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1.
Proc Biol Sci ; 288(1946): 20210108, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33653139

RESUMO

As an outcome of natural selection, animals are probably adapted to select territories economically by maximizing benefits and minimizing costs of territory ownership. Theory and empirical precedent indicate that a primary benefit of many territories is exclusive access to food resources, and primary costs of defending and using space are associated with competition, travel and mortality risk. A recently developed mechanistic model for economical territory selection provided numerous empirically testable predictions. We tested these predictions using location data from grey wolves (Canis lupus) in Montana, USA. As predicted, territories were smaller in areas with greater densities of prey, competitors and low-use roads, and for groups of greater size. Territory size increased before decreasing curvilinearly with greater terrain ruggedness and harvest mortalities. Our study provides evidence for the economical selection of territories as a causal mechanism underlying ecological patterns observed in a cooperative carnivore. Results demonstrate how a wide range of environmental and social conditions will influence economical behaviour and resulting space use. We expect similar responses would be observed in numerous territorial species. A mechanistic approach enables understanding how and why animals select particular territories. This knowledge can be used to enhance conservation efforts and more successfully predict effects of conservation actions.

2.
Semin Arthritis Rheum ; 51(2): 464-468, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33774593

RESUMO

BACKGROUND/PURPOSE: A universally accepted definition of axial psoriatic arthritis (axPsA) is lacking. We aimed to 1) assess the presence of axial involvement as defined by "at least unilateral grade 2 sacroiliitis (Uni2SI)" and 2) assess the radiographic progression of Uni2SI and identify risk factors for progression. METHODS: PsA patients participating in a prospective observational cohort were classified according to their highest sacroiliitis grade. The baseline features of patients with Uni2SI were compared to patients meeting the radiographic criteria of the modified New York Ankylosing Spondylitis (mNY AS) criteria. Risk factors were examined for progression from Uni2SI in a sub-group of patients with >1 follow-up radiographs. Logistic regression and a survival analysis were carried out and identified risk factors associated with radiographic mNY AS compared to Uni2SI. RESULTS: Axial disease defined as ≥Uni2SI was detected in 612/1354 patients (45%). mNY AS sacroiliitis was observed in 477 patients (35%). Radiographic progression of Uni2SI was assessed in 154 patients, 80 (52%) progressed to mNY AS criteria within 5.5 years. At baseline, progressors were diagnosed at a younger age (35.6 vs. 38.9, p = 0.05), had less degenerative disc disease (OR = 0.47, p = 0.02), worse peripheral radiographic damage (OR=1.02, p = 0.03) and worse psoriasis (OR = 1.09, p = 0.01) compared to non-progressors. Patients with an elevated erythrocyte sedimentation rate were more likely to progress (HR = 1.83, p = 0.02), while patients with longer disease duration were less likely to progress (HR = 0.95, p = 0.02). CONCLUSION: The radiographic mNY AS criteria appear to be suitable for defining axial PsA according to radiographs. MRI definitions are needed as well for the most appropriate definition of axial PsA.

4.
Rheum Dis Clin North Am ; 47(2): 197-213, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33781490

RESUMO

Inflammatory back pain is characteristic of spondyloarthritis (SpA); however, this pain may not respond to treatment with NSAIDs or biologics. Pain is multifactorial and a combination of mechanical and inflammatory factors. A growing body of literature examines the impact of emotions on pain in SpA; many patients with this condition suffer from depression and fibromyalgia. Advanced imaging techniques can investigate the interplay of various brain networks in pain perception. Animal models have helped understand the interplay between the immune and nervous systems in pain generation and have highlighted differences in pain perception between the sexes.

5.
Semin Immunopathol ; 43(2): 255-264, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33608820

RESUMO

Spondyloarthritis (SpA) is a chronic inflammatory disorder with complex etiology and pathogenesis. Its pathogenesis likely involves a combination of different factors. These factors include host genetics, environmental triggers, and immune and microbiota dysregulation. One of the strongest genetic associations with SpA is HLA-B27, implicating the involvement of cytotoxic T lymphocytes (CTLs) in SpA pathogenesis. Despite this discovery dating back decades ago, the CTL compartment that underlies SpA inflammation has yet to be fully defined until recently. Indeed, recent published studies support a significant role that CTLs play in contributing to chronic joint inflammation, which is a hallmark of SpA pathology. In this review chapter, we discuss emerging evidence that supports a newfound role of CTLs in SpA pathogenesis. This emerging evidence includes enrichment of CTL-related genes from genome-wide association studies, overrepresentation of pathogenic synovial CTL phenotype, clonal expansion, and immune dysregulation of CTLs. The discoveries of this mounting evidence suggest that CTL homeostasis is altered, and a disrupted adaptive immunity underlies the chronic inflammatory features seen in SpA pathology.

6.
Semin Immunopathol ; 43(2): 173-192, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33625549

RESUMO

The strong genetic and clinical overlaps between spondyloarthritis (SpA) and inflammatory bowel disease (IBD) have placed much needed focus on the gut-joint axis of inflammation in SpA, leading to three key hypotheses that attempt to unravel this complex relationship. The arthritogenic peptide hypothesis and the aberrant cellular trafficking hypothesis have been put forth to rationalize the manner by which the innate and adaptive immune systems cooperate and converge during SpA pathogenesis. The bacterial dysbiosis hypothesis discusses how changes in the microbiome lead to architectural and immunological consequences in SpA. These theories are not mutually exclusive, but can provide an explanation as to why subclinical gut inflammation may sometimes precede joint inflammation in SpA patients, thereby implying a causal relationship. Such investigations will be important in informing therapeutic decisions which may be common to both SpA and IBD. However, these hypotheses can also offer insights for a coincident inflammatory relationship between the gut and the joint, particularly when assessing the immunological players involved. Insights from understanding how these systems might affect the gut and joint differently will be equally imperative to address where the therapeutic differences lie between the two diseases. Collectively, this knowledge has practical implications in predicting the likelihood of IBD development in SpA or presence of coincident SpA-IBD, uncovering novel therapeutic targets, and redesigning currently approved treatments. It is evident that a multidisciplinary approach between the rheumatology and gastroenterology fields cannot be ignored, when it comes to the care of SpA patients at risk of IBD or vice versa.

7.
Pain ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33044396

RESUMO

Men and women can exhibit different pain sensitivities and many chronic pain conditions are more prevalent in one sex. Although there is evidence of sex differences in the brain, it is not known whether there are sex differences in the organization of large-scale functional brain networks in chronic pain. Here, we used graph theory with modular analysis and machine-learning of resting-state (RS)-fMRI data from 220 participants; 155 healthy controls and 65 individuals with chronic low back pain due to ankylosing spondylitis (AS), a form of arthritis.We found an extensive overlap in the graph partitions with the major brain intrinsic systems (i.e., default mode, central, visual and sensorimotor modules), but also sex-specific network topological characteristics in healthy people and those with chronic pain. People with chronic pain exhibited higher cross-network connectivity, and sex-specific nodal graph properties changes (i.e., Hubs disruption), some of which were associated with the severity of the chronic pain condition. Females exhibited atypically higher functional segregation in the mid- and subgenual cingulate cortex and lower connectivity in the network with the default mode and fronto-parietal modules; whereas males exhibited stronger connectivity with the sensorimotor module. Classification models on nodal graph metrics could classify an individuals' sex and whether they have chronic pain with high accuracies (77-92%). These findings highlight the organizational abnormalities of RS-brain networks in people with chronic pain and provide a framework to consider sex-specific pain therapeutics.

8.
Pain ; 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32773597

RESUMO

The subgenual anterior cingulate cortex (sgACC) plays an important role in pain modulation. We previously demonstrated sex differences in sgACC functional connectivity (FC) in healthy individuals. Given that many chronic pain conditions show sex differences in prevalence, here we tested the hypothesis that people with chronic pain exhibit a sex-specific pattern of abnormal sgACC FC. We acquired resting-state functional magnetic resonance imaging data from 156 (82 W: 74 M) healthy participants and 38 (19 W: 19 M) people with chronic low back pain resulting from ankylosing spondylitis, a condition that predominantly affects men. We confirmed that there are sex differences in sgACC FC in our large cohort of healthy adults; women had greater sgACC FC with the precuneus, a key node of the default mode network, and men had greater sgACC FC with the posterior insula and the operculum. Next, we identified an interaction effect between sex and pain status (healthy/chronic pain) for sgACC FC. Within the chronic pain group, women had greater sgACC FC than men to the default mode and sensorimotor networks. Compared to healthy women, women with chronic pain also had greater sgACC FC to the precuneus and lower FC to the hippocampus and frontal regions. No differences in sgACC FC were seen in men with vs without chronic pain. Our findings indicate that abnormal sgACC circuitry is unique to women but not men with ankylosing spondylitis-related chronic pain. These sex differences may impact the benefit of therapeutics that target the sgACC for chronic pain.

9.
J Mammal ; 101(3): 684-696, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32665740

RESUMO

Swift foxes (Vulpes velox) are endemic to the Great Plains of North America, but were extirpated from the northern portion of their range by the mid-1900s. Despite several reintroductions to the Northern Great Plains, there remains a ~350 km range gap between the swift fox population along the Montana and Canada border and that in northeastern Wyoming and northwestern South Dakota. A better understanding of what resources swift foxes use along the Montana and Canada border region will assist managers to facilitate connectivity among populations. From 2016 to 2018, we estimated the home range size and evaluated resource use within the home ranges of 22 swift foxes equipped with Global Positioning System tracking collars in northeastern Montana. Swift fox home ranges in our study were some of the largest ever recorded, averaging (± SE) 42.0 km2 ± 4.7. Our results indicate that both environmental and anthropogenic factors influenced resource use. At the population level, resource use increased by 3.3% for every 5.0% increase in percent grasslands. Relative probability of use decreased by 7.9% and 7.4% for every kilometer away from unpaved roads and gas well sites, respectively, and decreased by 3.0% and 11.3% for every one-unit increase in topographic roughness and every 0.05 increase in normalized difference vegetation index (NDVI), respectively. Our study suggests that, to reestablish connectivity among swift fox populations in Montana, managers should aim to maintain large corridors of contiguous grasslands at a landscape scale, a process that likely will require having to work with multiple property owners.

10.
J Mammal ; 101(3): 790-803, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32665742

RESUMO

Climate change can have particularly severe consequences for high-elevation species that are well-adapted to long-lasting snow conditions within their habitats. One such species is the wolverine, Gulo gulo, with several studies showing a strong, year-round association of the species with the area defined by persistent spring snow cover. This bioclimatic niche also predicts successful dispersal paths for wolverines in the contiguous United States, where the species shows low levels of genetic exchange and low effective population size. Here, we assess the influence of additional climatic, vegetative, topographic, and anthropogenic, variables on wolverine genetic structure in this region using a multivariate, multiscale, landscape genetic approach. This approach allows us to detect landscape-genetic relationships both due to typical, small-scale genetic exchange within habitat, as well as exceptional, long-distance dispersal among habitats. Results suggest that a combination of snow depth, terrain ruggedness, and housing density, best predict gene flow in wolverines, and that the relative importance of variables is scale-dependent. Environmental variables (i.e., isolation-by-resistance, IBR) were responsible for 79% of the explained variation at small scales (i.e., up to ~230 km), and 65% at broad scales (i.e., beyond ~420 km). In contrast, a null model based on only space (i.e., isolation-by-distance, IBD) accounted only for 17% and 11% of the variation at small and broad scales, respectively. Snow depth was the most important variable for predicting genetic structures overall, and at small scales, where it contributed 43% to the variance explained. At broad spatial scales, housing density and terrain ruggedness were most important with contributions to explained variation of 55% and 25%, respectively. While the small-scale analysis most likely captures gene flow within typical wolverine habitat complexes, the broad-scale analysis reflects long-distance dispersal across areas not typically inhabited by wolverines. These findings help to refine our understanding of the processes shaping wolverine genetic structure, which is important for maintaining and improving functional connectivity among remaining wolverine populations.

11.
J Clin Invest ; 130(4): 1863-1878, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32149730

RESUMO

Spondyloarthritis (SpA) represents a family of inflammatory diseases of the spine and peripheral joints. Ankylosing spondylitis (AS) is the prototypic form of SpA in which progressive disease can lead to fusion of the spine. Therapeutically, knowledge of type 3 immunity has translated into the development of IL-23- and IL-17A-blocking antibodies for the treatment of SpA. Despite being able to provide symptomatic control, the current biologics do not prevent the fusion of joints in AS patients. Thus, there is an unmet need for disease-modifying drugs. Genetic studies have linked the Janus kinase TYK2 to AS. TYK2 is a mediator of type 3 immunity through intracellular signaling of IL-23. Here, we describe and characterize a potentially novel small-molecule inhibitor of TYK2 that blocked IL-23 signaling in vitro and inhibited disease progression in animal models of SpA. The effect of the inhibitor appears to be TYK2 specific, using TYK2-inactive mice, which further revealed a duality in the induction of IL-17A and IL-22 by IL-23. Specifically, IL-22 production was TYK2/JAK2/STAT3 dependent, while IL-17A was mostly JAK2 dependent. Finally, we examined the effects of AS-associated TYK2 SNPs on TYK2 expression and function and correlated them with AS disease progression. This work provides evidence that TYK2 inhibitors have great potential as an orally delivered therapeutic for SpA.

12.
Neuroimage Clin ; 26: 102241, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32203904

RESUMO

We previously identified alpha frequency slowing and beta attenuation in the dynamic pain connectome related to pain severity and interference in patients with multiple sclerosis-related neuropathic pain (NP). Here, we determined whether these abnormalities, are markers of aberrant temporal dynamics in non-neuropathic inflammatory pain (non-NP) or when NP is also suspected. We measured resting-state magnetoencephalography (MEG) spectral density in 45 people (17 females, 28 males) with chronic back pain due to ankylosing spondylitis (AS) and 38 age/sex matched healthy controls. We used painDETECT scores to divide the chronic pain group into those with only non-NP (NNP) and those who likely also had a component of NP in addition to their inflammatory pain. We also assessed pain severity, pain interference, and disease activity with the Brief Pain Inventory and Bath AS Disease Activity Index (BASDAI). We examined spectral power in the dynamic pain connectome, including nodes of the ascending nociceptive pathway (ANP), default mode (DMN), and salience networks (SN). Compared to the healthy controls, the AS patients exhibited increased theta power in the DMN and decreased low-gamma power in the DMN and ANP, but did not exhibit beta-band attenuation or peak-alpha slowing. The NNP patients were not different from HCs. Compared to both healthy controls and NNP, NP patients had increased alpha power in the ANP. Increased alpha power within the ANP was associated with reduced BASDAI in the NNP group, and increased pain in the mixed-NP group within the DMN, SN, and ANP. Thus, high theta and low gamma activity may be markers of chronic pain but high alpha-band activity may relate to particular features of neuropathic chronic pain.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32166872

RESUMO

OBJECTIVE: We sought to investigate the effectiveness and safety of dose reduction of tumour necrosis factor inhibitor (TNFi) therapy in the treatment of axial spondyloarthritis (axSpA), compared to usual care. METHODS: We searched CENTRAL, Embase, MEDLINE and trial registries. We screened, extracted data, and assessed risk of bias in duplicate. Data were pooled using random-effects models; subgroup analyses were performed for type of TNFi, prior TNFi exposure and follow-up duration. Outcomes of interest were Assessment in SpondyloArthritis international Society (ASAS) response and remission criteria, disease activity, relapse and safety. RESULTS: We included six randomized trials with 747 participants (442 AS and 305 nr-axSpA). Compared to standard dose, there were fewer ASAS40 (risk ratio [RR] 0.62, 95% confidence interval [CI] 0.49 - 0.78) and ASAS partial remission (RR 0.17, 95% CI 0.06 - 0.46) events with the reduced dose. There was a mean increase in the Bath Ankylosing Spondylitis Disease Activity Index score (mean difference [MD] 0.35, 95% CI 0.10 - 0.60), and no difference in C-reactive protein levels (MD 0.16, 95% CI -0.76 - 1.07) with the reduced dose. There were more disease flares/relapses (RR 1.73, 95% CI 1.32 - 2.27) with the reduced dose. There were no differences in infection rates (incidence rate ratio [IRR] 0.98, 95% CI 0.76 - 1.25) or injection/infusion reactions (IRR 0.71, 95% CI 0.42 - 1.19). CONCLUSION: Patients with axSpA may experience little to no clinical benefit from reduction of TNFi therapy. Maintaining the standard dose probably improves the sustained effect on disease activity and helps to prevent disease flare.

14.
Arthritis Res Ther ; 22(1): 51, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188494

RESUMO

BACKGROUND: Little is known about the mechanisms underlying the clinical overlap between gut inflammation and joint ankylosis, as exemplified by the concurrence of inflammatory bowel diseases (IBD) and ankylosing spondylitis (AS). As dysbiosis may serve as a common contributor, the anti-microbial pleiotropic factor lipocalin 2 could be a potential mediator due to its roles in inflammation and bone homeostasis. METHODS: Baseline colonic pathology was conducted in the ank/ank mouse model. Serum lipocalin 2 was analyzed by ELISA, in ank/ank mutants versus C3FeB6-A/Aw-jwt/wt, in patients with concurrent AS-IBD, AS alone, IBD alone, or mechanical back pain, and in healthy controls. In the ank/ank mouse model, the expression of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) was examined by real-time PCR. Intraperitoneal injection was done with the PPARγ agonist rosiglitazone or antagonist bisphenol A diglycidyl ether for four consecutive days. Serum levels of lipocalin 2 were examined on the sixth day. RESULTS: This study showed that the ank/ank mice with fully fused spines had concurrent colonic inflammation. By first using the ank/ank mouse model with progressive ankylosis and subclinical colonic inflammation, confirmed in patients with concurrent AS and IBD, elevated circulating lipocalin 2 levels were associated with the coexisting ankylosis and gut inflammation. The intracellular pathway of lipocalin 2 was further investigated with the ank/ank mouse model involving PPARγ. Colonic expression of PPARγ was negatively associated with the degree of gut inflammation. The PPARγ agonist rosiglitazone treatment significantly upregulated the serum levels of lipocalin 2, suggesting a potential regulatory role of PPARγ in the aberrant expression of lipocalin 2. CONCLUSIONS: In summary, lipocalin 2 modulated by PPARγ could be a potential pathway involved in concurrent inflammation and ankylosis in AS and IBD.

15.
Rheumatology (Oxford) ; 59(6): 1340-1346, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593590

RESUMO

OBJECTIVE: The aim of this study was to compare patients with ankylosing spondylitis with psoriasis (ASP) and without psoriasis (AS), to axial PsA (axPsA) patients. METHODS: Two adult cohorts were recruited from the AS clinic: ASP and AS. These two cohorts were compared with two adult cohorts recruited from the PsA clinic: axPsA (radiographic sacroiliitis: ⩾bilateral grade 2 or unilateral grade 3 or 4); and Peripheral PsA. All patients were followed prospectively according to the same protocol. The demographic, clinical and radiographic variables were compared. Adjusted means were used to account for varying intervals between visits. A logistic regression was performed and adjusted for follow-up duration. RESULTS: There were 477 axPsA patients, 826 peripheral PsA, 675 AS and 91 ASP patients included. AS patients were younger (P < 0.001), more male and HLA-B*27 positive (76%, 72% vs 64%, P ⩽ 0.001, 82%, 75%, vs 19%, P = 0.001). They had more back pain at presentation (90%, 92% vs 19%, P = 0.001), worse axial disease activity scores (bath ankylosing spondylitis disease activity index: 4.1, 3.9 vs 3.5 P = 0.017), worse back metrology (bath ankylosing spondylitis metrology index: 2.9, 2.2 vs 1.8, P < 0.001), worse physician global assessments (2.4, 2.2 vs 2.1, P < 0.001), were treated more with biologics (29%, 21% vs 7%, P = 0.001) and had a higher grade of sacroiliitis (90%, 84% vs 51%, P < 0.001). Similar differences were detected in the comparison of ASP to axPsA and in a regression model. CONCLUSION: AS patients, with or without psoriasis, seem to be different demographically, genetically, clinically and radiographically from axPsA patients. axPsA seems to be a distinct entity.


Assuntos
Artrite Psoriásica/diagnóstico por imagem , Psoríase/complicações , Espondilite Anquilosante/diagnóstico por imagem , Adulto , Artrite Psoriásica/complicações , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Espondilite Anquilosante/complicações , Adulto Jovem
16.
Arthritis Rheumatol ; 72(3): 428-434, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31599089

RESUMO

OBJECTIVE: Ankylosing spondylitis (AS) is an inflammatory arthritis in which men have a higher risk of developing progressive axial disease than women. Transcriptomic studies have shown reduced expression of cytotoxic cell genes in the blood of AS patients. HLA-B27 contributes the greatest risk for AS, suggesting a role for CD8+ T cells. This study was undertaken to profile AS patient cytotoxic cells with the hypothesis that an alteration in CD8+ T cells might explain the aberrant cytotoxic profile observed in patients. METHODS: Whole blood was examined for GZM and PRF1 gene expression by quantitative polymerase chain reaction. Serum and synovial fluid (SF) were examined for granzyme and perforin 1 expression by bead array, and blood and SF mononuclear cells were examined for granzyme and perforin 1 expression by fluorescence-activated cell sorting (FACS). RESULTS: GZM and PRF1 gene expression were both reduced in AS patients compared to healthy controls, especially in men. Perforin 1, but not granzyme, protein levels were reduced in AS patient serum. Granzymes were elevated in AS SF, but not in rheumatoid arthritis or osteoarthritis SF. FACS revealed a reduction in granzyme-positive and perforin 1-positive lymphocytes, but not an intrinsic defect in CD8+ T cell granzyme or perforin 1 production. CD8+ T cell frequency was reduced in the blood and increased in the SF of AS patients. CONCLUSION: Our findings indicate that AS patients have an altered cytotoxic T cell profile. These data suggest that CD8+ T cells with a cytotoxic phenotype are recruited to the joints, where they exhibit an activated phenotype. Thus, a central role for CD8+ T cells in AS may have been overlooked and deserves further study.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Citotoxicidade Imunológica/genética , Granzimas/imunologia , Perforina/imunologia , Espondilite Anquilosante/imunologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espondilite Anquilosante/genética
17.
J Rheumatol ; 47(4): 524-530, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31043543

RESUMO

OBJECTIVE: To compare clinical impression and confidence of extended role practitioners (ERP) with those of rheumatologists experienced in axial spondyloarthritis (axSpA) according to (1) evaluation of patients with chronic back pain assessed for axSpA; and (2) magnetic resonance imaging (MRI) recommendation for further investigation of these patients. METHODS: Patients with ≥ 3 months of back pain and age of onset < 45 years were referred for axSpA evaluation. An ERP assessed consecutive patients and recorded standardized clinical information in written form. Three rheumatologists subsequently evaluated each patient based on the recorded information. Patients were classified as having axSpA or mechanical back pain based on clinical and investigative findings. Level of confidence was noted for classification and MRI indication. Agreement between assessors was evaluated using percentage agreement and κ coefficient. RESULTS: Fifty-seven patients were assessed. Interobserver agreement of clinical impression for all raters was moderate (κ = 0.52). Agreement of clinical impression between ERP and rheumatologists ranged between 71.2% (κ = 0.41) and 79.7% (κ = 0.57). Agreement of clinical impression among rheumatologists ranged from 74.1% (κ = 0.49) to 79.7% (κ = 0.58). All rater agreement for MRI indication was fair (κ = 0.37). ERP agreement with rheumatologist for MRI recommendation ranged from 64.2% (κ = 0.32) to 75% (κ = 0.48). Agreement for MRI indication among rheumatologists ranged from 62.9% (κ = 0.27) to 74% (κ = 0.47). Confidence in clinical impression was similar among all practitioners. CONCLUSION: ERP with specialty training in inflammatory arthritis demonstrate clinical impressions comparable with those of rheumatologists in the assessment of axSpA. Incorporation of such roles into existing models of care may assist in early detection of axSpA.

18.
Front Immunol ; 11: 601886, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33488597

RESUMO

The severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2) that appeared in December 2019 has precipitated the global pandemic Coronavirus Disease 2019 (COVID-19). However, in many parts of Africa fewer than expected cases of COVID-19, with lower rates of mortality, have been reported. Individual human leukocyte antigen (HLA) alleles can affect both the susceptibility and the severity of viral infections. In the case of COVID-19 such an analysis may contribute to identifying individuals at higher risk of the disease and the epidemiological level to understanding the differences between countries in the epidemic patterns. It is also recognized that first antigen exposure influences the consequence of subsequent exposure. We thus propose a theory incorporating HLA antigens, the "original antigenic sin (OAS)" effect, and presentation of viral peptides which could explain with differential susceptibility or resistance to SARS-CoV-2 infections.


Assuntos
/imunologia , Antígenos HLA/imunologia , Imunidade/imunologia , /imunologia , Animais , Humanos , Pandemias/prevenção & controle
20.
Artigo em Inglês | MEDLINE | ID: mdl-31675169

RESUMO

OBJECTIVES: Using a longitudinal observational cohort of ankylosing spondylitis (AS) patients, we sought to identify progression rates, and factors predictive of spinal progression. As a secondary aim we analyzed the effect of tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression. METHODS: AS patients who had baseline and follow-up cervical and lumbar X-rays were included in the study. Radiographic damage was assessed by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A change of 2 mSASSS units in 2 years was defined as progression. The characteristics of the study group such as demographic, clinical, laboratory, and treatment history were collected. RESULTS: There were 350 patients in the study. The mean mSASSS increased from 9.3 (15.8) units at baseline to 17.7 (21.7) units by the 6th year. Change in mSASSS scores between the 0 to 2, 2 to 4 and 4 to 6 years were 1.23 (2.68), 1.47 (2.86), and 1.52 (3.7) units respectively. Overall 24.3% of the group progressed in 2 years' time. Male sex (HR 2.46, 95%CI 1.05, 5.76), presence of baseline damage (HR 7.98, 95%CI 3.98, 16), increased inflammatory markers (logCRP; HR 1.35, 95%CI 1.07, 1.70) and TNFi use (HR 0.82, 95%CI 0.70, 0.96) were predictive of radiographic progression. There was a 20% reduction in the rate of progression with TNFi. CONCLUSION: Male sex, presence of baseline damage, active disease state and higher inflammatory markers confer a high-risk group for disease progression. Treatment with TNFi showed a disease modifying effect by slowing the rate of radiographic progression.

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