Lab-on-a-chip: Emerging analytical platforms for immune-mediated diseases

Miniaturization of analytical procedures has a significant impact on diagnostic testing since it provides several advantages such as: reduced sample and reagent consumption, shorter analysis time and less sample handling. Lab-on-a-chip (LoC), usually silicon, glass, or silicon-glass, or polymer disposable cartridges, which are produced using techniques inherited from the microelectronics industry, could perform and integrate the operations needed to carry out biochemical analysis through the mechanical realization of a dedicated instrument.Analytical devices based on miniaturized platforms like LoC may provide an important contribution to the diagnosis of high prevalence and rare diseases. In this paper we review some of the uses of Lab-on-a-chip in the clinical diagnostics of immune-mediated diseases and we provide an overview of how specific applications of these technologies could improve and simplify several complex diagnostic procedures.     

Striatal hand in Parkinson’s disease: the re-evaluation of an old clinical sign

Among postural abnormalities in Parkinson’s disease (PD), striatal hand (SH) is a particularly underexplored phenomenon. It leads to extreme abnormalities of hand posture, causing altered dexterity, pain and disfigurement. In our study, three blinded investigators examined several pictures of the hands of individuals with PD (N = 40) and controls (N = 15). The investigators quantified postural alterations using the Striatal Hand Score. Demographic and clinical data were also collected. As no differences were detected among investigators agreement, a final Hand Score (HS, range 0–4) was obtained for each hand. The Striatal Hand Score in both the left and right hand was significantly different in PD compared to controls (p < 0.001 for both left and right hand). Striatal hand was significantly worse on the side of PD onset, and on the side with greater PD symptomatology. The finding of a striatal hand was 100 % specific for a diagnosis of PD. Nine PD subjects were evaluated both on and off medication, and dopaminergic treatment did not significantly change the Striatal Hand Score. Our findings suggest that in patients without any explanation for hand deformities other than PD, striatal hand occurs very often, and is highly specific for the side of worst PD involvement. We recommend including an evaluation for SH as part of routine practice. This study emphasizes the importance of a careful observation of the patient in order to improve diagnostic accuracy.     

Atrial natriuretic factor in cardiogenic shock, in hypovolemic shock and in the bradycardia-hypotension syndrome following acute myocardial infarction

The aim of this paper was to study plasma atrial natriuretic factor, renin activity, aldosterone and antidiuretic hormone in low-output heart failure syndromes such as cardiogenic shock, hypovolemic shock and hypotension with bradycardia syndrome. A total of 30 patients were investigated: 10 with cardiogenic shock due to acute myocardial infarction of the anterior wall (systolic and diastolic blood pressure 56.0 +/- 3.7/40.5 +/- 2.0 mmHg; heart rate 119.7 +/- 1.2 beats/min; central venous pressure 16.2 +/- 0.6 cmH2O) (I group), 10 with hypovolemic shock induced by melena in peptic ulcer (systolic and diastolic blood pressure 74.5 +/- 1.5/57.5 +/- 1.7 mmHg; heart rate 111.0 +/- 1.4; central venous pressure 6.3 +/- 0.5 cmH2O) (II group), 10 with hypotension with bradycardia syndrome which occurred in patients during acute myocardial infarction of the inferior wall (systolic and diastolic blood pressure 71.9 +/- 2.0/58.0 +/- 2.6 mmHg; heart rate 52.0 +/- 2.2 beats/min; central venous pressure 4.6 +/- 0.4 cmH2O) (III group). Plasma atrial natriuretic factor values were measured using radioimmunoassay after chromatographic pre-extraction; plasma renin activity, aldosterone and antidiuretic hormone values were calculated using radioimmunoassay. Circulating atrial natriuretic factor was significantly (p less than 0.01) higher in patients with cardiogenic shock (102.4 +/- 7.4 pg/ml) than in healthy volunteers (8.4 +/- 0.3 pg/ml). In the former there was a positive correlation between atrial natriuretic factor and central venous pressure values. Atrial natriuretic factor and central venous pressure values in the IInd and IIIrd groups of patients were in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)     

C-C chemokine receptor 2 and sarcoidosis: association with Lofgren's syndrome

Sarcoidosis is thought to result from the interaction between an unknown environmental antigenic trigger and the host's genetic susceptibility. We hypothesized that sarcoidosis, or one of the disease subsets, could be associated with single nucleotide polymorphisms of C-C chemokine receptor 2 (CCR2) gene. Eight single-nucleotide polymorphisms in CCR2 were studied in a total of 304 Dutch individuals (90 non-L?fgren sarcoidosis, 47 L?fgren's syndrome, 167 control subjects). From the investigated CCR2 polymorphisms, nine haplotypes were deduced (haplotypes 1-9). In patients with L?fgren's syndrome, a strongly significant increase in the frequency of CCR2-haplotype 2, which includes four unique alleles (A at nucleotide position -6752, A at 3,000, T at 3,547, and T at 4,385), was observed compared with control subjects (74% vs. 38% respectively, p < 0.0001), whereas no difference was found between non-L?fgren sarcoidosis and control subjects (both 38%). The association between CCR2-haplotype 2 carriage frequency and L?fgren's syndrome (odds ratio, 4.4; p < 0.0001) remained significant after adjustment for human leukocyte antigen haplotype DRB1*0301-DQB1*0201 (odds ratio, 11.5; p < 0.0001) and female sex (odds ratio, 3.2; p = 0.003), two known risk factors for L?fgren's syndrome. In conclusion, this report describes a strong association between CCR2-haplotype 2 and L?fgren's syndrome. Further studies are needed to understand the molecular mechanisms underlying this association.     

IL-5 promotes induction of antigen-specific CD4+CD25+ T regulatory cells that suppress autoimmunity

Immune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Rα chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Rα and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il-5rα. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5rα and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity.     

Contact Patch to Rim Distance Predicts Metal Ion Levels in Hip Resurfacing

Background

Component design, size, acetabular orientation, patient gender, and activity level have been suggested as factors leading to elevated metal ion concentrations after-on-metal hip resurfacing arthroplasty (MMHRA). The calculation of the contact patch to rim (CPR) distance integrates component size, design, and acetabular orientation and may be a good predictor of elevated metal ion levels.

Questions/purposes

We evaluated the effects and the predictive value of the CPR distance on serum cobalt (CoS) and chromium (CrS) ion levels.

Methods

We retrospectively studied 182 patients with Conserve Plus MMHRAs at a minimum of 12 months after surgery (median, 57 months; range, 12–165 months). CoS and CrS levels were analyzed using inductively-coupled plasma mass spectrometry. Multiple logistic regression was performed to determine which if any of the factors related to serum ion levels.

Results

Patients with CPR distances of 10 mm or less had a 37-fold increased risk of having elevated CoS of 7 μg/L or higher. Similarly, these patients had an 11-fold increased risk of having elevated CrS of 7 μg/L or higher. Sex and University of California Los Angeles activity scores did not influence the postoperative CoS and CrS levels. The negative predictive value for CPR distance less than 10 mm was 99.3% for CoS greater than 7 μg/L and 98.0% for CrS greater than 7 μg/L.

Conclusions

Our observations suggest the CPR distance would be a useful indicator to determine which patients are at risk for elevated ion levels. Patients with CPR distances greater than 10 mm need not be monitored unless they become symptomatic.