| 92311. |
- Svärd, Anna, et al.
(författare)
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Presence and immunoreactivity of Aggregatibacter actinomycetemcomitans in rheumatoid arthritis
- 2024
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Ingår i: Pathogens. - : MDPI. - 2076-0817. ; 13:5, s. 368-368
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Tidskriftsartikel (refereegranskat)abstract
- The presence of periodontal pathogens is associated with an increased prevalence of rheumatoid arthritis (RA). The systemic antibody response to epitopes of these bacteria is often used asa proxy to study correlations between bacteria and RA. The primary aim of the present study is toexamine the correlation between the presence of Aggregatibacter actinomycetemcomitans (Aa) in theoral cavity and serum antibodies against the leukotoxin (LtxA) produced by this bacterium. Thesalivary presence of Aa was analyzed with quantitative PCR and serum LtxA ab in a cell culturebased neutralization assay. The analyses were performed on samples from a well-characterized RAcohort (n = 189) and a reference population of blood donors (n = 101). Salivary Aa was present in15% of the RA patients and 6% of the blood donors. LtxA ab were detected in 19% of RA-sera andin 16% of sera from blood donors. The correlation between salivary Aa and serum LtxA ab wassurprisingly low (rho = 0.55 [95% CI: 0.40, 0.68]). The presence of salivary Aa showed no significantassociation with any of the RA-associated parameters documented in the cohort. A limitation of thepresent study is the relatively low number of individuals with detectable concentrations of Aa insaliva. Moreover, in the comparison of detectable Aa prevalence between RA patients and blooddonors, we assumed that the two groups were equivalent in other Aa prognostic factors. These limitations must be taken into consideration when the result from the study is interpreted. We concludethat a systemic immune response to Aa LtxA does not fully reflect the prevalence of Aa in saliva. Inaddition, the association between RA-associated parameters and the presence of Aa was negligiblein the present RA cohort.
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| 92312. |
- Svärd, Anna, et al.
(författare)
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Presence and utility of IgA-class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis : the Swedish TIRA project
- 2008
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe present study was carried out to assess whether IgA-class antibodies against cyclic citrullinated peptides (IgA anti-CCP) in recent-onset rheumatoid arthritis add diagnostic and/or prognostic information to IgG anti-CCP analysis.MethodsSerum samples were obtained from 228 patients with recent-onset (<12 months) rheumatoid arthritis at the time of inclusion in the Swedish TIRA cohort (Swedish Early Intervention in Rheumatoid Arthritis). Sera from 72 of these patients were also available at the 3-year follow-up. Disease activity and functional ability measures (erythrocyte sedimentation rate, serum C-reactive protein, 28-joint count Disease Activity Score, physician's assessment of disease activity, and the Swedish version of the Health Assessment Questionnaire) were registered at inclusion and at regular follow-ups during 3 years. An IgA anti-CCP assay was developed based on the commercially available IgG-specific enzyme immunoassay from EuroDiagnostica (Arnhem, the Netherlands), replacing the detection antibody by an anti-human-IgA antibody. A positive IgA anti-CCP test was defined by the 99th percentile among healthy blood donors.ResultsAt baseline, a positive IgA anti-CCP test was observed in 29% of the patient sera, all of which also tested positive for IgG anti-CCP at a higher average level than sera containing IgG anti-CCP alone. The IgA anti-CCP-positive patients had significantly higher disease activity over time compared with the IgA anti-CCP-negative patients. After considering the IgG anti-CCP level, the disease activity also tended to be higher in the IgA anti-CCP-positive cases – although this difference did not reach statistical significance. The proportion of IgA anti-CCP-positive patients was significantly larger among smokers than among nonsmokers.ConclusionAnti-CCP antibodies of the IgA class were found in about one-third of patients with recent-onset rheumatoid arthritis, all of whom also had IgG anti-CCP. The occurrence of IgA-class antibodies was associated with smoking, and IgA anti-CCP-positive patients had a more severe disease course over 3 years compared with IgA anti-CCP-negative cases. Although IgA anti-CCP analysis does not seem to offer any diagnostic information in addition to IgG anti-CCP analysis, further efforts are justified to investigate the prognostic implications.
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| 92313. |
- Svärd, Anna, 1985-, et al.
(författare)
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Protein-Functionalized Gold Nanoparticles as Refractometric Nanoplasmonic Sensors for the Detection of Proteolytic Activity of Porphyromonas gingivalis
- 2020
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Ingår i: ACS Applied Nano Materials. - : American Chemical Society. - 2574-0970. ; 3:10, s. 9822-9830
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Tidskriftsartikel (refereegranskat)abstract
- Periodontitis is an inflammatory oral disease that affects a large part of the adult population, causing significant costs and suffering. The key pathogen, Porphyromonas gingivalis, secretes gingipains, which are highly destructive proteases and the most important virulence factors in the pathogenesis of the disease. Currently, periodontitis is diagnosed mainly by mechanical manual probing and radiography, often when the disease has already progressed significantly. The possibilities of detecting gingipain activity in gingival fluid could enable early-stage diagnosis and facilitate treatment. Here, we describe a sensitive nanoparticle-based nanoplasmonic biosensor for the detection of the proteolytic activity of gingipains. Gold nanoparticles (AuNPs) were self-assembled as a submonolayer in multiwell plates and further modified with casein or IgG. The proteolytic degradation of the protein coating was tracked by monitoring the shift in the localized surface plasmon resonance (LSPR) peak position. The sensor performance was investigated using model systems with trypsin and purified gingipains (subtypes Kgp and RgpB) and further validated using supernatants from cultures of P. gingivalis. Proteolytic degradation by proteases in buffer results in a concentration- and time-dependent blueshift of the LSPR band of about 1-2 nm when using casein as a substrate. In bacterial supernatants, the degradation of the protein coating resulted in unspecific binding of proteins present in the complex sample matrix to the nanoparticles, which instead triggered a redshift of about 2 nm of the LSPR band. A significant LSPR shift was seen only in samples with gingipain activity. The sensor showed a limit of detection < 0.1 mu g/mL (4.3 nM), which is well below gingipain concentrations detected in severe chronic periodontitis cases (similar to 50 mu g/mL). This work shows the possibility of developing cost-effective nanoparticle-based biosensors for rapid detection of protease activity for chair-side periodontal diagnostics.
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| 92314. |
- Svärd, Anna, et al.
(författare)
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Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis
- 2013
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Ingår i: Immunobiology. - : Elsevier. - 0171-2985 .- 1878-3279. ; 218:2, s. 232-237
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Tidskriftsartikel (refereegranskat)abstract
- Circulating IgG anti-cyclic citrullinated peptide antibodies (CCP) are highly specific for rheumatoid arthritis (RA) and prognostic of poor outcome. Serum IgA anti-CCP occurs in a subset of IgG-positive cases and relates to still more aggressive disease. Mucosal IgA-class antibodies, however, are generally associated with anti-inflammatory actions and systemic tolerance induction. In the present study, unstimulated salivary samples from 63 patients with established RA and 20 healthy persons were analysed by enzyme-linked immunoassay for the presence of IgA anti-CCP antibodies. To ensure antigen specificity, IgA-reactivity with the corresponding uncitrullinated antigen, cyclic arginine peptide (CAP), was analysed and anti-CCP/anti-CAP ratios calculated. Retrospective data regarding disease activity and radiological outcome were achieved via medical records. Salivary IgA anti-CCP was found in 14/63 (22%) patients and one (5%) control (positive test = anti-CCP/anti-CAP ratio andgt; 1.5). Salivary IgA reactivity was dose-dependently inhibited by pre-incubation with soluble CCP to a degree strongly correlating with anti-CCP/anti-CAP ratio. In salivary IgA anti-CCP positive patients, joint erosions within 6 years of diagnosis was significantly lower (p = 0.043), and at the time for diagnosis there was a trend towards lower erythrocyte sedimentation rate (p = 0.071) and C-reactive protein (p = 0.085). Contrasting to circulating IgG and IgA anti-CCP, our results imply that salivary IgA antibodies may be associated with a less severe outcome of RA. Hypothetically, this relates to an anti-inflammatory and protective immunomodulating role of secretory IgA-class autoantibodies against citrullinated antigens presented at mucosal surfaces.
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| 92315. |
- Svärd, Anna, et al.
(författare)
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Secretory antibodies to citrullinated peptides in plasma and saliva from rheumatoid arthritis patients and their unaffected first-degree relatives
- 2020
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Ingår i: Clinical and Experimental Immunology. - : WILEY. - 0009-9104 .- 1365-2249. ; 199:2, s. 143-149
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (< 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.
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| 92316. |
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| 92317. |
- Svärd, Carl, 1981-, et al.
(författare)
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A Data-Driven and Probabilistic Approach to Residual Evaluation for Fault Diagnosis
- 2011
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Ingår i: 50th IEEE Conference on Decision and Control and European Control Conference (CDC-ECC), 2011. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781612848006 - 9781612848013 - 9781467304573 - 9781612847993 ; , s. 95-102
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Konferensbidrag (refereegranskat)abstract
- An important step in fault detection and isolation is residual evaluation where residuals, signals ideally zero in the no-fault case, are evaluated with the aim to detect changes in their behavior caused by faults. Generally, residuals deviate from zero even in the no-fault case and their probability distributions exhibit non-stationary features due to, e.g., modeling errors, measurement noise, and different operating conditions. To handle these issues, this paper proposes a data-driven approach to residual evaluation based on an explicit comparison of the residual distribution estimated on-line and a no-fault distribution, estimated off-line using training data. The comparison is done within the framework of statistical hypothesis testing. With the Generalized Likelihood Ratio test statistic as starting point, a more powerful and computational efficient test statistic is derived by a properly chosen approximation to one of the emerging likelihood maximization problems. The proposed approach is evaluated with measurement data on a residual for diagnosis of the gas-flow system of a Scania truck diesel engine. The proposed test statistic performs well, small faults can for example be reliable detected in cases where regular methods based on constant thresholding fail.
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| 92318. |
- Svärd, Carl, et al.
(författare)
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A Greedy Approach for Selection of Residual Generators
- 2011
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Konferensbidrag (refereegranskat)abstract
- This paper considers the problem of selecting a set of residual generators, fulfilling requirements in terms of fault isolability and minimal cardinality, for inclusion in a model-based FDI-system. Two novel algorithms for solving the selection problem are proposed. The first one provides an exact solution fulfilling both requirements and is suitable for small problems. The second one, which is the main contribution and suitable for large problems, relaxes the minimal cardinality requirement and provides an approximate solution by means of a greedy heuristic. Both algorithms take the realizability properties of the considered residual generation method into account, but are general in the sense that they support any computerized residual generation method. In a case study the greedy algorithm is applied to the problem of finding a suitable set of residual generators for detection and isolation of faults in a complex truck diesel engine system. In this study a prior known sequential residual generation method is considered.
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| 92319. |
- Svärd, Carl, et al.
(författare)
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A Mixed Causality Approach to Residual Generation Utilizing Equation System Solvers and Differential-Algebraic Equation Theory
- 2008
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Ingår i: Proceedings of the 19th International Workshop on Principles of Diagnosis DX'08. - Linköping : Department of Electrical Engineering. ; , s. 181-188
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Konferensbidrag (refereegranskat)abstract
- The FDI approach to model-based diagnosis is considered. We present a method for residual generation that combines integral and derivative causality, and also utilizes equation system solvers and theory of differential-algebraic equation systems. To achieve this, a framework for computation of variables from sets of dependent differential and/or algebraic equations is introduced. The proposed method is applied to a model of the gas flow in an automotive diesel engine. The application clearly shows the benefit of using a mixed causality approach for residual generation compared with solely integral or derivative causality.
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| 92320. |
- Svärd, Carl, 1981-, et al.
(författare)
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An Observer-Based Residual Generation Method for Linear Differential-Algebraic Equation Systems
- 2009
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Ingår i: European Journal of Control. - 0947-3580 .- 1435-5671.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Residual generation for linear differential-algebraic systems is considered. A new systematic method for observer-based residual generation is presented. The proposed design method places no restrictions on the system to be diagnosed. If the fault of interest can be detected in the system, the output from the design method is a residual generator in state-space form that is sensitive to the fault of interest. The method is iterative and relies only on constant matrix operations such as multiplications, null-space calculations and equivalence transformations, and thereby straightforward to implement. An illustrative numerical example is included, where the design method is applied to a nonobservable model of a robot manipulator.
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