Search

Disorders of the immune system, including immunodeficiency, immuno-malignancy, and (auto)inflammatory, autoimmune, and allergic diseases, have a great impact on a host's health. Cellular communication mediated through cell surface receptors, among different cell types and between cell and microenvironment, plays a critical role in immune responses. Selective members of the adhesion G protein-coupled receptor (aGPCR) family are expressed differentially in diverse immune cell types and have been implicated recently in unique immune dysfunctions and disorders in part due to their dual cell adhesion and signaling roles. Here, we discuss the molecular and functional characteristics of distinctive immune aGPCRs and their physiopathological roles in the immune system. [ABSTRACT FROM AUTHOR]

Higher soluble CD4 (sCD4) levels in serum have been detected in patients of infectious and chronic inflammatory diseases. However, how and why sCD4 is produced remains poorly understood. We establish sensitive ELISA and WB assays for sCD4 detection in conditioned medium of in vitro cell culture system and serum of chronic inflammatory patients. Serum samples from patients with systemic lupus erythematosus (SLE) (n = 79), rheumatoid arthritis (RA) (n = 59), ankylosing spondylitis (AS) (n = 25), gout (n = 31), and normal controls (n = 99) were analyzed using ELISA for sCD4 detection. Results from each assay were analyzed by the Kruskal-Wallis test. Dunn’s multiple comparison post-test was then applied between groups. We confirm that cells expressing exogenous CD4 produce sCD4 in a constitutive and PMA-induced manner. Importantly, sCD4 production in a heterologous expression system is inhibited by GM6001 and TAPI-0, suggesting receptor shedding by matrix metalloproteinase (MMP)-like proteinases. Moreover, similar findings are recapitulated in human primary CD4+ T cells. Finally, we show that serum sCD4 levels are increased in patients of chronic inflammatory diseases including RA and SLE, but not in those with gout. Intriguingly, sCD4 levels in RA patients are correlated positively with the disease activities and higher sCD4 levels seem to associate with poor prognosis. Taken together, we conclude that CD4 is shed from cell surface by a MMP-like sheddase and sCD4 level is closely related with the inflammatory condition in certain chronic diseases. Hence, sCD4 might be considered an important parameter for RA disease progression with potential diagnostic importance. [ABSTRACT FROM AUTHOR]

Focuses on the physicochemical properties of the spherical molecules which were a production of the incorporation of carbon molecules into the interlayer of a magnesium/aluminium double hydroxide compound. How the molecules were arranged; What precursor was used; How was the carbon molecules were introduced; Characterization of the compound by various methods including carbon nuclear magnetic resonance spectroscopy.

Objectives: To estimate stroke risk in Taiwanese patients with gout. Methods: We enrolled patients from the Taiwan National Health Insurance Database, with gout diagnosed from 2000 to 2008, and followed them up until December 2018. This cohort was propensity score-matched according to birth year, sex, the date of diagnosis of gout, comorbidities, and co-medications with individuals without gout (controls) (n = 310,820 in each group). Stroke was defined as the primary diagnosis at discharge after the index date. To evaluate ischemic and hemorrhagic stroke risks, we calculated their incidence, hazard ratio (HR), and two-year moving average incidence rate. Results: The incidence (95% CI) and HR of ischemic stroke were lower in the gout group than in the control group in the first 3 years (incidence: 4.74 [4.60–4.88] vs. 5.17 [5.03–5.32] per 1000 person-years; HR: 0.92 [0.88–0.96]), then became significantly higher than in the control group after 3 years (incidence: 4.10 [4.04–4.16] vs. 3.81 [3.75–3.87] per 1000 person-years; HR: 1.08 [1.05–1.10]). Similarly, the incidence (95% CI) and HR of hemorrhagic stroke was lower in the gout group than in the control group in the first 3 years (incidence: 1.51 [1.43–1.59] vs. 1.70 [1.62–1.79] per 1000 person-years; HR: 0.88 [0.82–0.92]), then became significantly higher than in controls after 3 years (incidence: 1.43 [1.39–1.46] vs. 1.26 [1.22–1.29] per 1000 person-years; HR: 1.14 [1.10–1.18]). Conclusions: In Taiwan, patients with gout had higher risks of ischemic and hemorrhagic stroke after 3 years. [ABSTRACT FROM AUTHOR]

GPR56 is a multi-functional adhesion-class G protein-coupled receptor involved in biological systems as diverse as brain development, male gonad development, myoblast fusion, hematopoietic stem cell maintenance, tumor growth and metastasis, and immune-regulation. Ectodomain shedding of human GPR56 receptor has been demonstrated previously, however the quantitative detection of GPR56 receptor shedding has not been investigated fully due to the lack of appropriate assays. Herein, an efficient system of expression and immune-affinity purification of the recombinant soluble extracellular domain of human GPR56 (sGPR56) protein from a stably transduced human melanoma cell line was established. The identity and functionality of the recombinant human sGPR56 protein were verified by Western blotting and mass spectrometry, and ligand-binding assays, respectively. Combined with the use of two recently generated anti-GPR56 monoclonal antibodies, a sensitive sandwich ELISA assay was successfully developed for the quantitative detection of human sGPR56 molecule. We found that GPR56 receptor shedding occurred constitutively and was further increased in activated human melanoma cells expressing endogenous GPR56. In conclusion, we report herein an efficient system for the production and purification of human sGPR56 protein for the establishment of a quantitative ELISA analysis of GPR56 receptor shedding. [ABSTRACT FROM AUTHOR]

The association between the gut microbiota and the development of lupus is unclear. We investigated alterations in the gut microbiota after induction of lupus in a murine model using viral peptide of human cytomegalovirus (HCMV). Three treatment arms for the animals were prepared: intraperitoneal injection of HCMVpp65 peptide, adjuvant alone, and PBS injection. Feces were collected before and after lupus induction biweekly for 16S rRNA sequencing. HCMVpp65 peptide immunization induced lupus-like effects, with higher levels of anti-dsDNA antibodies, creatinine, proteinuria, and glomerular damage, compared with mice treated with nothing or adjuvant only. The Simpson diversity value was higher in mice injected with HCMVpp65 peptide, but there was no difference in ACE or Chao1 among the three groups. Statistical analysis of metagenomic profiles showed a higher abundance of various families (Saccharimonadaceae, Marinifiaceae, and Desulfovibrionaceae) and genera (Candidatus Saccharimonas, Roseburia, Odoribacter, and Desulfovibrio) in HCMVpp65 peptide-treated mice. Significant correlations between increased abundances of related genera (Candidatus Saccharimonas, Roseburia, Odoribacter, and Desulfovibrio) and HCMVpp65 peptide immunization-induced lupus-like effects were observed. This study provides insight into the changes in the gut microbiota after lupus onset in a murine model. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) has been linked to the triggering of systemic lupus erythematosus (SLE). We proposed that B cell epitope region of HCMV phosphoprotein 65 (HCMVpp65)422–439 mimics an endogenous antigen and initiates lupus-like autoimmunity. Amino acid homology between HCMVpp65422-439 and TAF9134-144 (TATA-box binding protein associated factor 9, TAF9) was investigated using a similarity search in NCBI protein BLAST program (BLASTP). A murine model was used to confirm their antigenicity and ability to induce lupus-like symptoms. HCMVpp65422-439 induced immune responses with the presence of specific antibodies against HCMVpp65422-439 and TAF9134-144, as well as anti-nuclear and anti-double-stranded (ds)DNA antibodies that are characteristic of SLE. In addition, the majority of HCMVpp65422-439 and TAF9134-144 immunized mice developed proteinuria, and their renal pathology revealed glomerulonephritis with typical abnormalities, such as mesangial hypercellularity and immune complex deposition. Immunoglobulin eluted from the glomeruli of HCMVpp65422-439 immunized mice showed cross-reactivity with TAF9134-144 and dsDNA. Increased anti-TAF9 antibody activity was also observed in the sera from SLE patients compared with healthy people and disease controls. Molecular mimicry between HCMVpp65 peptide and host protein has the potential to drive lupus-like autoimmunity. This proof-of-concept study highlights the mechanisms underlying the link between HCMV infection and the induction of SLE. [ABSTRACT FROM AUTHOR]

• Les complications fœtales étaient plus fréquentes chez les nouveau-nés de mères atteintes de lupus érythémateux systémique ou de polyarthrite rhumatoïde. • Le risque de trouble du spectre autistique n'était pas élevé chez les enfants de mères atteintes de lupus érythémateux systémique ou de polyarthrite rhumatoïde. • Des facteurs de risque traditionnels, notamment âge maternel et score d'Apgar, ont été associés aux troubles du spectre autistique chez les nouveau-nés de mères atteintes de lupus érythémateux systémique ou de polyarthrite rhumatoïde. Déterminer si les nouveau-nés de mères taïwanaises atteintes de lupus érythémateux systémique ou de polyarthrite rhumatoïde ont plus de risques de présenter des troubles du spectre autistique. Nous avons identifié dans la base de données de l'assurance maladie nationale et le registre national des naissances une cohorte de toutes les naissances vivantes à Taïwan entre 2001 à 2012. Les enfants dont la mère était atteinte de lupus érythémateux systémique ou de polyarthrite rhumatoïde ont été identifiés et appariés à huit témoins selon l'âge maternel, le score d'Apgar à 1 minute, le score d'Apgar à 5 minutes, le type d'accouchement, le sexe de l'enfant, l'âge gestationnel, le poids de naissance et le lieu de résidence. Des modèles marginaux de régression de Cox ont été utilisés pour estimer le risque relatif (RR), avec un intervalle de confiance à 95 %, de TSA chez les nouveau-nés. Sur 1 893 244 nouveau-nés, 0,08 % (n = 1594) avaient une mère atteinte de lupus érythémateux systémique et 0,04 % (n = 673), une mère atteinte de polyarthrite rhumatoïde. Au total, 5 enfants de mère atteinte de polyarthrite rhumatoïde sur 673 (0,74 %), 7 enfants de mère atteinte de lupus érythémateux systémique sur 1594 (0,44 %) et 10 631 enfants de la cohorte totale de 1 893 244 (0,56 %) nouveau-nés présentaient des TSA. L'incidence des TSA (par 100 000 personnes-année) était de 140,39 (IC 95 % 45,58–327,62) dans le groupe polyarthrite rhumatoïde et de 76,19 (IC 95 % 30,63–156,97) dans le groupe lupus érythémateux systémique. Le risque de TSA n'était donc pas significativement plus élevé chez les nouveau-nés de mère atteinte de polyarthrite rhumatoïde (HR 1,42 ; IC 95 % 0,60–3,40) ou de lupus érythémateux systémique (HR 0,76 ; IC 95 % 0,36–1,59). Dans cette étude, les nouveau-nés dont la mère est atteinte de lupus érythémateux systémique ou de polyarthrite rhumatoïde n'ont pas plus de risques de présenter des troubles du spectre autistique. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether offspring of Taiwanese mothers with systemic lupus erythematosus or rheumatoid arthritis have a higher risk of autism spectrum disorder.Methods: Using the National Health Insurance database and National Birth Registry, we identified a cohort of all live births in Taiwan between 2001 and 2012. Children born to mothers with systemic lupus erythematosus or rheumatoid arthritis were identified and matched with up to 8 controls by maternal age, 1-minute Apgar score, 5-minute Apgar score, mode of delivery, sex of the child, gestational age, birth weight and place of residence. Marginal Cox proportional hazard models were used to estimate relative risk (RR) with 95% confidence intervals (CI) for ASD in offspring.Results: Of 1,893,244 newborns, 0.08% (n=1594) were born to systemic lupus erythematosus mothers, and 0.04% (n=673) were born to rheumatoid arthritis mothers. Overall, 5 of 673 (0.74%) offspring of rheumatoid arthritis mothers, 7 of 1594 (0.44%) offspring of systemic lupus erythematosus mothers and 10,631 of 1,893,244 (0.56%) offspring of all mothers developed autism spectrum disorder. Autism spectrum disorder incidence (per 100,000 person-years) was 140.39 (95% CI, 45.58-327.62) for the rheumatoid arthritis group and 76.19 (95% CI, 30.63-156.97) for the systemic lupus erythematosus group. Autism spectrum disorder risk was not significantly higher for children born to mothers with rheumatoid arthritis (HR, 1.42; 95% CI, 0.60-3.40) or systemic lupus erythematosus (HR, 0.76; 95% CI, 0.36-1.59).Conclusions: Children born to women with systemic lupus erythematosus or rheumatoid arthritis do not have a higher risk of autism spectrum disorder. [ABSTRACT FROM AUTHOR]

Abstract: Alzheimer's disease (AD) progresses insidiously from the preclinical stage to dementia. While people with subjective cognitive decline (SCD) have normal cognitive performance, some may be in the preclinical stage of AD. Neurofibrillary tangles appear first in the transentorhinal cortex, followed by the entorhinal cortex in the clinically silent stage of AD. We expected the earliest changes in subjects with SCD to occur in medial temporal subfields other than the hippocampal proper. These selective structural changes would affect specific memory subcomponents. We used the Family Picture subtest of the Wechsler Memory Scale‐III, which was modified to separately compute character, activity, and location subscores for episodic memory subcomponents. We recruited 43 subjects with SCD, 44 subjects with amnesic mild cognitive impairment, and 34 normal controls. MRI was used to assess cortical thickness, subcortical gray matter volume, and fractional anisotropy. The results demonstrated that SCD subjects showed significant cortical atrophy in their bilateral parahippocampus and perirhinal and the left entorhinal cortices but not in their hippocampal regions. SCD subjects also exhibited significantly decreased mean fractional anisotropy in their bilateral uncinate fasciculi. The diminution of cortical thickness over the mesial temporal subfields corresponded to brain areas with early tangle deposition, and early degradation of the uncinate fasciculus was in accordance with the retrogenesis hypothesis. The parahippocampus and perirhinal cortex contribute mainly to context association memory while the entorhinal cortex, along with the uncinate fasciculus, contributes to content‐related contextual memory. We proposed that context association and related memory structures are vulnerable in the SCD stage. [ABSTRACT FROM AUTHOR]

Cells respond to diverse types of mechanical stimuli using a wide range of plasma membrane-associated mechanosensitive receptors to convert extracellular mechanical cues into intracellular signaling. G protein-coupled receptors (GPCRs) represent the largest cell surface protein superfamily that function as versatile sensors for a broad spectrum of bio/chemical messages. In recent years, accumulating evidence has shown that GPCRs can also engage in mechano-transduction. According to the GRAFS classification system of GPCRs, adhesion GPCRs (aGPCRs) constitute the second largest GPCR subfamily with a unique modular protein architecture and post-translational modification that are well adapted for mechanosensory functions. Here, we present a critical review of current evidence on mechanosensitive aGPCRs. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Accumulating evidence suggests that gout is associated with increased overall and cardiovascular mortality. Using data from a large consecutive cohort of gout sufferers who were followed for 8 years, we investigated mortality among gout sufferers and compared the results with data from the general population of Taiwan. Methods: The study comprised 6631 people who had gout diagnosis at outpatient department of the Chang Gung Memorial Hospital in 2000. Survival status and cause of death were ascertained by examining the National Death Registry of Taiwan through 2008. Results: During 53,048 person-years of follow-up in 6631 gout patients, 1273 (male, 941; female, 332) deaths were identified, corresponding to the crude mortality rate was 21.3 (male, 20.0; female, 26.1) per 1000 patient-years, which was significantly higher than that of the national population. As compared with the national population of Taiwan in 2000, the all-cause standardized mortality ratio (95% confidence interval) was 1.29 (1.21–1.37) for men and 1.70 (1.53–1.89) for women. Both men and women in this cohort had higher standardized mortality ratios for death due to kidney diseases (men, 3.10; women, 3.54), endocrine and metabolic diseases (men, 2.24; women, 2.71), and cardiovascular diseases (men, 1.58; women, 1.81). Multivariate Cox regression showed no difference in mortality between genders. Discussion/Conclusions: Individuals with gout have increased mortality risk in both sexes; however, the extent of risk increment is higher in women. Kidney diseases, endocrine and metabolic diseases, and cardiovascular diseases are primary causes of death. [Copyright &y& Elsevier]

Résumé: Objectifs: De nombreuses données suggèrent que la goutte est associée à une augmentation de la mortalité globale et cardiovasculaire. Nous avons étudié la mortalité chez les patients goutteux au sein d’une importante cohorte de patients consécutifs atteints de goutte et suivis pendant huit ans, puis nous avons comparé les résultats avec les données de la population générale taïwanaise. Méthodes: Cette étude comportait 6631 patients qui avaient un diagnostic de goutte, issus des consultations du service de l’hôpital Chang Gung Memorial en 2000. La survie et la cause du décès ont été déterminées en examinant le registre national des décès de Taiwan jusqu’en 2008. Résultats: Pendant le suivi de 53 048 patients-années chez 6631 patients goutteux, 1273 (hommes, 941 ; femmes 332) décès ont été identifiés, ce qui correspond à un taux de mortalité brute de 21,3 (homme, 20,0 ; femme, 26,1) pour 1000 patients-années, taux significativement plus élevé que celui de la population nationale. En comparaison à la population nationale taïwanaise en 2000, le ratio de mortalité standardisés toutes causes (95 % de l’intervalle de confiance) était de 1,29 (1,21–1,37) pour les hommes et de 1,70 (1,53–1,89) pour les femmes. Dans cette cohorte, les hommes et les femmes avaient des ratios de mortalité standardisé plus élevés pour les décès liés aux maladies rénales (hommes, 3,10 ; femmes, 3,54), aux maladies métaboliques (hommes, 2,24 ; femmes, 2,71) et aux maladies cardiovasculaires (hommes, 1,58 ; femmes, 1,81). Une régression multivariée par modèle de Cox n’a pas mis en évidence de différence de mortalité entre les sexes. Discussion/Conclusions: Les patients taïwanais atteints de goutte ont un risque plus élevé de mortalité pour les deux sexes ; cependant, l’augmentation du risque est plus importante chez la femme. Les maladies rénales, endocriniennes et métaboliques ainsi que les maladies cardiovasculaires sont les principales causes de décès. [Copyright &y& Elsevier]