BackgroundIncreasing evidence indicates that cetuximab (CET) combined with chemoradiotherapy may be effective for patients with esophageal cancer. However, the recent results are still contradictory and no consensus has yet been reached on this issue. To evaluate the clinical effects and safety of CET, we conducted an updated meta-analysis by retrieving published data up to June 2018.MethodsA comprehensive literature search was performed in several electronic databases, including PubMed, Embase, the Cochrane Library, CNKI database and Chinese Biomedicine Database using subject terms and free terms. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine the efficiency and safety of CET.ResultsThis meta-analysis included 10 randomized controlled trials (RCTs). Five RCTs reported localized esophageal cancer and other five RCTs reported metastatic esophageal cancer. For these patients with localized esophageal cancer, CET could not significantly improve the response rate, overall survival and progression-free survival (PFS, 1–5 years). But CET treatment might increase the incidences of diarrhea (OR = 2.07; CI = 1.01–4.25) and rash (OR = 16.91; CI = 3.20–89.42). For other patients with metastatic esophageal cancer, the addition of CET significantly increased the response rate (OR = 3.34; CI = 1.90–5.88), disease control rate (OR = 2.92; CI = 1.49–5.71) and 2-year overall survival (OR = 2.78; CI = 1.20–6.46) compared with the control group. However, CET could not improve the 1-year overall survival and might make patients with metastatic esophageal cancer more susceptible to rash (OR = 5.50; CI = 2.14–14.14). No significant differences in other adverse effects were found between the two groups.ConclusionsOur findings suggested that adding CET to multimodal therapy significantly improved response rate and disease control rate for patients with metastatic esophageal cancer rather than patients with localized esophageal cancer. CET might be a safe therapeutic choice, but CET failed to significantly improve the overall survival and PFS for patients with localized or metastatic esophageal cancer.

Objective Accumulating evidence indicates that regulatory T cells (Tregs) may be involved in the pathogenesis of ankylosing spondylitis (AS). As different markers have been used to identify Tregs, some studies on the proportions of Tregs in AS patients have generated considerable controversy. To clarify the status of Tregs in such patients, we determine the proportion changes of peripheral Tregs during development of the disease, with different cellular markers. Methods We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov, and Clinical Trials.gov for the studies reporting the proportion of Tregs in AS patients. Using the PRISMA guidelines, we performed a random-effects meta-analysis of the frequencies of peripheral Tregs defined in different ways. Inconsistency was evaluated using the I-squared index (I2), and publication bias was assessed by examining funnel plot asymmetry using the Begger and Egger tests. Results A total 29 studies involving 1732 participants were included in the meta-analysis. Their conclusions of using the diversity of Tregs surface markers were inconsistent with each other. No significant difference in the proportions of Tregs was evident regardless of the definitions used [−0.709, (−1.455, 0.037, p = 0.063), I2 = 97.3%]. Six studies used “single CD25-positive” cells as Tregs, which revealed a significant increase in AS patients compared with healthy blood donors [0.736, (0.138, 1.334), p = 0.016, I2 = 80.7%]. Notably, the proportions of “CD4+CD25+FOXP3+,” “CD4+CD25highCD127low/−,” or “CD4+CD25+CD127low” T cells were lower in AS patients [−2.856, (−4.645, −1.066), p = 0.002; −1.812, (−2.648, −0.977), p < 0.001; −1.12, (−1.605, −0.635), p < 0.001]. Tregs defined as “CD25high,” “CD25bright,” “CD25bright/highCD127low/−,” “CD4+FOXP3+,” “CD4+CD25highFOXP3+,” and “CD4+CD25+CD127−” did not differ in proportion between AS patients and healthy blood donors. Conclusions The levels of Tregs varied based on the cellular identification markers used. The proportions of CD4+CD25+FOXP3+Tregs, CD4+CD25highCD127low/−, or CD4+CD25+CD127low in blood of AS patients were significantly decreased as compared with those in healthy blood donors, and our findings lend support to the idea that the Treg status of AS patients is important. And we recommend the above as the best definition of Tregs when evaluating the status of such patients.

Objective The absolute and relative changes of peripheral NK and T subsets are unclear in rheumatoid arthritis (RA) associated with pulmonary interstitial fibrosis (RA-ILD). To investigate the clinical risk factors, especially the changes of lymphocyte subsets, in RA-ILD in order to make early diagnosis and achieve prevention of the pulmonary interstitial lesions. Methods A total of 100 RA and 100 RA-ILD patients were enrolled. Rheumatoid factor, anti-cyclic citrulline peptide antibody, erythrocyte sedimentation rate, immunoglobulin, and C-reactive protein were examined. The percentage and absolute number of NK, T, B, Treg, Th1, Th2, and Th17 cells in peripheral blood were determined by flow cytometry. Results RA-ILD is more common in older and male RA patients and/or those with higher autoantibody titers. Flow cytometry showed that the absolute and relative numbers of CD56+ NK cells were significantly higher in RA-ILD (280.40 ± 180.51 cells/μl vs. 207.66 ± 148.57 cells/μl; 16.62 ± 8.56% vs. 12.11 ± 6.47%), whereas the proportion of T cells and CD4+ T cells was lower in peripheral blood of RA-ILD patients (69.82 ± 9.30%; 39.44 ± 9.87 cells/μl) than that in RA patients (74.45 ± 8.72%; 43.29 ± 9.10 cells/μl). Conclusions The occurrence of RA-ILD is closely related to the older male patients with high titer of various self-antibodies. Imbalance of CD3−CD56+ NK cells and T cells with other subsets were found in RA-ILD patients, which, together with older age, male, and high levels of autoantibodies should be considered as risk factors of pulmonary interstitial lesions.

BackgroundT lymphocytes are important contributors to systematic lupus erythematosus (SLE). Regulatory T (Treg) cells, with the capacity to suppress immune responses, effector T cells (Teff), which promote inflammation, have been intensively studied in recent years. However, previous reports describing the respective changes of Treg and Teff, especially T helper cells (Th17) in SLE patients were controversial. Here, we investigated both absolute number and percentage of CD4+CD25+Foxp3+Treg (CD4Treg) cells and effector cells on a large scale and the role of low-dose interleukin-2 (IL-2) in SLE.ObjectivesTo investigate both absolute number and percentage of CD4+CD25+Foxp3+Treg (CD4Treg) cells and effector cells on a large scale and the role of low-dose interleukin-2 (IL-2) in SLE.MethodsTwo hundred and thirty-five SLE patients (219 women and 16 men), with mean age of 37.80 ± 14.00 years, were enrolled. The absolute count and percentage of subpopulation of peripheral blood (PB) lymphocyte in these patients were measured by flow cytometry combined with internal microsphere standard. And low-dose IL-2 was used among 127 patients at a dosage of fifty WIU every day for five days. Immunological and clinical assessments were performed again at the end of IL-2 treatment. Ninety healthy volunteers, matched for patients’ age and gender, were also included for the estimation of lymphocyte subsets.ResultsAs compared to healthy controls (median of Treg cells: 33.09 cells/ul), the absolute number of circulating CD4Treg cells were significantly decreased in SLE patients (median: 15.49 cells/ul, P<0.001). The median ratios of Th17/Treg cells in patients were greatly higher than those of healthy volunteers [0.42 (0.19, 0.88) vs. 0.21 (0.15, 0.34), P<0.001], while there was not significantly different in peripheral Th17 cell between two groups. Besides, Th1, Th2, CD8+T, B cells and their respective ratios to Treg cells were like that of Th17 cells as well. Moreover, CD4Treg cells were negatively correlated with ESR and SLEDAI score (r=-0.198, P=0.01; r=-0.25, P=0.002). While no obvious correlation was seen between Th17 cells and SLEDAI score. After IL-2 therapy in SLE, there was a four-fold increase in circulating CD4Treg cells [43.73 (24.08, 74.22) vs. 11.95 (7.51, 20.34), P<0.001], whereas Th17 cells were increased slightly. The ratio of Th17/Tregs was decreased significantly in patients with IL-2 treatment [0.19 (0.09, 0.41) vs. 0.52 (0.23, 0.95), P<0.001], tended to balance and had no difference with healthy individual (P=0.275). Similarly, there were same trends in Th1, Th2, CD8+T, B and NK cells.ConclusionThe reduction of CD4Tregs but not the elevation of effector cells may be the major reason for imbalance of Teff/Treg, indicating that SLE is an autoimmune disease triggered by the defect of immunotolerance. More importantly, low-dose IL-2 might promote the proliferation of various lymphocyte subpopulation, and mainly modulated the abundance and immunosuppression activity of Tregs, which effectively induced autoimmune tolerance...

BackgroundRecent studies have reported that some drugs such as low-dose interleukin-2, rapamycin, metformin, retinoic acid and coenzyme Q10 could promote the proliferation and functional recovery of regulatory T cells (Treg) in patients with autoimmune diseases. However, the effects on the balance of Treg cells and pro-inflammatory lymphocytes and long-term efficacy have rarely been reported.ObjectivesTo evaluate the changes of peripheral lymphocyte subsets, conventional drugs and remission rate in patients with systemic lupus erythematosus (SLE) after immunomodulatory therapy.MethodsA total of 89 patients with SLE from the Second Affiliated Hospital of Shanxi Medical University from January 2016 to April 2018 were enrolled, who were divided into well-controlled group and untargeted control group taking a full consideration of the patient‘s symptoms, signs and related laboratory findings. We measured the absolute counts of B, NK, CD8+T and helper T 1 (Th1), helper T 2 (Th2), helper T 17 (Th17) and Treg cells in peripheral blood of patients before immunomodulatory therapy and during the 3 months and 6 months of follow-up and 93 sex- and age- matched control individuals using flow cytometry. Moreover, the ratios of various cells to Treg cells were calculated.ResultsCompared with healthy controls, Treg cells in SLE patients were significantly lower before the treatment with immunomodulator, while the ratios of various pro-inflammatory lymphocytes to Treg cells (such as Th2/Treg, Th17/Treg, CD8+T/Treg, etc.) were higher. After 3 months and 6 months with immunomodulatory therapy, the absolute number of Treg cells in peripheral blood of SLE patients increased obviously reaching to normal level. Accordingly, the ratios of various pro-inflammatory lymphocytes to Treg cells recovered. At the same time, the dose of glucocorticoid and disease-modifying antirheumatic drugs (DMARDs) decreased distinctly. Additionally, the well-controlled group was able to maintain a high remission rate, and the untargeted control group could achieve a higher response rate after immunomodulatory treatment.ConclusionThe imbalance between pro-inflammatory lymphocytes and Treg cells caused by the significant decrease of Treg cells may be the main cause of SLE. And immunomodulatory therapy we came up with may reverse the imbalance of proinflammatory lymphocytes and Treg cells, which is an potential and effective treatment for SLE.References[1] Chen YJ, Chang YT, Wang CB, et al. Malignancy in systemic lupus erythematosus: a nationwide cohort study in Taiwan[J]. Am J Med, 2010 Dec;123(12):1150.[2] Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory disease[J]. Autoimmun Rev, 2014, 13(6): 668-677.[3] Yu A, Snowhite I, Vendrame F, et al. Selective IL-2 responsiveness of regulatory T cells through multiple intrinsic mechanisms supports the use of low-dose IL-2 therapy in type 1 diabetes. Diabetes. 2015;64: 2172–2183.[4] Zeiser R, Leveson-Gower DB, Zambricki EA, et al. Differential impact of mammalian target of rapamycin...

Background:Rheumatoid arthritis (RA) is a progressive, irreversible disease characterized by autoimmune imbalance. Recent studies have found that the number and type of intestinal flora in RA patients were changed (called disorders), which in turn leads to immune imbalance in RA patients. The breath test can indirectly assess the growth of bacteria in the intestine. This study aimed to investigate the intestinal flora imbalance in RA patients and the effect of probiotics on the intestinal flora of RA patients using methane and hydrogen breath test.Objectives:To study the beneficial effects of probiotics on the intestinal flora of RA patients by detecting the concentrations of methane and hydrogen and the microbial populations in patients with rheumatoid arthritis (RA) before and after probiotic treatment.Methods:The lactulose methane and hydrogen breath technique were used to detect and compare the concentration of methane and hydrogen in 36 patients with RA before and after probiotic treatment (mainly Bifidobacterium, Clostridium butyricum, Lactobacillus) for 3 weeks. At the same time, the 16SRNA V3 region in stool samples of 17 patients with RA was qualitatively analyzed by Roche/45 high-throughput sequencing platform and compared with 9 healthy adult stool samples.Results:Compared with pre-intervention, after 3 weeks of probiotic treatment, the exhaled methane concentration was significantly increased in RA patients at 30 minutes, 60 minutes, and 90 minutes (P < 0.05). The sum of methane and hydrogen concentrations increased at 30 minutes (P= 0.041). There was no significant difference in hydrogen concentration before and after intervention (P > 0.05) (Table 1). Compared with healthy adults, the fecal diversity index (Shannon) of RA patients increased (P < 0.05) and the species uniformity index (flatness) also increas.Abstract THU0201 – Figure 1Conclusion:Patients with RA had a significant difference in the structure of intestinal flora compared with that of healthy controls, which may represent perturbations of microbial communities and contribute to the pathogenesis and condition of RA. Probiotics can restore the composition of the gut microbiome and introduce beneficial functions to gut microbial communities through diet, probiotics or fecal transplantation, providing a promising prospect for clinical treatment of RA.Abstract THU0201 – Figure 2References:[1] Schett I B M a G, The pathogenesis of rheumatoid arthritis. The New England Journal of Medicine, 2011. 365(23): p. Number of 2205–2219.[2] Edwards C J, Commensal gut bacteria and the etiopathogenesis of rheumatoid arthritis. J Rheumatol, 2008. 35(8): p. Number of 1477-14797.[3] Horta-Baas G, Romero-Figueroa MDS, Montiel-Jarquín AJ, Pizano-Zárate ML, García-Mena J, Ramírez-Durán N. Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis. J Immunol Res. 2017;2017:4835189Disclosure of Interests:None declared