Receptors expressions on peripheral lymphocytes and CD4+ CD183+ as a diagnostics biomarker for rheumatoid arthritis: A case-control study in Ghana.

BACKGROUND: T cell receptors play important roles in the development and progression of rheumatoid arthritis (RA). Their involvement has been reported in inflammatory autoimmune diseases. However, their role in predicting RA is still under exploration. This study evaluated the expression of CD183 (CXCR3) receptors on T-cells and other relevant biomarkers for detecting RA and determine their relationship with disease activity. METHODS: This unmatched case-control study included 48 newly diagnosed RA patients and 30 apparent healthy controls from the orthopedic units of Komfo Anokye Teaching Hospital (KATH), Kumasi and Korle-Bu Teaching Hospital (KBTH), Accra, Ghana. Sociodemographic data was obtained, and blood samples were also collected and processed for flow cytometric analysis. Statistical analyses were done using SPSS version 26.0 and R programming language. p < .05 was considered statistically significant. RESULTS: This study found a significant difference in age group (p < .0001), marital status (p = .0210), occupation (p = .0140), educational level (p = .0210) and religion (p = .0100) between RA patients and healthy controls. Moreover, hemoglobin level (p = .0010), waist circumference (p < .0001) and hip circumference (p = .0040) were significantly different between RA patients and controls. RA patients had significantly lower levels of CD4+ CD183+ compared with the control group (p < .001), and was positively correlated with DAS score (r = .0397, p = .789). In Receiver Operator Characteristics analysis, CD4+ CD183+ could significantly detect RA with a high area under the curve (AUC = 0.687, p = .018). At a cut-off of 0.082, CD4+ CD183+ was the best receptor biomarker for detecting RA with a sensitivity of 90.0%, specificity of 25.9%, a positive predictive value of 69.2%, and a negative predictive value of 58.3%. CONCLUSION: CD4+ CD183+ best predict RA and is positively correlated with disease activity. CD4+ CD183+ could serve as diagnostics and disease-monitoring biomarker for RA; however, it demonstrates low specificity. Future studies should be directed on CD4+ CD183+ and other biomarkers to augment their diagnostics performances and routine management in RA.

CD8 Treg-Mediated Suppression of Naive CD4+ T Cell Differentiation into Follicular Helper T Cells.

BACKGROUND: The regulatory CD8+ T (CD8+ Treg) cells play an important role in immune tolerance and have been implicated in several human autoimmune diseases. In this context, follicular helper T (TFH) cells contribute by controlling the antibody production. In mice, CD8+ Treg cells control the number and function of TFH cells however the role of human CD8+ Treg cells on the differentiation of naive CD4+ T cells into TFH cells has not been studied. OBJECTIVES: Here, we evaluated the ability of human CD183+ CD8+ Treg cells to suppress TFH cell differentiation in vitro. METHODS: Activated CD183+CCR7+CD45RA-CD8+ Treg and CD183+CD25highICOS+CD8+ Treg cells were sorted and cocultured with naïve CD4+ T cells under TFH differentiation condition. The differentiation of TFH cells was evaluated by flow cytometry. RESULTS: Our results showed that activated CD183+CD8+ Treg cells upregulated the expression of Forkhead box P3 transcription factor, inducible T-cell co-stimulator (ICOS), and CD25 compared to CD183-CD8+ T cells. The CD183+CD25highICOS+CD8+ Treg cells suppressed TFH cell differentiation and CD4+ T cell proliferation in vitro which was not observed when CD183+CCR7+CD45RA-CD8+ Treg were cocultured with naïve CD4+ T cells under TFH cell differentiation condition. CONCLUSION: These results suggest that CD25highICOS+CD183+CD8+ Treg cells may regulate autoimmune and inflammatory responses mediated by TFH cells.

O receptor de quimiocina CXCR3/CD183 na tuberculose / The chemokine receptor CXCR3/CD183 in tuberculosis

Introdução: o receptor CXCR3/CD183 juntamente com seu indutor IFNy e seus ligantes CXCL9, CXCL10 e CXCL11 têm sido descritos como de grande importância na resposta imune do perfil T helper 1 (Th1). Este grupo de quimiocinas é expresso no microambiente e permite a migração de células ao sítio da infecção para combater o patógeno. Objetivo: revisar o atual estado da arte sobre o papel do receptor CXCR3/CD183 na tuberculose. Metodologia: o presente estudo inclui a revisão narrativa de 12 artigos que foram selecionados a partir de 74 artigos encontrados nas bases de dados PubMed e Sciencedirect entre primeiro de agosto e 31 de outubro de 2014. Resultados: diferentes abordagens vêm sendo utilizadas para o estudo desse receptor. A utilização de modelos animais como camundongos, coelhos e macacos é a mais comum. Porém, ensaios in vitro com células humanas do sangue periférico e efusão pleural também já foram utilizados para representar, com maior fidelidade, a resposta ao Mycobacterium tuberculosis (Mtb) pelo sistema imune humano. Esses estudos resultaram em importantes achados sobre o papel do receptor CXCR3 na tuberculose (TB), principalmente quanto à expressão em linfócitos e neutrófilos, assim como o padrão de coexpressão de outros receptores. Conclusão: o CXCR3 é o receptor de uma importante citocina (IP-10) induzida pelo IFN-gama, produzida na resposta Th1, eficaz na resposta à tuberculose. Nesse trabalho, resssalta-se que foram encontrados poucos estudos sobre o tema e isso demonstra a necessidade de realização de novas pesquisas, a fim de melhor investigar o papel desse importante receptor na tuberculose.

Introduction: the CXCR3/CD183 receptor along with its IFNy inducer and its ligands: the chemokines named CXCL9, CXCL10 and CXCL11 are of great importance in the Th1 (T helper 1) immune response. This group of chemokine modulates the migration of cells to the site of infection to defend against the pathogen. Objective: to investigate the current state of the art on the role of the receptor CXCR3/CD183 in tuberculosis. Methodology: the present study includes the narrative review of 12 articles that were selected from 74 articles found in the PubMed and Sciencedirect databases between August 1 and October 31, 2014. Results: different approaches have been used for the study of this receptor. The use of animal models such as mice, rabbits and monkeys is more common. However, in vitro assays with human peripheral blood cells and pleural effusion were also used to represent more faithfully the response to Mycobacterium tuberculosis (Mtb) by the human immune system. These studies resulted in significant findings on the role of the CXCR3 receptor in tuberculosis (TB), especially for expression in lymphocytes and neutrophils, as well as the pattern of co-expression of other receptors. Conclusion: CXCR3 is the receptor for an important cytokine (IP-10) induced by IFN-gamma, produced in the Th1 response, effective in responding to tuberculosis. In this work, it is emphasized that cheeses found few studies on the subject and demonstration, the need for conducting research, in order to better investigate the role of this important receptor in tuberculosis.