Serum interleukin-2 receptor α as a clinical biomarker in patients with systemic lupus erythematosus / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical relevance of serum interleukin-2 receptor α (IL-2Rα) in patients with systemic lupus erythematosus (SLE).@*METHODS@#One hundred and seven SLE patients and 39 healthy controls with comparable age and gender were recruited at Peking University People's Hospital from January 2019 to December 2020. Complete clinical data in 107 SLE patients at baseline and follow-up were collected. SLE disease activity index 2000 (SLEDAI-2K) was used to assess the disease activity of the SLE patients. The serum level of IL-2Rα in the SLE patients and healthy controls was measured using enzyme-linked immunosorbent assay (ELISA). The association between serum IL-2Rα and clinical and laboratory parameters was investigated. Mann-Whitney U test or t test, Chi-square test and Spearman correlation were used for statistical analysis.@*RESULTS@#The serum IL-2Rα levels were significantly higher in the SLE patients [830.82 (104.2-8 940.48) ng/L], compared with those in the healthy controls [505.1 (78.65-1 711.52) ng/L] (P < 0.001). Association analysis showed that the increased serum IL-2Rα was positively associated with SLEDAI-2K scores and anti-nucleosome antibody (r=0.357, P < 0.001; r=0.25, P=0.027, respectively). Thirty-six of 107 (33.6%) SLE patients had lupus nephritis. Serum IL-2Rα levels were significantly higher in the patients accompanied with lupus nephritis [1 102.14 (126.52-8 940.48) ng/L] than in the patients without lupus nephritis [743.89 (104.19-4 872.06) ng/L] (P=0.032). The patients in the high IL-2Rα group had more lupus nephritis compared with those in the low IL-2Rα group (40.8% vs. 19.4%, P=0.031). Meanwhile, SLEDAI-2K scores were found significantly higher in the high IL-2Rα group than in the low IL-2Rα group [10 (3-21) vs. 7 (3-16), P=0.001]. With the improvement of disease activity in the SLE patients after conventional treatments, serum levels of IL-2Rα [1 119.1 (372.25-2 608.86) ng/L] in the week 12 decreased significantly compared with the baseline [1 556.73 (373.08-8 940.48) ng/L] (P=0.042).@*CONCLUSION@#Serum IL-2Rα may be used as a biomarker of disease activity in patients with SLE. There is certain correlation between serum IL-2Rα and renal involvement in SLE.

Unbalanced expression of aryl hydrocarbon receptor in peripheral blood CCR6+CD4+ and CD4+CD25+T cells of rheumatoid arthritis / Expressão não equilibrada do receptor de hidrocarboneto arílico nos linfócitos T CCR6+ CD4+ e CD4+ CD25+ do sangue periférico na artrite reumatoide

ABSTRACT Objective: The goal of this study was to analyze the role of aryl hydrocarbon receptor in peripheral blood CCR6+CD4+ and CD4+CD25+T cells of patients with rheumatoid arthritis. Methods: Flow cytometry was applied to determine the proportion of AhR positive cells in CCR6+CD4+T, CD4+CD25+T and peripheral blood peripheral mononuclear cells from each subject. AhR mRNA and CYP1A1 mRNA relative expression levels were tested by real-time PCR. Results: The percentage of AhR positive cells in peripheral blood mononuclear cells was higher in RA group than that in healthy cases [(35.23 ± 10.71)% vs. (18.83 ± 7.32)%, p < 0.01]. The expression levels of AhR and CYP1A1 were both increased in patients with RA while compared to controls [(3.71 ± 1.63) vs. (2.00 ± 1.27), p = 0.002; (2.62 ± 2.08) vs. (0.62 ± 0.29), p < 0.01, respectively]. In RA patients, the percentage of AhR positive cells in CD4+CD25+T cells was significantly lower than that from controls [17.90 (6.10 ± 80.10)% vs. (52.49 ± 19.18)%, p < 0.01]; In healthy controls, the percentage of AhR positive cells in CD4+CD25+T cells was significantly higher than that in CCR6+CD4+T cells, and was also significantly higher than that in PBMCs [(52.49 ± 19.18)% vs. (23.18 ± 5.62)% vs. (18.06 ± 7.80)%, X 2 = 24.03, p < 0.01]; in RA patients, the percentage of AhR positive cells in CCR6+CD4+T cells was significantly increased than that in CD4+CD25+T cells and PBMCs [(46.02 ± 14.68)% vs. 17.90 (6.10 ± 80.10)% vs. (34.22 ± 10.33)%, X 2 = 38.29, p < 0.01]; Nevertheless, no statistically significant relationship was found between clinical data and AhR positive cells in CCR6+CD4+T and CD4+CD25+T cells. Conclusion: AhR may participate in the pathological progress of RA by controlling the differentiation of Th17 and Treg cells in peripheral blood.

RESUMO Objetivo: Analisar o papel do receptor de hidrocarboneto arílico (AhR) nos linfócitos T CCR6+ CD4+ e CD4+ CD25+ no sangue periférico de pacientes com artrite reumatoide (AR). Métodos: Foi aplicada citometria de fluxo para determinar a proporção de células AhR positivas em linfócitos CCR6+ CD4+ e CD4+ CD25+ do sangue periférico e células mononucleares periféricas de cada indivíduo. Os níveis de expressão relativa de ácido ribonucleico mensageiro (do inglês ribonucleic acid, RNAm,) de AhR e RNAm de enzima de primeiro estágio essencial para o AhR (CYP1A1) foram testados por reação em cadeia de polimerase (do inglês polymerase chain reaction, PCR,) em tempo real. Resultados: A percentagem de células AhR positivas nas células mononucleares do sangue periférico foi maior no grupo com AR do que nos indivíduos saudáveis [(35,23 ± 10,71)% vs. (18,83 ± 7,32)%, (p < 0,01)]. Os níveis de expressão de AhR e CYP1A1 estavam aumentados em pacientes com AR quando comparados com os controles [(3,71 ± 1,63) vs. (2,00 ± 1,27), p = 0,002; (2,62 ± 2,08) vs. (0,62 ± 0,29), p < 0,01, respectivamente]. Em pacientes com AR, a percentagem de células AhR positivas nos linfócitos T CD4+ CD25+ foi significativamente inferior à dos controles [17,90 (6,10 ± 80,10)]% vs. (52,49 ± 19,18)%, p < 0,01]; em controles saudáveis, a percentagem de células AhR positivas nos linfócitos T CD4+ CD25+ foi significativamente mais elevada do que nos linfócitos T CCR6+ CD4+ e também foi significativamente maior do que nas células mononucleares do sangue periférico (do inglês peripheral blood mononuclear cells, PBMC,) [(52,49 ± 19,18)% vs. (23,18 ± 5,62)% vs. (18,06 ± 7,80)%, X 2 = 24,03, p < 0,01]; em pacientes com AR, a percentagem de células AHR positivas nos linfócitos T CCR6+ CD4+ era significativamente maior em comparação com os linfócitos T CD4+ CD25+ e PBMC (46,02 ± 14,68)% vs. [17,90 (6,10 ± 80.10)]% vs. (34,22 ± 10,33)%, X2 = 38,29, p < 0,01]; no entanto, não foi encontrada correlação estatisticamente significativa entre os dados clínicos e células AhR positivas em linfócitos T CCR6+ CD4+ e CD4+ CD25+. Conclusão: O Ahr pode participar do progresso patológico da AR ao controlar a diferenciação de linfócitos Th17 e Treg no sangue periférico.

Immune-regulation in chronic hepatitis B virus infected patients

To assess the percentage of regulatory T cells in peripheral blood of chronic hepatits B [CHB] virus infected patients in comparison with that in healthy controls and to evaluate their suppressive activity on gamma-IFN production by T cells. The percentages of CD4+CD25+ and CD4+CD25+Foxp3+ regulatory T [Treg] cells were quantified in the peripheral blood of 59 chronic hepatitis B patients in comparison with that of 32 controls. And to assess Treg suppressive activity, the percentage of CD4+CD25+Foxp3+Tregs secreting interleukin-10 [IL-10] were evaluated together with the percentage of gamma interferon [gamma-IFN] secreting T cells. This study showed that the percentage of CD4+CD25+Tcells was significantly higher in CHB patients in comparison with healthy controls [mean, 11 +/- 1.7 vs. 36 +/- 4.0 P= 0.007]. A weak positive correlation was observed only between the percentage of CD4+CD25+Foxp3+T cells and serum alanine aminotransferase [ALT] levels [r=0.3, P=0.02]. These findings suggest that Tregs are capable of inhibiting the HBV immune response, which could contribute to persistence of HBV infection. Manipulating these regulatory cells represent an important objective in order to develop new anti-microbial immunotherapies, particularly for chronic infections

Clinical Relevance of Elevated Levels of Serum Soluble Interleukin-2 Receptor alpha (sIL-2Ralpha) in Patients with Non-Hodgkin's Lymphoma / 대한진단검사의학회지

Levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) are known to increase in the sera of patients with certain malignancies, including malignant lymphoma. This study aimed to assess the clinical significance of the sIL-2Ralpha level in non-Hodgkin's lymphoma (NHL). We used ELISA to measure the sIL-2Ralpha levels in 48 newly diagnosed and untreated patients with NHL and evaluated the correlation between the sIL-2Ralpha levels and clinical characteristics and the International Prognostic Index (IPI). We monitored serum sIL-2Ralpha in 7 patients to compare the changes in their clinical progress with these levels. High levels of serum sIL-2Ralpha (> or =2,000 U/mL) correlated well with parameters defining the high risk group according to the IPI, i.e., high tumor burden at diagnosis (stage III+IV) and lactate dehydrogenase > or =472 U/L. The levels were also associated with B symptoms, bone marrow involvement, and poor response to therapy. The sIL-2Ralpha level decreased during complete remission and was elevated during disease progression or relapse. A high level of sIL-2Ralpha was significantly associated with a low survival rate. These results suggest that serum sIL-2Ralpha might be useful as a biomarker for evaluating the prognosis of patients with NHL at the time of diagnosis and during therapy. A well-controlled, large-scale study is needed to clarify the clinical significance of sIL-2Ralpha in specific groups of NHL.