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Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and diverse tissue and organ inflammatory affections. Interleukin 21 (IL-21) is implicated in B cell survival, proliferation, differentiation, class switching, and immunoglobulin production; therefore, it is considered a key cytokine in the pathogenesis of SLE. However, its association with disease activity and clinical phenotypes remains unclear. We aimed to evaluate the association of IL-21 levels with the disease activity and clinical phenotypes in patients with SLE. Also, we analyzed the IL21 polymorphisms associated with increased IL-21 levels. Methods: The IL-21 serum levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. The rs2221903 and rs2055979 polymorphisms were assessed in 300 healthy controls (HCs) and 300 patients with SLE by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The levels of IL-21 were monitored during follow-up visits in 59 patients with SLE. Results: The patients with SLE showed higher IL-21 levels compared to the HCs. The IL-21 levels did not correlate with Mex-SLEDAI and were not different in patients with inactive, mild-moderate, and severe disease. The IL-21 levels were increased in patients with hematological affection. The ROC curve analysis revealed that the IL-21 levels had good predictive power in discriminating among patients with SLE and HCs. In a follow-up analysis, the levels of IL-21 remained higher in the patients with SLE even when the patients were in remission. Also, the rs2221903 polymorphism was associated with increased IL-21 levels. Conclusions: This study highlights the importance of IL-21 as a key cytokine in SLE. IL-21 levels are higher in patients with SLE and remain increased regardless of disease activity. According to the ROC analysis, IL-21 is a potential biomarker of SLE. Further longitudinal studies are needed to explore the relationship between IL-21 and the clinical phenotypes of SLE.
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Despite advances in understanding systemic lupus erythematosus (SLE), many challenges remain in unraveling the precise mechanisms behind the disease's development and progression. Recent evidence has questioned the role of programmed cell death protein 1 (PD-1) in suppressing autoreactive CD4+ T cells during autoimmune responses. Research has investigated the potential impacts of PD-1 on various CD4+ T-cell subpopulations, including T follicular helper (Tfh) cells, circulating Tfh (cTfh) cells, and T peripheral helper (Tph) cells, all of which exhibit substantial PD-1 expression and are closely related to several autoimmune disorders, including SLE. This review highlights the complex role of PD-1 in autoimmunity and emphasizes the imperative for further research to elucidate its functions during autoreactive T-cell responses. Additionally, we address the potential of PD-1 and its ligands as possible therapeutic targets in SLE.
Subject(s)
Autoimmunity , Lupus Erythematosus, Systemic , Programmed Cell Death 1 Receptor , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/metabolism , Humans , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/immunology , Animals , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolismABSTRACT
Introduction: B cell activating factor (BAFF) has an important role in normal B cell development. The aberrant expression of BAFF is related with the autoimmune diseases development like Systemic Lupus Erythematosus (SLE) for promoting self-reactive B cells survival. BAFF functions are exerted through its receptors BAFF-R (BR3), transmembrane activator calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA) that are reported to have differential expression on B cells in SLE. Recently, atypical B cells that express CD11c have been associated with SLE because they are prone to develop into antibody-secreting cells, however the relationship with BAFF remains unclear. This study aims to analyze the BAFF system expression on CXCR5- CD11c+ atypical B cell subsets double negative 2 (DN2), activated naïve (aNAV), switched memory (SWM) and unswitched memory (USM) B cells. Methods: Forty-five SLE patients and 15 healthy subjects (HS) were included. Flow cytometry was used to evaluate the expression of the receptors in the B cell subpopulations. Enzyme-linked immunosorbent assay (ELISA) was performed to quantify the soluble levels of BAFF (sBAFF) and IL-21. Results: We found increased frequency of CXCR5- CD11c+ atypical B cell subpopulations DN2, aNAV, SWM and USM B cells in SLE patients compared to HS. SLE patients had increased expression of membrane BAFF (mBAFF) and BCMA receptor in classic B cell subsets (DN, NAV, SWM and USM). Also, the CXCR5+ CD11c- DN1, resting naïve (rNAV), SWM and USM B cell subsets showed higher mBAFF expression in SLE. CXCR5- CD11c+ atypical B cell subpopulations DN2, SWM and USM B cells showed strong correlations with the expression of BAFF receptors. The atypical B cells DN2 in SLE showed significant decreased expression of TACI, which correlated with higher IL-21 levels. Also, lower expression of TACI in atypical B cell DN2 was associated with high disease activity. Discussion: These results suggest a participation of the BAFF system in CXCR5- CD11c+ atypical B cell subsets in SLE patients. Decreased TACI expression on atypical B cells DN2 correlated with high disease activity in SLE patients supporting the immunoregulatory role of TACI in autoimmunity.
Subject(s)
Autoimmune Diseases , Lupus Erythematosus, Systemic , Humans , Memory B Cells , B-Cell Activating Factor , B-Cell Maturation Antigen , B-LymphocytesABSTRACT
INTRODUCTION: Cytokine levels are related to the aethiopathogenia of acute apical abscesses (AAA); however, the specific cytokine profiles in these cases are unclear. This study aimed to investigate the changes in systemic cytokine levels in patients with AAA and trismus onset, postantibiotic treatment, and postroot canal disinfection. METHODS: In total, 46 AAA patients with trismus and 32 control subjects were included. After seven days of antibiotic therapy, root canal disinfection was performed in the AAA patients. The serum levels of cytokines were evaluated at basal, seven, and 14 days after endodontic treatment. Quantification of cytokines from T helper (Th) 1, Th2, Th17, and regulatory T cells profiles was determined using the BioPlex MagPix system, and the obtained data were analyzed using SPSS statistical software (P < .05). RESULTS: AAA patients showed higher tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6, and IL-10 levels than control subjects, at basal measurement (P < .05); there were similar levels of interferon gamma, IL-1ß, IL-4, and IL-17 between groups (P > .05). IL-6 and IL-10 levels decreased after antibiotic treatment (P < .05), which was also associated with clinical improvement in patients with AAA and trismus. Patients with AAA had a positive correlation with higher serum levels of IL-6 and IL-10. In addition, TNF-α levels decreased only after antibiotic and endodontic treatment. CONCLUSIONS: In conclusion, patients with AAA had increased systemic serum levels of TNF-α, IL-6, and IL-10. Moreover, increased levels of IL-6 and IL-10 are associated with acute inflammatory symptoms. However, IL-6 and IL-10 levels decreased after antibiotic treatment, while TNF-α levels decreased after antibiotic and endodontic treatment.
Subject(s)
Cytokines , Periapical Abscess , Humans , Interleukin-10 , Interleukin-6 , Tumor Necrosis Factor-alpha , Abscess , TrismusABSTRACT
BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune exocrinopathy characterized by lymphocytic infiltration, glandular dysfunction and systemic manifestations. Lyp protein is a negative regulator of the T cell receptor encoded by the tyrosine phosphatase nonreceptor-type 22 (PTPN22) gene. Multiple single-nucleotide polymorphisms (SNPs) in the PTPN22 gene have been associated with susceptibility to autoimmune diseases. This study aimed to investigate the association of PTPN22 SNPs rs2488457 (-1123 G>C), rs33996649 (+788 G>A), rs2476601 (+1858 C>T) with pSS susceptibility in Mexican mestizo subjects. METHODS: One hundred fifty pSS patients and 180 healthy controls (HCs) were included. Genotypes of PTPN22 SNPs were identified by PCR-RFLP. PTPN22 expression was evaluated through RT-PCR analysis. Serum anti-SSA/Ro and anti-SSB/La levels were measured using an ELISA kit. RESULTS: Allele and genotype frequencies for all SNPs studied were similar in both groups (p > 0.05). pSS patients showed 17-fold higher expression of PTNP22 than HCs, and mRNA levels correlated with SSDAI score (r2 = 0.499, p = 0.008) and levels of anti-SSA/Ro and anti-SSB/La autoantibodies (r2 = 0.200, p = 0.03 and r2 = 0.175, p = 0.04, respectively). Positive anti-SSA/Ro pSS patients expressed higher PTPN22 mRNA levels (p = 0.008), with high focus scores by histopathology (p = 0.02). Moreover, PTPN22 expression had high diagnostic accuracy in pSS patients, with an AUC = 0.985. CONCLUSIONS: Our findings demonstrate that the PTPN22 SNPs rs2488457 (-1123 G>C), rs33996649 (+788 G>A) and rs2476601 (+1858 C>T) are not associated with the disease susceptibility in the western Mexican population. Additionally, PTPN22 expression may be helpful as a diagnostic biomarker in pSS.
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AIM: The aim of this case-control study was to evaluate the association between the TNFSF13B rs9514828 (-871 C > T) polymorphism and soluble BAFF (sBAFF) in apical periodontitis (AP) patients. METHODOLOGY: Two hundred and sixty one healthy subjects (HS) and 158 patients with AP classified as: 46 acute apical abscess (AAA), 81 primary AP (pAP) and 31 secondary AP (sAP) patients were included. Genomic DNA (gDNA) was extracted from peripheral blood cells according to the salting out method. The TNFSF13B rs9514828 (NC_000013.11:g.108269025C > T) were identified using polymerase chain reaction (PCR) followed by restriction fragment length polymorphisms (RFLP). Serum sBAFF levels were measured by ELISA test. The chi-squared or Fisher's exact test was performed. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the risk of AP associated with the rs9514828. The Mann-Whitney U test and Kruskal-Wallis analysis were used for non-normally distributed data. Differences were considered significant with a p-value <.05. RESULTS: No differences in the genotype/allele frequencies were shown between HS and patients with AAA. However, the TT genotype (OR = 2.68, 95% CI: 1.10-6.53; p = .025) and T allele (OR = 1.46, 95% CI: 1.00-2.12; p = .045) were associated with increased risk of pAP. In contrast, the minor allele T significantly decreased the risk of sAP (OR = 0.49, 95% CI: 0.024-0.99; p = .043). sBAFF serum levels were increased in AAA and pAP compared with HS (p < .01 and p = .021, respectively). The AAA patients had higher sBAFF serum levels than pAP (p = .034) and sAP (p < .01). CONCLUSIONS: These results suggest that the TNFSF13B rs9514828 (-871 C > T) polymorphism is associated with pAP susceptibility and that BAFF is a cytokine that might be involved in acute and chronic AP. The future exploration of the rs9514828 polymorphism in other AP cohorts is recommended.
Subject(s)
B-Cell Activating Factor , Periapical Periodontitis , Humans , B-Cell Activating Factor/genetics , Case-Control Studies , Polymorphism, Single Nucleotide , Gene Frequency , Genotype , Periapical Periodontitis/genetics , Polymorphism, Restriction Fragment Length , Interleukin-4/genetics , Genetic Predisposition to Disease , AllelesABSTRACT
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with very heterogeneous clinical behavior between affected individuals. Therefore, the search for biomarkers clinically useful for the diagnosis, prognosis, and monitoring of the disease is necessary. Here, we determined the association between PTPN22, IL10, OAS2, and CD70 mRNA expression with the clinical characteristics and with the serum levels of IL-10, IFN-γ, and IL-17 in SLE patients. Forty patients with SLE and 34 control subjects (CS) were included, mRNA expression was determined by real-time qPCR and cytokine levels were quantified by a multiplex bead-based immunoassay. Compared to CS, SLE patients showed increased IL10 mRNA and high IL-10 and IL-17 serum levels; in contrast, PTPN22 mRNA and IFN-γ were decreased. PTPN22 and IL10 gene expression was negatively correlated with Mex-SLEDAI score and were notably downregulated in SLE patients with lupus nephritis. Interestingly, SLE patients with renal damage were the ones with the lowest levels of PTPN22 and IL10 mRNA and the highest SLEDAI scores. No associations were observed for OAS2 and CD70 mRNA and IL-10, IL-17, and IFN-γ. In conclusion, we suggest that the assessment of IL10 and PTPN22 mRNA could be useful for monitoring disease activity in SLE patients showing renal involvement.
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Background: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, which affects exocrine glands. T cell activation is a trigger mechanism in the immune response. Hyperreactivity of T cells and antibody production are features in pSS. ICOS can be critical in the pathogenesis of pSS. Methods: A total of 134 pSS patients and 134 control subjects (CS) were included. Genotyping was performed by PCR-RFLP. ICOS mRNA expression was quantified by real-time PCR, and CD4+ ICOS+ T cells were determined by flow cytometry. Results: The ICOS IVS1 + 173 T>C polymorphisms were not associated with susceptibility to pSS (p = 0.393, CI = 0.503−1.311). However, the c.1624 C>T polymorphism was associated with a reduction in the risk of development of pSS (p = 0.015, CI = 0.294−0.884). An increase in ICOS mRNA expression in patients was observed (3.7-fold). Furthermore, pSS patients showed an increase in membranal-ICOS expression (mICOS). High expression of mICOS (MFI) was associated with lymphocytic infiltration. Conclusions: The IVS1 + 173 polymorphism is not a genetic marker for the development of pSS, while c.1624 T allele was associated with a low risk. However, elevated mICOS expression in pSS patients with high lymphocytic infiltration was found. ICOS may have an important role in the immunopathogenesis of pSS and should be analyzed in T cell subsets in pSS patients as a possible disease marker.
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BACKGROUND: The increased expression of B cell-activating factor (BAFF) has been linked to autoantibody production in autoimmune diseases (ADs). The aim of this study was to investigate the association among TNFSF13B gene (OMIM: 603969) single nucleotide polymorphisms (SNPs), TNFSF13B mRNA, and soluble BAFF (sBAFF) expression in patients with rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). The diagnostic value of sBAFF also was evaluated by the area under the curve (AUC) of receiver operating characteristic or receptor (ROC) curves. METHODS: Genotypes of the TNFSF13B rs9514827 (-2841 T > C), rs1041569 (-2701 A > T) and rs9514828 (-871 C > T) SNPs were determined by PCR-RFLP assay. TNFSF13B mRNA and sBAFF expression were performed by RT-qPCR and ELISA, respectively. The study included 320 RA patients, 101 pSS patients, and 309 healthy subjects (HS). RESULTS: The rs9514828 T allele and the TAT haplotype were associated with an increased risk to develop RA. In both ADs, the TNFSF13B mRNA levels were increased in comparison with HS. The rs9514828 (-871 C > T) polymorphism was associated with increased gene expression in RA patients. Also, sBAFF levels were higher in both ADs, however pSS patients showed the highest sBAFF levels. sBAFF showed higher diagnostic performance for pSS with an AUC of 0.968, with a similar accuracy of anti-SSA/Ro antibody diagnosis (AUC = 0.974). CONCLUSIONS: Our findings demonstrate that the TNFSF13B rs9514828 (-871 C > T) polymorphism is a risk factor for RA in the western Mexican population. sBAFF levels may be a potential diagnosis biomarker in pSS.
Subject(s)
Arthritis, Rheumatoid , Sjogren's Syndrome , Arthritis, Rheumatoid/genetics , B-Cell Activating Factor/genetics , Genotype , Humans , Polymorphism, Single Nucleotide , RNA, Messenger/genetics , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/geneticsABSTRACT
Background: The B-cell activating factor (BAFF) controls the maturation and survival of B cells. An imbalance in this cytokine has been associated with systemic autoimmunity in SLE and lupus nephritis (LN). However, few investigations have evaluated the tissular expression of BAFF in LN. This study aimed to associate BAFF system expression at the tissular level with the proliferative LN classes. Methods: The analysis included eighteen kidney tissues, with sixteen LN (class III = 5, class IV = 6, class III/IV+V = 4, and class V = 1), and two controls. The tissular expression was evaluated with an immunochemistry assay. A Cytation5 imaging reader and ImageJ software were used to analyze the quantitative expression. A p-value < 0.05 was considered significant. Results: The expressions of BAFF, A proliferation-inducing ligand (APRIL), and their receptors were observed in glomerular, tubular, and interstitial zones, with BAFF being the most strongly expressed in the overall analysis. BAFF-Receptor (BR3), transmembrane activator and CALM interactor (TACI), and B-Cell maturation antigen (BCMA) displayed higher expressions in LN class IV in all zones analyzed (p < 0.05). Additionally, a positive correlation was found between APRIL, TACI, and BCMA at the glomerular level; BCMA and APRIL in the interstitial zone; and BR3, TACI, and BCMA in the tubule (p < 0.05). Conclusions: The expression of BAFF and BAFF receptors is mainly associated with LN class IV, emphasizing the participation of these receptors as an essential pathogenic factor in kidney involvement in SLE patients.
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BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients present heterogenic clinical and serological characteristics. This heterogenicity could be due to the cytokine microenvironment. Cytokine levels have been analyzed and reported individually, showing controversial results; for that reason, we considered essential to evaluate a cluster of cytokines and relate them with antibody levels and clinical characteristics to find pSS subgroups. METHODS: Ninety-nine pSS patients, diagnosed by the 2016 ACR/EULAR classification criteria, and 76 control subjects (CS) were included. Cytokine quantification was performed by Multiplex assay. Principal component analysis (PCA) was realized, and the K-mean test was used to identify clusters/groups. Groups were analyzed by the Kruskal-Wallis test and the Bonferroni test. RESULTS: Higher IFN-γ, IL-17F, IL-21, IL-23, IL-4, and IL-31 levels were observed in pSS patients in comparison with control subjects. PCA analysis showed three groups. The severe group was characterized by higher cytokine concentrations as well as an increase in clinical parameters such as antibody levels, damage index score, and others. The moderate group presented intermediate severity; meanwhile, the mild group presented the lowest severity. CONCLUSION: Cluster analysis revealed three groups that were different in cytokine levels and clinical parameters in which the mild group was defined by lower severity, the moderate group with intermediate severity, and the severe group with higher severity. This analysis could help subclassify the primary Sjögren syndrome patients for a better understanding of the clinical phenotype that impacts the treatment approach.
Subject(s)
Cytokines/blood , Sjogren's Syndrome/etiology , Adult , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Principal Component Analysis , Severity of Illness Index , Sjogren's Syndrome/bloodABSTRACT
B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) play central roles in B cell development and maturation. Soluble forms of their receptors can be generated by proteolytic cleavage; however, their physiological and clinical roles are unknown. This study aimed to assess the relationships between the receptor soluble B cell maturation antigen (sBCMA) and clinical variables in systemic lupus erythematosus (SLE) patients. Serum cytokine concentrations were measured by ELISA for 129 SLE patients and 34 healthy controls (HCs), and the expression of the receptor BCMA was evaluated on B and plasma cells from 40 subjects. SLE patients showed aberrant expression of the receptor BCMA on B and plasma cells. Soluble levels of the receptor sBCMA and its ligands sAPRIL and sBAFF were increased in SLE patients compared with HCs. Additionally, sBCMA (rs = 0.6177) and sAPRIL (rs = 0.4952) correlated strongly with disease activity. Active SLE patients who achieved low disease activity showed decreased sBCMA (53.30 vs 35.30 ng/mL; p < 0.05) and sBAFF (4.48 vs 2.27 ng/mL; p < 0.05) serum levels after treatment, while sAPRIL expression remained unchanged. At a cutoff value of 22.40 ng/mL, sAPRIL showed high sensitivity (96.12%) and specificity (94.12%) for discrimination between HCs and SLE patients, while sBAFF showed lower sensitivity (82.2%) but higher specificity (94.1%) at a cutoff of 1.195 ng/mL. Relatively high levels of sAPRIL and sBCMA clustered active SLE patients. The receptor sBCMA could be a potential biomarker of disease activity in SLE.
Subject(s)
B-Cell Maturation Antigen/blood , Lupus Erythematosus, Systemic/diagnosis , Adolescent , Adult , Aged , B-Cell Activating Factor/blood , Biomarkers/blood , Case-Control Studies , DNA-Binding Proteins/blood , Female , Healthy Volunteers , Humans , Lupus Erythematosus, Systemic/blood , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Reference Values , Transcription Factors/blood , Young AdultABSTRACT
Electronic apex locators (EAL) have been used to establish the working length (WL) in root canal treatment. In teeth diagnosed with apical periodontitis, resorption of tooth apical structures can lead to difficulties to obtain an appropriate WL. The aim was to compare the capacity of three EAL's (Root ZX II, Raypex 6 and Endo-Eze Quill) to locate the tip of the K-file between 0 to -0.5 mm from the apical foramen (AF) on teeth diagnosed with asymptomatic apical periodontitis (AAP). Electronic working length was performed on 60 roots with AAP. A K-file #15 was inserted in the root canal until the apical foramen (AF) was located, and followed was re-adjusted to -0.5 mm through observation in EAL display. The K-file was fixed to the tooth with composite and teeth were extracted. The 4 apical millimeters were worn out until the K-file could be seen and were prepared and measured its distance to AF in a scanning electron microscope. Appropriate WL was when the tip of the K-file was located between 0 to -0.5 mm from AF. Results: Root ZX II showed significant difference (p<0.01) with the other two EALs. Root ZX II presented the better performance than Raypex 6 or Endo-Eze Quill in teeth with AAP.
Subject(s)
Periapical Periodontitis , Tooth Apex , Dental Pulp Cavity , Electronics , Humans , Odontometry , Root Canal Preparation , Root Canal TherapyABSTRACT
Abstract Electronic apex locators (EAL) have been used to establish the working length (WL) in root canal treatment. In teeth diagnosed with apical periodontitis, resorption of tooth apical structures can lead to difficulties to obtain an appropriate WL. The aim was to compare the capacity of three EAL's (Root ZX II, Raypex 6 and Endo-Eze Quill) to locate the tip of the K-file between 0 to -0.5 mm from the apical foramen (AF) on teeth diagnosed with asymptomatic apical periodontitis (AAP). Electronic working length was performed on 60 roots with AAP. A K-file #15 was inserted in the root canal until the apical foramen (AF) was located, and followed was re-adjusted to -0.5 mm through observation in EAL display. The K-file was fixed to the tooth with composite and teeth were extracted. The 4 apical millimeters were worn out until the K-file could be seen and were prepared and measured its distance to AF in a scanning electron microscope. Appropriate WL was when the tip of the K-file was located between 0 to -0.5 mm from AF. Results: Root ZX II showed significant difference (p<0.01) with the other two EALs. Root ZX II presented the better performance than Raypex 6 or Endo-Eze Quill in teeth with AAP.
Resumo Os localizadores eletrônicos apicais têm sido usados para estabelecer o comprimento de trabalho no tratamento do canal radicular. Nos dentes diagnosticados com periodontite apical, a reabsorção das estruturas apicais dos dentes pode levar a dificuldades na obtenção de uma odontometria apropriada. Este estudo comparou três localizadores apicais (Root ZX II, Raypex 6 e Endo-Eze Quill) para localizar a ponta do instrumento K-file entre 0 a -0,5 mm do forame apical em dentes com diagnóstico de periodontite apical assintomática. O comprimento de trabalho eletrônico foi realizado em 60 dentes com periodontite apical assintomática. Uma lima K-file de número 15 foi inserida no canal radicular até a localização do forame apical, e seguida foi reajustada para -0,5 mm por meio de observação no visor do localizador eletrônico apical. A lima K-file foi fixada ao dente usando compósito, e a seguir os dentes foram extraídos. Os 4 milímetros apicais foram desgastados até que a lima K-file pudesse ser visualizada para as medidas de distância no forame apical por meio de microscópio eletrônico de varredura. O comprimento de trabalho apropriado foi determinado quando a ponta do instrumento estivesse localizada entre 0 a -0,5 mm do forame apical. O Root ZX II apresentou o melhor desempenho (p<0,01) que o Raypex 6 ou Endo-Eze Quill em dentes humanos com periodontite apical assintomática.
Subject(s)
Humans , Periapical Periodontitis , Tooth Apex , Root Canal Therapy , Root Canal Preparation , Dental Pulp Cavity , Electronics , OdontometryABSTRACT
The predominance of the effector mechanisms by CD4 + T cells is a characteristic of inflammatory autoimmune diseases such as rheumatoid arthritis (RA). The CD40/CD40L costimulatory pathway contributes to these pathogenic mechanisms by promoting autoantibody production and inflammation. Aberrant expression of CD40 and CD40L in RA patients has been shown, the latter prevailing in females. However, contrasting results have emerged regarding the clinical associations of these findings. We determined the association of CD40 and CD40L expression with the clinical activity evaluated through DAS28 in RA patients. A total of 38 female RA patients and 10 age- and sex-matched control subjects were included. CD40 and CD40L mRNA expression was quantified by real-time qPCR, cell surface proteins were determined by flow cytometry, and protein soluble forms were determined by ELISA. The expansion of a CD4 + T cell subpopulation expressing CD40 was identified in the RA group. In addition, high frequencies of CD4 + CD40L + T cells expressing high levels of CD40L, increased levels of sCD40L and overexpression of CD40L mRNA were observed in these patients. Moreover, there was a gradual increase in CD40L when data were stratified according to DAS28, except for very active patients. No correlation was observed between the levels of mRNA, cell surface protein and soluble protein of CD40 and CD40L with the clinical features of RA patients. There is an altered expression of CD40L in female RA patients in association with clinical activity assessed by DAS28, these findings support the evidence that suggests CD40L as a marker of clinical activity.
Subject(s)
Arthritis, Rheumatoid/immunology , CD40 Antigens/genetics , CD40 Antigens/metabolism , CD40 Ligand/genetics , CD40 Ligand/metabolism , Adult , Arthritis, Rheumatoid/genetics , Biomarkers/metabolism , CD4-Positive T-Lymphocytes/immunology , Case-Control Studies , Female , Humans , Middle Aged , Severity of Illness Index , Up-RegulationABSTRACT
B-cell activating factor (BAFF) is a major cytokine that regulates B-cell survival, maturation and differentiation through its binding with its receptors: BAFF receptor (BAFF-R), transmembrane activator and cyclophilin ligand interactor (TACI) and B-cell maturation antigen (BCMA). These receptors have been demonstrated to be involved in tertiary lymphoid structure formation; however, their role in germinal centers (GCs) has remained elusive. The aim of the present study was to determine the expression profiles of BAFF and its receptors in secondary lymphoid tissues. Tonsils resected due to chronic tonsillitis were used as lymphoid tissues. To confirm the presence of GCs identified based on their typical structure, CD21 antibody staining was employed. The expression of BAFF, BAFF-R, TACI and BCMA was assessed by immunohistochemistry. BAFF was highly expressed in all regions of the follicle, but the highest BAFF expression was detected in the mantle zone (MZ). A high expression of BAFF-R was observed on lymphocytes in the MZ in comparison with the other regions (~80%; P<0.05), which was co-localizated with BAFF (r=0.646; P<0.001), in the MZ. TACI and BCMA exhibited similar expression among the different zones of the GCs, and co-localization with BAFF was observed inside the follicle, mainly in the dark zone. The present results indicate that BAFF is implicated in the maintenance of GCs. BAFF-R overexpression in the MZ, co-localizated with BAFF, suggests that these proteins constitute the principal pathway for the maintenance of the naïve B-cell population. Furthermore, TACI and BCMA have a role in the GC, where processes of B-cell selection, proliferation and differentiation into immunoglobulin-secreting plasma cells occur.
ABSTRACT
BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by destruction of exocrine glands as a result of T and B cells infiltrated in glandular tissue. CD28 and CTLA-4 play a crucial role in T cell activation and inhibition. The aim of this study was to associate CD28 and CTLA4 haplotypes with susceptibility to pSS in patients from western Mexico. METHODS: Polymerase chain reaction and restriction fragment length polymorphism were performed to identify CD28 and CTLA4 genotypes in 111 patients with pSS and 138 control subjects (CS). Haplotype analysis was carried out by SHEsis program. Soluble serum levels of CD28 (sCD28) and CTLA-4 (sCTLA-4) were quantified by ELISA kit. RESULTS: The CD28 GC haplotype was associated with low risk to pSS (2.5-folds, P < 0.001). CTLA4 CAG and CGA were identified as genetic risk factor (P < 0.001;OR = 3.82[CI95%:2.022-7.296] and P < 0.001; OR = 11.38[CI95%:3.282-37.69] respectively). No difference in sCD28 and sCTLA-4 were found between patients and CS. However, pSS patients carriers of CD28 IVS3 + 17TC genotype showed high sCD28 (P = 0.039 vs TT carriers in CS). In regard to sCTLA-4, patient who carry CTLA4-319C>T, +49 A>G, and +6230 G>A, or their haplotypes did not show any difference. CONCLUSION: Our findings suggest that CD28 GC, CTLA4 CAG, and CGA haplotypes are associated with susceptibility to pSS in patients from western Mexico. It seems that genetic control of CD28 and CTLA4 as well as local immune response in glandular tissue may regulate the impact of the gene expression in pSS. It is necessary to confirm this hypothesis in an integrative study.
Subject(s)
CD28 Antigens/genetics , CTLA-4 Antigen/genetics , Genetic Predisposition to Disease/genetics , Sjogren's Syndrome/genetics , Cohort Studies , Female , Genetic Predisposition to Disease/epidemiology , Haplotypes/genetics , Humans , Mexico/epidemiology , Middle Aged , Polymorphism, Single Nucleotide/genetics , Sjogren's Syndrome/epidemiologyABSTRACT
Se evaluó la relevancia clínica de analizar conjuntamente dos nuevos autoanticuerpos (anti-vimentina citrulinada mutada: anti-MCV y anti-peptidil arginina desaminasa 4: anti-PAD4) en conjunto con los utilizados clásicamente en el diagnóstico (factor reumatoideo: FR y anticuerpos contra péptidos citrulinados cíclicos de la anti-CCP) en la artritis reumatoidea (AR). Los autoanticuerpos se determinaron mediante ensayos inmunoenzimáticos en suero de 370 pacientes con AR y 200 controles. Se observó que los anticuerpos anti-MCV presentaron la mayor especificidad de todos los analizados (100%), mientras que los anticuerpos anti-PAD4 presentaron la menor sensibilidad (24%) y especificidad (95%). El 4% de los individuos seronegativos a FR y anti-CCP fue seropositivo a anti-MCV o PAD4. Los pacientes triples seropositivos (FR, anti-CCP y anti-MCV) presentaron mayor inflamación sistémica/articular y actividad clínica que los que expresaron otras combinaciones de autoanticuerpos (p<0,001). Por otra parte, los pacientes sólo positivos a FR cursaron con menor inflamación y actividad clínica (p<0,001). En conclusión, la inclusión de los anticuerpos anti-MCV al panel utilizado para el diagnóstico de la AR (FR y anti-CCP) podría mejorar el diagnóstico oportuno de los individuos, principalmente en aquellos pacientes seronegativos a FR y anti-CCP. Por otra parte, existen perfiles de autoanticuerpos asociados a la actividad clínica de los pacientes.
In this paper it was evaluated the clinical relevance of analyzing together two new autoantibodies (anti-mutated citrullinated vimentin: anti-MCV and anti-peptidyl arginine deiminase type 4: anti-PAD4) and those used classically in the diagnosis (rheumatoid factor: RF and antibodies against cyclic citrullinated peptide: anti-CCP) of rheumatoid arthritis (RA). The autoantibodies were examined by immunoenzymatic assays in sera of 370 patients with RA and 200 controls. It was observed that anti-MCV antibodies have the highest level of specificity of all the analyzed (100%), while the anti-PAD4 antibodies have the lowest sensitivity (24%) and specificity (95%). Four percent of the individuals that were seronegative for RF and anti-CCP were seropositive for anti-MCV or PAD4. Triple seropositive patients (RF, anti-CCP, and anti-MCV) have greater systemic/ joint inflammation and clinical activity than those with other combinations of autoantibodies (p<0.001). Patients who are only positive for FR had less inflammation and clinical activity (p<0.001). In conclusion, the inclusion of anti-MCV antibodies into the panel used for the diagnosis of RA (RF and anti-CCP) could improve the early diagnosis of individuals, mainly in patients that were seronegative for RF and anti-CCP. On the other hand, there are profiles of autoantibodies associated with the clinical activity of RA patients.
O objetivo deste estudo foi avaliar a relevância clínica de analisar dois novos autoanticorpos (anti-vimentina citrulinada mutada: anti-MCV e anti-peptidilarginina deiminase 4: anti-PAD4) e os convencionalmente utilizados no diagnóstico (fator reumatóide: FR e anticorpos contra peptídeos citrulinados cíclicos: anti-CCP) da artrite reumatóide (AR). Os autoanticorpos foram avaliados através de ensaios imunoenzimáticos em soro de 370 doentes com AR e 200 controles. Foi observado que os anticorpos anti-MCV apresentaram o maior grau de especificidade de todos os analisados (100%), enquanto que os anticorpos anti-PAD4 apresentaram a menor sensibilidade (24%) e especificidade (95%). Quatro por cento dos indivíduos soronegativos para FR e anti-CCP foram soropositivos para anti-MCV ou PAD4. Os doentes tríplice soropositivos (FR, anti-CCP e anti-MCV) apresentam maior inflamação sistêmica/articular e atividade clínica do que aqueles com outras combinações de autoanticorpos (p<0.001). Os doentes apenas positivos para FR apresentaram menor inflamação e atividade clínica (p<0.001). Em conclusão, a inclusão dos anticorpos anti-MCV para o painel utilizado para o diagnóstico de AR (FR e anti-CCP) poderia melhorar o diagnóstico oportuno dos indivíduos, principalmente daqueles que são soronegativos para FR e anti-CCP. Por outro lado, existem perfis de autoanticorpos associados à atividade clínica de doentes.
Subject(s)
Humans , Arthritis, Rheumatoid , Arthritis, Rheumatoid/complications , Autoantibodies , Autoimmune Diseases , Data Interpretation, StatisticalABSTRACT
BACKGROUND: This study aimed to describe the anatomy of maxillary canines from a Western Mexican sub-population using micro-computed tomography (micro-CT). MATERIAL AND METHODS: Maxillary canines (n=32) were scanned at 19.6µm voxel resolution. Number and location of canals, the distance between the cemento-enamel junction and apex, occurrence of accessory and lateral canals, presence of oval canals, number of foraminas as well as two- (area, perimeter, roundness, aspect ratio, major and minor diameters) and three-dimensional (volume, surface area, and SMI) analysis were performed. Data of two-dimensional analyses at 5 different apical levels was statistically compared using Kruskal-Wallis tests (α=0.05). RESULTS: Overall, 31 specimens had one root with a main canal (Vertucci type I). Mean distance from the apex to the cemento-enamel junction was 16.32±2.27. Apical foraminas were present in 14 specimens (43.75%). No statistical differences were found in the two-dimensional analyses between the foramen and the 1 and 2mm apical levels (P >0.05). CONCLUSIONS: Maxillary canines presenting one root canal were present in a high percentage of cases (96%). The prevalence of long oval canals was <12% at the apical third and at least 37% of the sample showed more than one point of exit in the last apical 3mm. Key words:Maxillary canine, micro-computed tomography, root canal anatomy.
ABSTRACT
Introducción y objetivos: El gen de la proteína tirosina fosfatasa no receptora de tipo 22 (PTPN22) codifica la proteína linfoide tirosina fosfatasa -Lyp-, un importante regulador negativo de la activación de células T, que se ha asociado a distintos trastornos autoinmunitarios. El polimorfismo -1123G>C en el gen PTPN22 parece afectar al control de la transcripción de este gen, pero hasta la fecha, la importancia biológica sobre su contribución al riesgo de desarrollar artritis reumatoide (AR) sigue siendo desconocida. En el presente estudio evaluamos la asociación del polimorfismo -1123G>C con anti-cyclic citrullinated protein antibodies (anti-CCP, «anticuerpos antipéptido citrulinado cíclico») y el riesgo de desarrollar AR en la población del occidente de México. Materiales y métodos: Se realizó un estudio transversal analítico, en el que participaron 300 pacientes con AR clasificados de acuerdo con los criterios del ACR-EULAR y 300 sujetos control (SC). El polimorfismo -1123 G>C se genotipificó mediante PCR-RFLP. Los niveles de anticuerpos anti-CCP fueron cuantificados mediante una prueba de ELISA. Resultados: Encontramos una mayor prevalencia de genotipos homocigotos CC en SC en comparación con los pacientes con AR (OR 0,41; intervalo de confianza del 95% 0,24-0,71; p=0,001), lo que demuestra un posible efecto protector contra la AR. En cuanto a los niveles de anti-CCP, los portadores del genotipo CC mostraron los niveles más bajos en el grupo de AR (p<0,05). Conclusión: El genotipo CC del polimorfismo -1123G>C en el gen PTPN22 es un factor protector para la AR en la población mestiza mexicana y se asocia con niveles bajos de anticuerpos anti-CCP (AU)
Background and objectives: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase -Lyp- and has been associated with different autoimmune disorders. The PTPN22 -1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 -1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico. Material and methods: A transversal analytic study, which enrolled 300 RA patients classified according to ACR-EULAR criteria and 300 control subjects (CS) was conducted. The -1123 G>C polymorphism was genotyped by PCR-RFLP. The anti-CCP antibodies levels were quantified by ELISA kit. Results: We found a higher prevalence of homozygous PTPN22 -1123CC genotype in CS than in RA patients (OR 0.41; 95% confidence interval 0.24-0.71; P=.001), suggesting a potential protective effect against RA. Concerning anti-CCP levels, the CC genotype carriers showed the lowest median levels in RA (P<.05).Conclusion: The PTPN22 -1123CC genotype is a protector factor to RA in a Mexican-mestizo population and is associated with low anti-CCP antibodies (AU)