High Interleukin 21 Levels in Patients with Systemic Lupus Erythematosus: Association with Clinical Variables and rs2221903 Polymorphism.

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.

Exploring the Role of PD-1 in the Autoimmune Response: Insights into Its Implication in Systemic Lupus Erythematosus.

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.

Analysis of electronic apex locators in human teeth diagnosed with apical periodontitis

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.

Combinaciones de autoanticuerpos y su asociación con variables clínicas en artritis reumatoidea / Combinations of autoantibodies and their association with clinical variables in rheumatoid arthritis / Combinações de autoanticorpos e sua associação com variáveis clínicas na artrite reumatóide

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.

Polimorfismo -1123G mayor que C en el gen PTPN22 y anticuerpos antipéptido citrulinado cíclico en la artritis reumatoide / PTPN22 -1123G is greater than C polymorphism and anti-cyclic citrullinated protein antibodies in rheumatoid arthritis

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)