ADA Levels Research Articles

Clinical value of cerebrospinal fluid ADA, IL-23 joint detection in the diagnosis of tuberculous meningitis related diseases

Objective To evaluate the clinical value of cerebrospinal fluid ADA, IL-23 joint detection in the diagnosis of tuberculous meningitis related diseases. Methods 253 cases with tuberculous meningitis related diseases were selected as the research subjects.According to the diagnosis, they were divided into tuberculous meningitis group (meningitis group, 138 cases), tuberculous meningitis complicated with hydrocephalus group (hydrocephalus group, 35 cases) and control group(80 cases). All patients after admission received lumbar puncture, the part of cerebrospinal fluid specimens were inspected, the cerebrospinal fluid ADA, IL-23 joint test was conducted.Meningitis group and hydrocephalus group were given anti-TB drugs(INH, RFP and PZA+ sm) combined with chemotherapy.3 months after treatment, the meningitis group and hydrocephalus group received lumbar puncture cerebrospinal fluid ADA, IL-23 joint test again.The levels of ADA, IL-23 in cerebrospinal fluid were compared. Results Before treatment, cerebrospinal fluid ADA, IL-23 levels in the meningitis group were (12.64±5.54)u/L and (48.38±10.78)pg/mL, those in the hydrocephalus group were (15.81±6.92)u/L and (77.21±13.42 mm)pg/mL, which in the control group were (3.21±2.20)u/L and (9.05±3.89)pg/mL, ADA, IL-23 levels in meningitis group and hydrocephalus group before treatment were significantly higher than the control group(F=117.24, 724.97, P<0.001). Spearma analysis showed that each group of cerebrospinal fluid ADA and IL-23 had no correlation.After treatment, the cerebrospinal fluid ADA, IL-23 levels in the meningitis group were (3.79±3.13)u/L and (13.46±6.62)pg/mL, which in the hydrocephalus group were (6.42±4.35)u/L and (25.42±8.54)pg/mL, the meningitis group before and after treatment had statistically significant differences in cerebrospinal fluid ADA, IL-23 (t=16.34, 32.43, all P<0.001); hydrocephalus group before and after treatment had statistically significant differences in cerebrospinal fluid ADA, IL-23 (t=6.80, 19.26, all P<0.001). Conclusion Cerebrospinal fluid ADA, IL-23 joint detection in the early diagnosis of tuberculous meningitis related diseases and clinical observation has high clinical value. Key words: Meningitis, tuberculous; Hydrocephalus; Adenosine deaminase; Interleukin-23

Mycobacterium tuberculosis ESAT6 and CPF10 Induce Adenosine Deaminase 2 mRNA Expression in Monocyte-Derived Macrophages.

BackgroundDelayed hypersensitivity plays a large role in the pathogenesis of tuberculous pleural effusion (TPE). Macrophages infected with live Mycobacterium tuberculosis (MTB) increase the levels of adenosine deaminase2 (ADA2) in the pleural fluid of TPE patients. However, it is as yet unclear whether ADA2 can be produced by macrophages when challenged with MTB antigens alone. This study therefore evaluated the levels of ADA2 mRNA expression, using monocyte-derived macrophages (MDMs) stimulated with MTB antigens.MethodsPurified monocytes from the peripheral blood mononuclear cells of healthy volunteers were differentiated into macrophages using granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF). The MDMs were stimulated with early secretory antigenic target protein 6 (ESAT6) and culture filtrate protein 10 (CFP10). The mRNA expression levels for the cat eye syndrome chromosome region, candidate 1 (CECR1) gene encoding ADA2 were then measured.ResultsCECR1 mRNA expression levels were significantly higher in MDMs stimulated with ESAT6 and CFP10, than in the unstimulated MDMs. When stimulated with ESAT6, M-CSF-treated MDMs showed more pronounced CECR1 mRNA expression than GM-CSF-treated MDMs. Interferon-γ decreased the ESAT6- and CFP10-induced CECR1 mRNA expression in MDMs. CECR1 mRNA expression levels were positively correlated with mRNA expression of tumor necrosis factor α and interleukin 10, respectively.ConclusionADA2 mRNA expression increased when MDMs were stimulated with MTB antigens alone. This partly indicates that pleural fluid ADA levels could increase in patients with culture-negative TPE. Our results may be helpful in improving the understanding of TPE pathogenesis.

Pleural Fluid Adenosine Deaminase Values in Diagnosis of Tuberculous Pleural Effusion in South Khorasan Province

Background: Due to variability of pleural fluid ADA measures in pleural tuberculosis, researchers have recommended the necessity of regional studies for determination of specific regional values. Objectives: The purpose of the present study was to evaluate the values of pleural fluid ADA in diagnosis of Tuberculous pleural effusion in South Khorasan province. Methods: A cross-sectional study was conducted on patients > 12 years old with exudative pleural effusion in South Khorasan province (east of Iran). Light criteria were used to define exudative effusion. Total ADA was determined calorimetrically by Diazyme ADA assay. The data were analyzed using t test, ANOVA and χ2 tests through Spss 16 version software. Results: We studied 255 cases including 139 (54.5%) males and 116 (45.5%) females with mean age of 63.8 ± 18 years. There were 36 (14.1%) cases with Tuberculous pleural effusion and 219 (85.9%) cases of non-Tuberculous pleural effusion. Malignant and acute bacterial infection comprise 106 (41.6%) and 29 cases (11.4%), respectively. The mean levels and optimal cut off point of ADA in Tuberculous pleural effusion were40.2 ± 24.7 and 30 IU/L respectively. ADA in Tuberculous pleural effusion showed negative correlation with age (r = -0.40, p = 0.01), but weak positive correlation with fluid protein(r = 0.44, P = 0.007) and LDH (r = 0.32, P = 05). Conclusions: Mean and cut off point of ADA was relatively low in patients with Tuberculous pleural effusion in South Khorasan province. The age of patients and fluid levels of protein, and LDH must be considered in interpretation of pleural fluid ADA levels.

Comparison of the diagnostic utility of ADA and CA125 in tuberculous effusion

BackgroundPleural effusion can be due to various pleural infections like TB as well as neoplasia. CA125 is a tumor marker found on the surface of ovarian and other normal cells as pleural cells. CA125 has been found to increase in serum and hence pleural fluid of patients with pleural effusion due to malignancy as well as due to TB.This study was conducted to evaluate the utility of CA125 in the diagnosis of pleural effusion resulting from TB, malignancy and pneumonia as well as to evaluate and compare the diagnostic utility of CA125 and ADA in the diagnosis of TB effusion. Patients and methods20 patients with tuberculous effusion (group I), 20 patients with malignant effusion (group II) and 20 patients with parapneumonic effusions (group III) were evaluated for the levels of CA125 and ADA in their pleural fluid. In malignant cases, diagnosis was made through microscopic inspection of pleural biopsy samples and cytology of pleural fluid. For diagnosis of tuberculosis, Ziehl Neelsen sputum smear, pleural fluid smear and/ or culture. Parapneumonic effusions were confirmed by pleural fluid cell count and culture & sensitivity. ResultsThe mean±SD level of CA125 in pleural fluid was 41.732±20.744U/ml, 309.27±79.564U/ml and 7.040±5.601U/ml in tuberculous, malignant and parapneumonic effusions respectively; which showed a statistically significant difference between the three groups (p<0.01). Pleural fluid CA125 was significantly higher in group II than group I (P1=0.000), and group III (P3=0.000). Pleural fluid CA125 was significantly higher in group I than group III (P2=0.000). Pleural fluid ADA was significantly higher in group I than group II (P1=0.000) and group III (P2=0.000). For diagnosing TB, CA125 showed a sensitivity and specificity of 74.1%, 76.9%, respectively while ADA demonstrated a sensitivity and specificity of 75% and 75% respectively. ConclusionCA-125 levels in pleural fluid may be used for differentiation between TB, pneumonic, and malignancy-induced effusions.Also CA125 may be added to the diagnostic workup of pleural fluid for accurate diagnosis of TB effusion.

Detection of anti-infliximab antibodies is impacted by antibody titer, infliximab level and IgG4 antibodies: a systematic comparison of three different assays.

Background:There is scant information on the accuracy of different assays used to measure anti-infliximab antibodies (ADAs), especially in the presence of detectable infliximab (IFX). We thus aimed to evaluate and compare three different assays for the detection of IFX and ADAs and to clarify the impact of the presence of circulating IFX on the accuracy of the ADA assays.Methods:Blood samples from 79 ulcerative colitis (UC) patients treated with infliximab were assessed for IFX levels and ADAs using three different assays: an in-house assay and two commercial kits, Immundiagnostik and Theradiag. Sera samples with ADAs and undetectable levels of IFX were spiked with exogenous IFX and analyzed for ADAs.Results:The three assays showed 81–96% agreement for the measured IFX level. However, the in-house assay and Immundiagnostik assays detected ADAs in 34 out of 79 samples, whereas Theradiag only detected ADAs in 24 samples. Samples negative for ADAs with Theradiag, but ADA-positive in both the in-house and Immundiagnostik assays, were positive for IFX or IgG4 ADAs. In spiking experiments, a low concentration of exogenous IFX (5 µg/ml) hampered ADA detection with Theradiag in sera samples with ADA levels of between 3 and 10 µg/ml. In the Immundiagnostik assay detection interference was only observed at concentrations of exogenous IFX higher than 30 µg/ml. However, in samples with high levels of ADAs (>25 µg/ml) interference was only observed at IFX concentrations higher than 100 µg/ml in all three assays. Binary (IFX/ADA) stratification of the results showed that IFX+/ADA- and IFX-/ADAs+ were less influenced by the assay results than the double-positive (IFX+/ADAs+) and double-negative (IFX-/ADAs-) combination.Conclusions:All three methodologies are equally suitable for measuring IFX levels. However, erroneous therapeutic decisions may occur when patients show double-negative (IFX-/ADAs-) or double-positive (IFX+/ADAs+) status, since agreement between assays is significantly lower in these circumstances.

PWE-029 Utility of Measurement Anti TNF Drug and Anti Drug Antibody Levels in A Cohort of Patients with Crohn’s Disease: How Does it Affect Clinical Practice?: Abstract PWE-029 Table 1

Introduction It has been recognised that the measurement of anti-TNF drug concentrations and detection of anti drug antibodies may be useful in aiding decision making and therefore optimising clinical outcomes in patients on anti-TNF drugs in whom there is incomplete clinical response or loss of drug therapy. 1 Methods A total of 45 Crohn’s patients attending our tertiary referral IBD clinic had anti TNF drug concentrations and antidrug antibodies levels measured. The indications for testing were incomplete response or loss of response during therapy. We measured drug levels and Anti Drug Antibody levels using the ELISA assay (Immunodiagnostik). Reference ranges for Infliximab >2.0 ug/ml therapeutic and Adalimumab >5.0 ug/ml therapeutic. Total drug antibody levels >10 AU/ml positive. Results We present the patient demographics in Table 1. Drug and ADA levels 44% (n = 20) had therapeutic levels and negative antibodies, 18% (n = 8) had therapeutic levels and positive antibodies, 22% (n = 10) had sub-therapeutic levels and negative antibodies and 16% (n = 7) had sub-therapeutic levels and positive antibodies. Impact of results meaurement of drug and ADA led to change in management in 28/45 (62%) patients. 6 (13%) patients switched therapy,17 (38%) had dose escalation,17 (38%) no treatment change,5 (11%)other outcome. Conclusion Measurement of anti-TNF drug concentrations and antibody status in our patients on Anti TNF resulted in change of management in 28/45 (62%) patients. In the 17 patients with dose escalation in whom outcome was assessed 13 (76%) patients have responded. Measurement of drug concentration and antibody status presents an possible option in the management of patients on anti-TNF who present with loss of response or incomplete response of treatment Reference 1 Vande Casteele N, et al. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn’s disease. GUT 2015 Oct; 64 (10):1539–45. Disclosure of Interest S. Laird: None Declared, L. Caulfield: None Declared, L. Smith Conflict with: cook, boston and allergan, almirall, J. Winter Conflict with: almirall, reckitt-Benckisaer, ferring, shire, D. Gaya: None Declared, A. Morris Conflict with: Falk,Vifor

A Case of Primary Pleural Malignant Lymphoma Accompanied with High ADA Level in Pleural Effusion.

A Case of Primary Pleural Malignant Lymphoma Accompanied with High ADA Level in Pleural Effusion.

Estimation of Adenosine deaminase and proteinase inhibitory activity and their correlation with tuberculous effusion and other pleural effusion cases

Introduction: Diagnosis of tuberculous effusion is difficult with the conventional, bacteriological, cytological and histopathological methods in our country. Adenosine deaminase, serum proteins, phospholipids show marked variation in tuberculous exudates. Material and Methods: Twenty cases of pulmonary tuberculosis, 10 cases of malignant effusions and 8 cases of other para-pneumonic effusions visiting a tertiary care hospital were included in this study. After collecting blood and pleural fluid samples, Adenosine deaminase, Alpha-1 antitrypsin l, proteinase inhibitor activity, total lipid levels, phospholipid and Lipase activity were estimated. Observation and results: Serum ADA levels in tuberculous effusion was 21.8+ 9.8 U/L(10-45.08) P

PTU-075 Utility of measuring adalimumab drug levels and anti-drug antibodies in clinical practice: a large IBD referral centre experience

Introduction The development of adalimumab (Ada) drug and antibody testing has allowed a personalised approach to complex inflammatory bowel disease (IBD) treatment. We present our 2-year experience at a tertiary IBD referral centre. Method All Ada drug and antibody levels carried out at Guy’s and St. Thomas’ Hospital were analysed. The indications for carrying out levels, the subsequent changes in management and the long-term patient outcomes were evaluated. Results 143 levels were carried out on 105 patients from October 2012 to October 2014. The median value was 5 µg/ml (range 0- >8 µg/ml). 74 levels (52%) were done on patients who had symptoms indicative of loss of response (LOR). 13 patients, all with no detectable antibodies had their dose increased, 10 of these patients had low levels ( 5 levels (4%) were measured after induction (week 12–14) resulting in 1 patient with a low level (3.5 µg/ml) and clinically active disease escalating to 40 mg weekly with good response. 38 levels (27%) were done as part of annual reassessment resulting in only 2 changes in management: 1 patient had dose de-escalation from weekly to every other week due to levels >8 µg/ml and the other had their dose increased to weekly due to low levels (1.4 µg/ml). The remaining levels were done to aid decisions regarding discontinuation of concomitant immunosuppressant (1%), dose de-escalation (11%) and discontinuation of Ada (2%), or to assess response to dose escalation (3%). 39 (27%) of the levels were sub therapeutic in 32 patients. In the 30 patients that did not have antibodies to Ada, 13 patients underwent dose escalation. Ada antibodies were detected in only 2 patients (1%). 1 patient, who had previously had a reaction to infliximab continued on Ada with minimal improvement in her symptoms. The other patient was lost to follow-up shortly after the levels were tested. Conclusion Measuring Ada levels in our cohort resulted in a change of management for 25% of patients, a percentage similar to that seen for infliximab. The majority of patients with LOR who had sub therapeutic levels responded well to Ada dose escalation. Antidrug antibody development is infrequent in our cohort of patients. Disclosure of interest B. Warner: None Declared, E. Johnston: None Declared, J. Digby-Bell: None Declared, N. Unsworth: None Declared, S. Anderson: None Declared, J. Sanderson: None Declared, Z. Arkir: None Declared, P. Irving Speaker Bureau of: MSD, Abbvie and Takeda.

Modeling of the Fasting Plasma Glucose Identified an Equation Providing Significantly Earlier Identification of Overt Type 2 Diabetes in Nonhuman Primates (NHPs)

In type 2 diabetes, both identification of causation and initiation of prevention efforts are likely optimized if initiated at the earliest point in the disease progression; we therefore sought to determine if a better diagnostic threshold for fasting plasma glucose (FPG) than the current ADA level (FPG 蠅 126 mg/dl) might be defined while balancing sensitivity and specificity. Longitudinal data were obtained under a constant environment and a healthy diet from NHPs that frequently and spontaneously develop the same type 2 diabetes as occurs in humans. Mathematical modeling of the exponential relationship between glucose (Y) and age (X) identified the natural breakpoint in the progression to diabetes. When Y was replaced with -100/Y and X with X3, the plot for -100/Y against X3 revealed a strong linear relationship, with the optimal equation of best fit: Y = 1/[-a/100-(b/100)X3]. Using regression analysis a significant change in slope for each monkey was identified at the FPG of 83±14 mg/dl. By contrast, if diabetes was defined using either the 126 mg/dl or the 100 mg/dl levels, the diagnosis was delayed by 2.2 and 1.4 years respectively. Of a population of 267 rhesus monkeys studied longitudinally, all monkeys with 2 consecutive FPG levels >80 mg/dl progressed to diabetes or died enroute with significantly impaired glucose tolerance. These data reveal that a significantly lower FPG for the diagnosis of diabetes should be considered to optimize causal investigations and prevention efforts.

Isolated nuclear III nerve paresis secondary to neurocysticercosis showing spontaneous clinical improvement.

Sir, We wish to present a case of isolated nuclear IIIrd nerve paresis secondary to neurocysticercosis (NCC) showing spontaneous clinical improvement. Isolated third cranial nerve palsy is rare in NCC. A 14-year-old male child of Nepali origin presented with diplopia for 6 days in left lateral gaze and drooping of his upper eyelids in both eyes. The complaints were insidious in onset, non-progressive simultaneous in both eyes with no diurnal fluctuation. Rest of his present and past medical history was not significant. He had history of pork consumption. His general physical examination and systemic examination including neurological examination was unremarkable. His visual acuity was 6/6 OU with increased wrinkling on forehead. He had severe neurological ptosis in both eyes with poor levator palpebrae superioris (LPS) action with no Marcus Gunn phenomenon and no sign s/o fatigueability. He also had an exotropia of about 15 degree and mild paresis of elevation of eyeball in right eye maximum in lateral gaze. He had mild paresis of his right medial rectus with end gaze nystagmus in left gaze. Rest of the ophthalmological examination was unremarkable including papillary reactions. Diplopia charting showed horizontal diplopia in all gaze positions with maximum difference in left lateral gaze positions [Figure 1]. While waiting for his investigation reports his sign and symptoms showed spontaneous clinical improvement. His magnetic resonance imaging (MRI) showed a solitary ring-enhancing lesion in the pre-aqueductal region of mid brain of size 0.72 × 0.68 cm involving IIIrd nerve nucleus with peri lesional edema [Figure 2]. His lumbar puncture was done and it revealed CSF protein levels 60 and it also showed 9 white blood cells mainly lymphocytes. ADA levels in his CSF were within normal limit. His serology revealed positive IgG levels for taenia solium (1.13 U/ml) by ELISA. In the light of the above findings the patient was diagnosed as a case of nuclear third nerve paresis secondary to NCC of brainstem. After consultation with Department of Neurology the patient was put on oral albendazole and prednisolone. He was continuously followed up with no similar episodes till 1 year after. Figure 1 (a) Ptosis in both eyes. (b) Paresis of Medial rectus in right eye. (c) Paresis of elevation in right eye. (d-f) Respective improvement Figure 2 Transverse section in MRI showing solitary ring enhancing lesion in the pre-aqueductal region of mid brain of size 0.72 × 0.68 cm involving IIIrd nerve nucleus with peri lesional edema NCC is the most common parasitic infestation of the nervous system.[1] Globally, NCC is endemic in Central and South America, sub-Saharan Africa, and in some regions of the Far East, including the Indian subcontinent, Indonesia, and China, reaching an incidence of 3.6% in some regions.[1] Del Brutto et al. have suggested diagnostic criteria for NCC.[2] In our case these criteria were fulfilled for probable diagnosis of NCC. It usually presents with seizures. Other various CNS clinical manifestations include headache, hydrocephalus, chronic meningitis, focal neurological deficits, dementia and psychiatric manifestations.[3] Involvement of third nerve is rare especially due to a parenchymal lesion.[4] Fluctuation in perilesional edema was probably responsible for spontaneous clinical recovery in our patient. The lesion in such nuclear third nerve paresis involves the central caudal nucleus (CCN), which is a small subgroup of oculomotor nucleus containing subnucleus for levator palpebrae superioris.[5] Involvement of this nucleus results in complete, bilateral ptosis. We propose a more detailed evaluation of patients with fluctuating ptosis. In those patients where ptosis is restricted to ocular muscle without any other neuromuscular involvement, cranial imaging needs to be done, preferably MRI of the brain with contrast studies that may show lesions in the midbrain.

Role of thoracentesis in the management of tuberculous pleural effusion

BackgroundTuberculous pleural effusion (TPE) is the second most common form of extrapulmonary tuberculosis (EPTB). Up to 50% after treatment complicated with pleural thickening. Pleural biopsy has been considered the gold standard in diagnosis of TPE but it is invasive, so that pleural fluid markers of TPE have been extensively evaluated as an alternative to pleural biopsy. Thoracentesis for measuring these fluid markers is important. AimAssessing the value of diagnostic thoracentesis (by measuring pleural adenosine deaminase levels) and role of therapeutic thoracentesis in preventing pleural thickening. Subjects and methods10 cases with transudative pleural effusion and 45 cases with already diagnosed exudative effusion (30 cases of TPE, and 15 cases of Malignant PE) were included. 50ml pleural fluid samples were aspirated and sent for measuring ADA levels. The 30 cases of TPE were classified into 2 equal groups the 1st group started 6months anti tuberculous therapy plus repeated thoracentesis while the 2nd started anti tuberculous therapy only. Chest CT scan was done after 2 and 6months for assessment of pleural effusion and pleural thickening. ResultsPatients with tuberculous pleural effusion had higher pleural effusion ADA levels (mean±SD 68.51±24.06) than those with malignant pleural effusion (mean±SD 25.47±12.09) or transudative pleural effusion (mean±SD 16.58±2.93) and these levels had highly a significant difference (P-value <0.001). Also, there was a significant difference (P-value <0.05) between levels of ADA in malignant and transudative pleural effusion. Using a cut-off point of the pleural fluid ADA (30.49IU/L) with AUC of 96.7 (sensitivity 96.7%, specificity 84%, NPV 88%, PPV 95% and accuracy 91%) discrimination between tuberculous and other causes of pleural effusion occurred. Regarding the pleural thickening, after 2months of ttt, in group I, 3 cases developed pleural thickening, while in group II, 9 cases developed thickening. After 6months, there was one case of pleural thickening in group I, while in group II, 5 cases developed pleural thickening. And there was a significant difference (P value <0.05) between both groups, after 2 and 6months of treatment. ConclusionsThoracentesis is very important in the diagnosis of TPE either through diagnostic thoracentesis by measuring fluid markers such as ADA or therapeutic thoracentesis which is not only important for relieving dyspnea but also in preventing occurrence of pleural thickening that complicated cases of TPE.

Factors Influencing Pleural Adenosine Deaminase Level in Patients With Tuberculous Pleurisy

BackgroundAdenosine deaminase (ADA) activity is useful for diagnosing tuberculous (TB) pleurisy in regions with a high prevalence of tuberculosis. However, some cases of TB pleural effusion show decreased ADA activity. Therefore, we evaluated factors influencing pleural ADA levels in patients with TB pleurisy. MethodsWe retrospectively evaluated 182 patients with TB pleural effusion who were admitted to Gyeongsang National University Hospital from January 2004 to September 2008. Patients were dichotomized into 2 groups: a low-ADA (<40 IU/L) group (n = 22) and a high-ADA (≥40 IU/L) group (n = 160). Age, sex, ADA level of pleural effusion, smoking status, history of tuberculosis and comorbid diseases were evaluated in each group. ResultsThe median age of the patients was 50.5 years, with a male to female ratio of 1.72:1. Patients with a low-ADA level were significantly older than those with a high ADA level (66.9 ± 12.0 versus 49.4 ± 21.2 years, P < 0.001). A history of tuberculosis and hypertension was more common in the low-ADA group than in the high-ADA group (31.8% versus 15.0%, P = 0.049 and 36.4% versus 16.9%, P = 0.03, respectively). A multivariate analysis revealed that older age and current smoking were predictive of TB pleurisy with a low ADA level (odds ratios, 1.053 and 4.848; P = 0.002 and 0.028, respectively). ConclusionsPhysicians should be careful when interpreting pleural ADA levels in elderly patients and/or current smokers for the diagnosis of TB pleurisy.

SAT0346 Anti-Drug Antibodies as A Predictor for the Discontinuation of Anti-TNF Agents in Patients with Spondyloarthrtis

BackgroundTumor necrosis factor (TNF) blocking agent has shown to be effective in patients with axial spondyloarthritis (SpA) including ankylosing spondylitis (AS) as up to 60-70%. However, the other 30-40% of...

FRI0269 The Utility of the Mechanistic Model in Inflammatory Arthropaties with Secondary Clinical Failure to Adalimumab, but not to Etanercept

BackgroundThe development of biological therapies which block the tumor necrosis factor alfa (TNFα) has revolutionized the treatment of various inflammatory diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS) and...

English

BACKGROUND: Tuberculosis is one of the most widely prevalent infectious disease causing high morbidity and mortality in humans. Serum ADA is a low cost test with proven diagnostic significance. AIMS AND OBJECTIVES: To assess change of Serum ADA levels as an indicator of response to the treatment, the prognostic value of ADA levels in childhood tuberculosis and its role in early detection of drug resistance or treatment failure if any. MATERIALS AND METHODS: A prospective analytical study (n=59) was conducted in Niloufer hospital from July 2012 to September 2013. A total of 32 patients were enrolled in tuberculous meningitis group and 27 in pulmonary tuberculosis group. Blood samples were drawn at the time of diagnosis, 1 month and 2 months after starting treatment. ADA levels were measured using Guisti’s method. Data collected was analyzed using SPSS 16 software. RESULTS: Mean Serum ADA levels on Day 1, 1 month, 2nd month samples were [46.97±11.00], [31.51± 6.27], [21.67± 4.00] and [32.31± 5.90], [24.03± 4.38], [18.43± 2.76] in Pulmonary Koch’s and TBM group respectively. Serum ADA levels showed a significant decrease (p < 0.000) after the initiation of treatment. Sex, age and nutritional status as measured by weight for age did not have a significant effect on Serum ADA value. There was a significant difference between mean ADA levels in the pulmonary tuberculosis group and TBM group but age was confounding factor. In the TBM group, 5 children who succumbed to the disease had a significantly (p = 0.016) lower Serum ADA levels (mean = 22.08) when compared to other children who have not succumbed to the disease. The relative risk of a TBM child dying with the disease was calculated to be 8.9 if the Serum ADA levels were less than 22IU/dl. CONCLUSIONS: There was a significant sequential decrease in Serum ADA levels in tuberculosis patients with treatment and these were not influenced by age, sex and nutritional status. A low level of Serum ADA in TBM is a significant negative prognostic indicator.

Tu1201 Large Variation in Infliximab Trough Levels Is Associated With Disease Activity in Paediatric Inflammatory Bowel Disease

prospectively collected by questionnaire and from the treating doctor. Results: 40 mother-baby pairs have been tested (20 IFX and 20 ADA). Drug was ceased prior to gestational week (GW) 30 in 16 (40%) women without disease flares. In them, mean serum concentrations were 1.78 mg/ml (IFX) and 0.15 mg/ml (ADA), and the cord blood level at delivery was <3mg/ml in 12/16 (75%). There was a strong correlation between cord blood and maternal levels at delivery (IFX: Pearson’s r = 0.77, p < 0.0001; ADA: r = 0.753, p < 0.0001). An inverse correlation between duration since last exposure and maternal ATA levels at birth was found (IFX: r = 0.55, p = 0.01; v ADA: r = 0.48, p = 0.04). This was also the case for cord IFX levels at birth (r = 0.532, p = 0.02), but not for cord ADA levels at birth (r = 0.38, p = 0.12). Complete clearance of ATA was seen in 14/17 babies by 6 months and in this group 7 stopped ATA by week 30. To date there has been no detectable ATA levels by 9 months. One woman (2.5%) gave birth preterm (GW 34+1). No congenital malformations were detected and all babies are developing normally. Conclusions: Cord blood ATA levels were strongly correlated with maternal level at delivery. Maternal and neonatal ATA levels seem to be inversely correlated with the duration since last exposure. Maternal cessation of ATA prior to week 30 successfully reduced fetal exposure to drug in the majority of cases. Follow up will determine whether high neonatal levels have any negative consequences.

Evaluation of Adenosine Deaminase (ADA) Activity for Diagnosis of Tubercular Pleural Effusion

To find out a sensitive and specific marker for early diagnosis of tubercular pleural effusion, this cross sectional study was carried out in the of National Institute of Diseases of the Chest and Hospital (NIDCH), Dhaka. One hundred and three pleural effusion cases were enrolled in the study. Out of the 103 cases, 62 were tubercular pleural effusion cases and 49 were nontubercular cases. Among the nontubercular cases, 30 cases were due to malignancy, 8 were due to pneumonia and rest 3 cases were due to nephrotic syndrome, congestive cardiac failure and rheumatoid arthritis. Considering 40 U/L as a cut off value for ADA level, the test result was positive in 58 out of 62 patients of tuberculosis indicating sensitivity of the test as 94%; however, among 41 non-tuberculous patients, 5 presented ADA activity level more than 40U/L, which lowers the specificity of the test to 88%. ADA levels were significantly higher in tuberculous than in nontuberculous cases (p value &lt;0.001). It may be concluded that ADA levels are significantly high in patients with tuberculous pleural effusion compared to that in non-tubercular group. Sensitivity (94%) and specificity (88%) of the test in tuberculous pleural effusions are very high, when cut off value set at 40U/L. The result indicated that the analysis of ADA levels in pleural effusion constitute a very useful marker for the diagnosis of tubercular pleural effusion (TPE) which, in addition, can be made quickly in a noninvasive way. DOI: http://dx.doi.org/10.3329/bjmb.v6i2.17642 Bangladesh J Med Biochem 2013; 6(2): 40-48

Pleural fluid LDH-Cholesterol and ADA levels: Useful biochemical markers in comparision to Light and #8217;s criteria for more rapid and accurate evaluation of pleural effusion

Background: Early and decisive evidence of pleural effusion as transudative or exudative nature is of considerable importance for further diagnostic procedure and therapeutic implication. Aims & Objective: To evaluate the utility of PF LDH-Cholesterol including Triglycerides level and ADA levels and comparing it with Light’s criteria for rapid and accurate evaluation of Pleural effusion mainly exudates. Materials and Methods: Total of 100 cases of Pleural effusion studied from July 2011 to September 2012. All the cases were evaluated by clinical, biochemical, cytological analysis of pleural effusion to diagnose underlying cause and different methods were compared for its diagnostic value, its sensitivity and specificity. Results: Out of all the effusions, 94 were exudative and 6 were transudative in nature. The commonest cause of effusion was tuberculous (58 cases) followed by malignancy (24 cases). 62 patients showed ratio of pleural fluid and serum protein 60 mg/dl. 86.2% of patients with TB and 79.16% of malignancy patients had pleural fluid cholesterol levels > 60 mg/dl with pleural fluid to serum cholesterol ratio of >0.4. Pleural fluid triglyceride levels were >40 mg/dl in 50% of the patients. Pleural fluid LDH levels were 135 ± 37 in transudative effusion while it was 676 ± 414, 559 ± 225 and 678 ± 513 in exudative, tuberculous and malignant effusion respectively. Similarly ratio of pleural fluid to serum LDH was <0.6 in transudative while it was 2.68 ± 3.27, 1.93 ± 1.15 and 1.61 ± 1.13 in exudative, tuberculous and malignant effusion respectively. Pleural fluid ADA levels were 20 ± 17, 53.5 ± 43, 65.48 ± 39.9 and 24.29 ± 24.72 in transudative, exudative, tuberculous and malignant effusions respectively. It was found that the specificity of separating transudate and exudates and positive predictive value was 100% with light’s criteria, pleural fluid LDH levels and pleural fluid to serum LDH ratio. Sensitivity and specificity of ADA in tuberculous effusion is 79.31% and 76.16% respectively. Conclusion: In clinical setting Light’s criteria generally distinguish the exudative from transudative pleural effusion. Current study supports other studies in stating that the alternative criteria like PF LDH-Cholesterol and ADA levels must be considered as a good alternative.

Role of Nucleic Acid Amplification Tests (NAATs) in Tuberculous Pleural Effusion: Where It Fits In Routine Diagnostic Workup?

Background: Commonest cause of pleural effusion in India is tuberculosis (TB) and poses a diagnostic difficulty because of the low sensitivity of culture technique. Methods: Prospective study conducted during Jan 2012 to Sept. 2013 with an objective to find role of Nucleic acid amplification tests (NAATs) in tuberculous pleural effusion. We also observed comparison of NAATs i.e. MTB DNA PCR with other conventional diagnostic techniques like pleural fluid biochemistry, ADA (adenosine deaminase level), cytology and culture for mycobacterium tuberculosis, included 100 cases with signs, symptoms, history and radiological features suggestive of tuberculous pleural effusion. All the cases were subjected to pleural fluid analysis, smear for AFB, ADA, cytology, AFB culture on LJ media & MTB DNA PCR. Statistical analysis was done by using t-test and chi-test. Results: Out of total 100 cases with pleural effusion, 09% cases were sputum positive for AFB, 3% pleural fluid samples positive for AFB, 28% were culture positive, 74% were DNA PCR positive, and 85% cases had ADA >40 units/liter, 87% cases had a LN Ratio greater than 0.75. Sensitivity, specificity, PPV & NPV of PCR for MTB was observed 92.86%, 33.33%, 35.13% & 92.30% respectively (p 0.4). In PCR negative cases; there was statistically significant association between ADA levels in pleural fluid culture for MTB positive and negative results. (P 40 units/liter, DNA PCR and LN ratio >0.75 gave a positive diagnostic yield in 98% of cases, 2% with diagnostic dilemma were diagnosed by pleural biopsy. ATT response was observed in 78% cases in 2 weeks, 98% cases in 4 weeks and 100% cases at the end of 6 weeks. Conclusion: In cases with exudative pleural effusion with Lymphocyte in pleural fluid >50% and L/N ratio>0.75 with ADA <40 units, MTB DNA PCR (NAATs) will be very useful in confirming tuberculosis as a cause for pleural effusion. Results of NAATs in this situation are very useful, sensitive, less time consuming and comparable to pleural fluid culture. Hence we recommend MTB DNA PCR in these cases.