Significance Of Th22cells And Related Cytokine IL-22 On Patients With Rheumatoid Arthritis Complicated With Interstitial Lung Disease

Objective: Rheumatoid arthritis(RA) is a kind of chronic systemic autoimmune disease with the joints inflammation. Until now, the pathogenic mechanism of RA is still unclear. Data have suggested that autoimmune response and associated cytokines contribute to the pathogenesis in RA. CD4+ T cells(Th) are essential regulators of immune responses and inflammatory diseases. Interleukin 22(IL-22)-producing T helper cells(Th22) are a new subset of T helper cells. The primary cytokine of Th22 cells, IL-22, exerts potent proinflammatory and joint-destructive activities. Many cytokines regulate the differentiation of Th22 cells, IL-6 and TNF-α induces Th22 cell differentiation in vivo, antigen presenting cells such as plasmacytoid dendritic cells through direct contact or indirect effect( the secretion of IL-22 and TNF- α) to induce Th22 cell polarization. The induction effect of Th22 cells and related cytokines IL-22 is extremely important in RA. The aim of this study was to assess the role of Th22 cells and related cytokines in RA by investigating the percentage of Th22 cells in Peripheral blood and the levels of related cytokines IL-22 in serum.Methods: 40 cases of RA patients who come from the Third Hospital of Hebei Medical University were collected during November 2013 to September 2014, including 20 cases of patients with ILD. This study divide the RA patients into two groups, the patients complicated with ILD named as RA-ILD group, the patients uncomplicated with ILD named as RA-NILD group. RA patients were consistent with the American College of Rheumatology(ACR)/(European Union of resistance Rheumatism, EULAR)RA classification standard revised in 2010, ILD diagnosis consistent with the standard of the diagnosis of ILD that put forward by American Thoracic Society/ European Respiratory Society in 2011. All patients were at least three months without receiving immunosuppressive therapy, also did not take the immunomodulatory drugs. All patients had active disease, DAS28 score was >3.2.20 healthy people were selected as normal control, 8 subjects were male, 12 subjects were female, with a mean age of(59.95±6.73) years. All healthy control had no autoimmune disease, viral hepatitis, HIV infection, without immune suppressing drugs treatment history. All people had normal liver and renal function.Flow cytometric analysis(FCM) was employed for detecting the percentage of peripheral blood Th22 cells in RA patients and healthy control group, Avidin biotin peroxidase complex enzyme-linked immunosorbent assay(ABC-ELISA) was used to measure the serum levels of IL-22. Compare the level of IL-22 expression in RA patients and healthy group, to find the difference between the two groups. The correlation coefficients and significances were calculated between the percentage of Th22 cells and the laboratory parameters.Data were analyzed by statistical software SPSS17.0 for windows. The mean number ± standard deviation( x ±s) was used to express the measurement data. T test and Wilcoxcon test were adopted for comparison between groups. Pearson’s correlation test was performed for correlationship. P value<0.05 was considered significant.Results:1 The description of the basic data: The RA group comprised 40 patients, including 14 cases of male, 26 cases of female, the course of the disease was from 1.5 month to 40 years, with median duration of 30 months, the mean age was(59.05±10.55) yr; In the group of 20 patients with RA-NILD, the course of the disease was from 2 month to 9 years, with median duration of 12 months. The mean age was(58.10±9.42) yr, and 7 subjects were male, 13 subjects were female. In the group of 20 patients with RA-ILD, the course of the disease was from 1.5 month to 40 years, with median duration of 1087 months. The mean age was(60.00±11.74) yr, and 7 subjects were male, 13 subjects were female. In 20 normal controls, with a mean age of(59.95±6.73) yr, 8 subjects were male, 12 subjects were female. There were no differences between the patients and normal subjects in age, gender(P>0.05). In the group of 20 patients with RA-NILD, the average ESR、CRP、DAS28 and RF were(66.23±28.46)mm/h,(32.09±29.82)mg/L,(6.04±0.71),(647.05±769.87). In the group of 20 patients with RA-NILD, the average ESR、CRP、DAS28 and RF were(58.75±27.04)mm/h,(31.84±32.56)mg/L,(5.91±0.78),(434.05±485.22). In the group of 20 patients with RA-ILD, the average ESR, CRP and DAS28 were(73.70 ± 28.52)mm/h,(32.35 ± 27.66)mg/L,(6.17 ± 0.63),(758.87±944.06). There were no differences between the RA-ILD group and RA-NILD group in age, gender and disease activity(P>0.05).2 The percentage of peripheral blood Th22 cells in RA and normal group: The percentage of peripheral blood Th22 cells in RA patients was(0.15±0.07)%, which were significantly higher than normal group(0.09±0.05)%(P<0.01). The percentage of peripheral blood Th22 cells in RA-ILD was(0.18±0.05)%, which were significantly higher than RA-NILD(0.13±0.05)%(P<0.05).3 IL-22 levels in serum of RA patients and normal group: The serum levels of IL-22 in RA patients were(83.35±6.99)ng/L, which were significantly higher than normal group(60.64±4.77)ng/L(P<0.01). The serum levels of IL-22 in RA-ILD patients were(86.85±5.81)ng/L, which were significantly higher than RA-NILD group(79.85±6.38)ng/L(P<0.01).4 The correlation between the percentage of peripheral blood Th22 cells in RA and the laboratory parameters of disease activity: According to correlation analysis, The percentage of peripheral blood Th22 cells in RA had significant positive correlation with ESR、RF and DAS28(r=0.336,0.377,0.577,P<0.05); The percentage of peripheral blood Th22 cells in RA-NILD had significant positive correlation with ESR and DAS28(r=0.609, 0.634, P<0.05); Th22 has no significant correlation with CRP and RF(P>0.05). The percentage of peripheral blood Th22 cells in RA-ILD had significant positive correlation with RF and DAS28(r=0.451, 0.520, P<0.01); Th22 has no significant correlation with CRP and ESR(P>0.01).5 The correlation between serum levels of the IL-22 and activity index of RA(ESR, CRP, RF,DAS28): According to correlation analysis, the level of IL-22 in serum had significant positive correlation with ESR and DAS28(r=0.406, 0.576, P<0.05); IL-22 has no correlation with CRP and RF(P>0.05); the level of IL-22 in serum of RA-ILD group had significant positive correlation with RF and DAS28(r=0.487, 0.486, P<0.05); IL-22 has no correlation with CRP(P>0.05); the level of IL-22 in serum RA-NILD group had significant positive correlation with ESR and DAS28(r=0.473, 0.632, P<0.05); IL-22 has no correlation with CRP and RF(P>0.05).Conclusions:1 The percentage of peripheral blood Th22 cells in RA was significantly higher than normal controls, and it had positive correlation with laboratory parameters of disease activity, which could provide it may play a certain role in the occurrence and development of RA.2 The percentage of peripheral blood Th22 cells in RA-ILD group were significantly higher than the RA-NILD group, which could provide it may play a certain role in RA with interstitial lung disease.