survival (OS). RESULTS: A total of 264 TC patients were included in the study. Incidences of ERα, ERß, and HER-2 were 8.1 vs 16.3 vs 13.9% (p=0.15), 26.6 vs 11.5 vs 36.1% (p=0.002), and 12.9 vs 2.9 vs 0% (p=0.003) in papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and poorly differentiated thyroid carcinoma (PDTC), respectively. Overall ERα had significant correlation with distant metastases (0.038) and in case of PDTC with multicentricity (p=0.037). ERß had significant correlation with lymph node metastases (p=0.023) in FTC. HER-2 correlated with tumor size (p=0.027) only on univariate analysis. OS did not correlate with expression of any receptor. CONCLUSION: ERα, ERß, and HER-2 have differential expression and prognostic implications in different TC subtypes.
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Hepatitis B virus (HBV) infects the liver, causing cirrhosis and cancer. In developed countries, five international guidelines have been used to make a decision for the management of patients with chronic HBV infection. In this review, since the guidelines were established by clinical and epidemiological data of developed countries, we aimed to evaluate whether (1) HBV patient profiles of developing countries are similar to developed countries, and (2) which guideline can be applicable to resource-limited developing countries. First, as an example of the most recent data of HBV infections among developing countries, we evaluated the national HBV viral load study in Nepal, which were compared with the data from other developing countries. In Nepal, the highest number of patients had viral loads of 20-2000 IU/mL (36.7%) and belonged to the age group of 21-30 years; HBV epidemiology in Nepal, based on the viral loads, gender, and age groups was similar to those of not only other developing countries but also developed countries. Next, we reviewed five international HBV treatment guidelines of the World Health Organization (WHO), American Association for the Study of Liver Diseases (AASLD), National Institute for Health and Care Excellence (NICE), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL). All guidelines require the viral load and alanine aminotransferase (ALT) levels for decision making. Although four guidelines recommend elastography to assess liver cirrhosis, the WHO guideline alternatively recommends using the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), which is inexpensive and conducted routinely in most hospitals. Therefore, in resource-limited developing countries like Nepal, we recommend the WHO guideline for HBV treatment based on the viral load, ALT, and APRI information.
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Gallbladder carcinoma (GBC) is the most aggressive gastrointestinal malignancy throughout the world, with wide geographical variance. It is the subtype of biliary tract malignancy that has the poorest prognosis and lower survival among all biliary tract malignancies. Various factors are associated with GBC pathogenesis such as environmental, microbial, metabolic and molecular. Chronic inflammation of gallbladder due to presence of gallstone or microbial infection (eg. Salmonella or H. pylori) results in sustained production of inflammatory mediators in the tissue microenvironment, which can cause genomic changes linked to carcinogenesis. Genetic alterations are one of the major factors, associated with aggressiveness and prognosis. Researches have been done to explore suitable biomarker for early diagnosis and identify altered molecular pathways to develop appropriate biomarkers for early diagnosis, therapy and predicting prognosis. Different agents for targeted therapy against actionable mutations of molecules like EGFR, VEGF, mTOR, HER2, PDL-1, PD-1, MET, PI3K, N-cadherin, VEGFR, MEK1 and MEK2 are being tried. Despite these advancements, there is dismal improvement in the survival of GBC patients. Genetic aberrations other than actionable mutations and epigenetic modification including aberrant expressions of micro-RNAs, are also being studied both as diagnostic biomarker and therapeutic targets. Complex pathogenesis of GBC still needs to be unfolded. In this review we focus on the molecular pathogenesis of GBC elucidated till date along with future directions that can be explored to achieve better management of GBC patients.
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Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/patologia , Transdução de Sinais/genética , Biomarcadores Tumorais/genética , Epigênese Genética/genética , Humanos , MicroRNAs/genética , PrognósticoRESUMO
BACKGROUND: Epidermal growth factor receptor (EGFR) mutation is the most frequent mutation tested in lung cancer for targeted therapy in the era of personalized medicine. Knowledge about EGFR mutation is constantly expanding regarding its frequency, clinicopathological association, advancements in testing methodology and sample requirement. We investigated EGFR mutation frequency in non-small cell lung cancer (NSCLC) in North Indian patients and evaluated its diagnostic performance in cytological samples. METHODS: Molecular EGFR testing was done in 250 cases of NSCLC by both real-time polymerase chain reaction (PCR) (Therascreen) and mutation-specific EGFR immunohistochemistry (IHC). Thirty cases had both cytology samples and biopsy including 20 pleural effusions and 10 fine-needle aspirates. EGFR mutation concordance between pleural effusion and biopsy was studied. RESULTS: EGFR mutation was overall 31.6% in NSCLC with 36.5% in adenocarcinoma and 15% in squamous cell carcinoma. L858R mutation accounted for 50.7% and DEL19 for 39.3% of total EGFR mutations. Complex mutations were seen in 2% of cases. Sensitivity of mutation-specific EGFR IHC was 48.3% and specificity was 92.3%. L858R showed higher sensitivity (55% vs. 33.3%) but similar specificity (93.2% vs. 91.3%) compared to DEL19. EGFR mutation was successful in 95% of pleural effusion and showed 83.3% concordance with tissue biopsy. CONCLUSIONS: EGFR mutation frequency in North Indian patients was comparable to that of Asia-Pacific region and showed a similar pattern of histological distribution. EGFR mutation in squamous cell carcinomas is increasingly recognized which was 15% in our study. Mutation-specific EGFR IHC shows variable but generally low sensitivity and considering its significant pre- and post-analytical variables, it should be highly discouraged in patient management. Cytological samples may not only serve as suitable alternative but may be complementary to tissue biopsies.
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Takayasu arteritis (TA) is a large vessel vasculitis of unknown pathogenesis. Assessment of disease activity is a challenge, and there is an unmet need for relevant biomarker(s). In our previous study, NMR based serum metabolomics had revealed distinctive metabolic signatures in TA patients compared with age/sex matched healthy controls and systemic lupus erythematosus (SLE). In this study we investigate whether the metabolites correlate with disease activity. Patients with TA fulfilling American College of Rheumatology (ACR) criteria were enrolled, and disease activity was assessed using Indian Takayasu Clinical Activity Score using acute phase reactant-erythrocyte sedimentation rate [ITAS-A (ESR)]. Sera were analyzed using 800 MHz NMR spectrometer to identify metabolites [based on partial least squares discriminant analysis (PLS-DA) VIP (variable importance in projection) score > 1.0 and permutation test, p-value <0.01]. 45 active and 53 inactive TA patients with median age 27 [(IQR) 22-35 years] and 27 [(IQR) 23-37 years], female to male ratio 3.5:1 and 4.9:1, and median duration of illness 5 [(IQR) 2-9 years] and 3 [(IQR) 1-6 years], respectively, were enrolled. The key metabolites with highest discriminatory potential in active TA (ITAS-A ≥ 4) were glutamate and N-acetyl glycoprotein (NAG), both elevated, with area under the curve 0.775 and 0.769 ( p-value <0.001). On follow up assessment, metabolic spectra started to differ with change in disease activity. This large cohort of patients revealed metabolic profiles discriminating between clinically active and inactive TA patients. It suggests glutamate and NAG have strong potential as biomarkers for disease activity in TA and may serve as a guide to therapy. We are now working to further validate these results in longitudinal studies.