Cytokine and LL-37 gene expression levels in Bartonella spp. seropositive and seronegative patients of a rheumatology clinic

PurposeThe variation in the immune response to Bartonella spp. infection in humans remains unclear. The present study compares the expression of selected interleukins, cytokines and cathelicidin (LL-37) in rheumatology clinic patients suffering from musculoskeletal symptoms with healthy blood donors. The patients had previously been tested for the presence of Bartonella henselae antibodies.MethodsGene expression of LL-37, interleukin (IL)-2, IL-4, IL-6, IL-12, interferon-(IFN)-γ, and tumor necrosis factor (TNF-α)-α was determined in blood samples using quantitative Polymerase Chain Reaction (qPCR). Statistical analysis was prepared with STATISTICA.ResultsStatistically significant differences in the mRNA levels of the tested cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-12; p<0.0001) were observed between the healthy controls and patients; however, no difference was observed for LL37 mRNA (p ?= ?0.1974). No significant differences in mRNA expression were observed between IgG in anti-Bartonella seropositive and seronegative individuals (p>0.05). The only significant differences between the Bartonella spp. DNA positive and negative patients, indicated by PCR, were observed for TNF-α and IL-12 mRNA (p ?= ?0.0045 and p ?= ?0.0255, respectively).ConclusionA broadly similar immune response to the tested cytokines was observed among the participants irrespective of anti-Bartonella spp. IgG seropositivity. However, the Bartonella DNA-positive participants demonstrated significantly lower expression of IL-12 and TNF-α mRNA; this may indicate that these bacteria have a suppressive influence on the immune system.     

Correlation of 3-T MRI and CT findings with patient symptoms and treatment outcome in radiofrequency ablation of osteoid osteoma

ObjectiveThe aim of this prospective study was to evaluate pre- and post-treatment MRI and CT findings of osteoid osteoma (OO) patients treated with radiofrequency thermo-ablation (RFTA) and to compare these findings with visual analog scale (VAS) scores.MethodsSixteen patients (4 females and 12 males; mean age of 18.87 ± 8.75 years (range: 8–37)) with OO were examined with CT and MRI, at baseline and at an average of 3 months following the procedure. On pre- and post-procedural CT and MRIs, OO-related findings were recorded. Treatment success was evaluated with VAS scores.ResultsBaseline VAS scores were 8 or 9 and follow-up scores were 0 or 1, indicating no early recurrences.Nidus diameters decreased significantly after the procedure (p = 0.027, p = 0.002, and p = 0.002; and p = 0.001, p = 0.001, p = 0.001 for AP, ML and CC nidus diameters for CT and MRI, respectively).The mean nidus volume were significantly decreased after the procedure (p = 0.001, for CT and MRI).On post-procedural images, cortical thickening, the signal intensity and contrast enhancement of the nidus and the extent of periostitis were significantly decreased (p = 0.019, p = 0.001, p = 0.001 and p = 0.034, respectively). There was no significant change in nidus calcification, perinidal cortical and intramedullary sclerosis, periosteal reaction, bone deformity, bone marrow and soft tissue edema, joint effusion and synovitis after the procedure (p = 0.253, p = 0.062, p = 0.245, p = 1, p = 1, p = 0.429, p = 0.371, p = 0.625, p = 1).ConclusionAlthough the changes in imaging findings may be helpful in early follow-up of OO patients treated with RFTA, these changes alone cannot be used with accuracy in predicting treatment response.Level of EvidenceLevel IV, Therapeutic Study.     

白细胞介素35和白细胞介素37与结直肠癌临床病理学特征及预后的相关性研究

背景与目的：结直肠癌（colorectal cancer，CRC）为世界第三常见恶性肿瘤，近年来研究者认为白细胞介素（interleukin，IL）-35和（或）IL-37与CRC的发展有关，但其作用机制尚未阐明。探究IL-35和IL-37在CRC发展中的作用及其可能的机制，分析IL-35和IL-37与CRC患者预后的相关性。方法：收集2013年—2017年在上海交通大学医学院附属同仁医院接受治疗的191例CRC患者手术病理蜡块的肿瘤组织，与其匹配的非癌组织是来源于同一患者的肠癌手术切缘蜡块组织。应用免疫组织化学（immunohistochemistry，IHC）染色法将CRC患者的癌组织与非癌组织染色，并运用Image-Pro Plus将IHC染色阳性部分定量分析，结合随访结果，探讨癌组织与非癌组织中IL-35和IL-37的表达水平与CRC临床病理学特征及预后的相关性。结果：与非癌组织相比，CRC组织中IL-35的表达量减少了50%（P<0.000 1）。CRC组织中IL-37的表达量与非癌组织相比增加了40%（P=0.012）。多因素生存分析显示，癌组织中IL-35（HR=0.39；95% CI：0.16~0.97；P=0.04）的表达水平是CRC患者术后生存的独立预测指标。结论：IL-35和IL-37蛋白的表达水平可能与CRC的发展有关，IL-35的表达水平可能是CRC患者术后生存的独立预测指标。     

Secretion,blood levels and cutaneous expression of TL1A in psoriasis patients

TL1A is a TNF‐like cytokine which has been shown to co‐stimulate TH1 and TH17 responses during chronic inflammation. The expression of this novel cytokine has been investigated in inflammatory disorders like rheumatoid arthritis and inflammatory bowel disease, but little is known about expression and induction in psoriasis. Indeed, the pathogenesis in psoriasis is still not fully understood and it is speculated that cytokines other than TNF‐α are important in subsets of patients. Also, for patients with severe disease that are treated with systemic anti‐TNF‐α blockade, novel candidates to be used as disease and response biomarkers are of high interest. Here, we demonstrate TL1A expression in biopsies from psoriatic lesions. Also, we investigated spontaneous and induced TL1A secretion from PBMCs and blood levels from a cohort of psoriasis patients. Here, increased spontaneous secretion from PBMCs was observed as compared to healthy controls and a small subset of patients had highly elevated TL1A in the blood. Interestingly, activation of PBMCs with various cytokines showed a decreased sensitivity for TL1A activation in psoriasis patients compared to healthy controls.TL1A levels in blood and biopsies could not be correlated with disease activity with this patient cohort. Thus, additional large‐scale studies are warranted to investigate TL1A as a biomarker.     

Elevated serum levels of Interleukin‐37 are associated with inflammatory cytokines and disease activity in rheumatoid arthritis

Interleukin‐37 (IL‐37) is closely associated with several inflammatory diseases. However, the role of IL‐37 in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The aim of this study was to assess the associations between serum levels of IL‐37 and disease activity, inflammatory cytokines, and bone loss in patients with RA. Serum cytokines levels were examined by Enzyme‐linked immunosorbent assay (ELISA). Radiographic bone erosion was assessed using the van der Heijde‐modified Sharp score and bone mineral density (BMD) was measured using DXA. Serum IL‐37 levels in RA patients were significantly higher than those in HCs (p < 0.001), and were significantly positively correlated with clinical parameters of disease activity and serum levels of IL‐17 and IL‐23. In addition, serum IL‐37 levels were significantly higher in patients with stage IV of radiographic bone erosion than those with stage III and stage I–II, and they were significantly higher in those with osteopenia and osteoporosis than in those with normal BMD. Our results suggest that serum IL‐37 levels were increased in patients with RA and were positively associated with disease activity, IL‐17/IL‐23 and bone loss in RA, suggesting that IL‐37 may play a critical role in the pathogenesis of RA.     

The balance of serum IL-18/IL-37 levels is disrupted during the development of oral squamous cell carcinoma

Growing evidences have demonstrated a pivotal role of chronic inflammation in oral squamous cell carcinoma (OSCC) through the modulation of inflammatory cells and cytokine production. IL-37 is newly discovered anti-inflammatory member of IL-1 family and can bind to IL-18 receptor to inhibit IL-18 (pro-inflammatory member of IL-1 family) function. Investigation on the balance of IL-18/IL-37 would provide new insights into the function of IL-1 family in OSCC. Thus, serum IL-18 and IL-37 levels of OSCC patients (n = 108), leukoplakia patients (n = 40), and healthy donors (n = 36) were collected to analyze the balance of IL-18 and IL-37, and also determine their diagnostic value and prognostic significance in OSCC. The results showed that OSCC patients had high IL-18 and low IL-37 levels in serum and peripheral blood mononuclear cell (PBMC). The ratio of IL-18/IL-37 in serum efficiently distinguished non-cancer individuals from OSCC patients (cut off value: 2.15). Moreover, patients with high IL-18 and low IL-37 were susceptible to develop advanced tumor stage and lymph node metastasis (Odd ratios of IL-18/IL-37 is 4.903 and 12.613, respectively). Meanwhile, higher IL-18/IL-37 ratio could predict shorter overall survival and disease-free survival of OSCC patients, although it was not an independent prognostic factor. We further analyze the correlations of serum IL-18/IL-37 with immunocytes in peripheral blood and found that high IL-18 level was associated with more CD19⁺ B cells, while serum IL-37 seem to be associated with reduced percentage of CD3⁺CD8⁺ T cells, indicating its balance could change the adaptive immune response. Unexpectedly, we first revealed the different function of IL-18/IL-37 in serum and tumor tissues. High mRNA expression of IL-18 in tumor tissues correlated with low lymph node metastasis rate and low tumor stage, which was contradictory to the pro-tumor role of IL-18 in serum. In conclusion, enhanced ratio of IL-18/IL-37 level in serum could be an efficient biomarker for OSCC. Its balance might regulate CD19⁺ B cells and CD3⁺ CD8⁺ T cells for OSCC progression.     

Maternal influenza vaccination and child mortality: Longitudinal,population-based linked cohort study

Influenza vaccination is recommended to protect mothers and their infants from influenza. Few studies have evaluated the association between maternal influenza vaccination and child mortality. We aimed to evaluate the association between in utero exposure to seasonal inactivated influenza vaccine (IIV) and mortality among young children. This longitudinal, population-based cohort study included 191,247 maternal-child pairs in Western Australia between April 2012 and December 2017. Maternal vaccine information was obtained from a state-wide antenatal vaccination database. Mortality was defined as a record of a death registration. We used Cox proportional hazard models, weighted by the inverse-probability of treatment (vaccination), to estimate the hazard ratio of child mortality associated with in utero exposure to seasonal IIV. This study found no association between in utero exposure to seasonal IIV and mortality through age five years.     

IL-37b作用于树突状细胞CD39/ATP轴抑制类风湿性关节炎大鼠炎症反应的作用及机制

目的探讨白细胞介素37b重组蛋白(rmIL-37b)通过调节CD39/ATP轴抑制树突状细胞(DC)诱导类风湿性关节炎(RA)大鼠炎症反应的机制。方法将SD大鼠随机分为空白对照组(CTL)、CIA模型组、rmIL-37b 5μg/kg组、rmIL-37b 10μg/kg组,每组各10只。除了空白对照组外,其余大鼠采用含有卡介苗的完全弗氏佐剂和牛Ⅱ型胶原混合乳液免疫刺激,建立CIA模型。确定建模成功当天(D0),rmIL-37b组分别尾静脉注射5μg/kg、10μg/kg rmIL-37b;CTL组和CIA模型组注射相同体积的(1 ml/kg)生理盐水,连续给药15 d。免疫组化法检测滑膜组织Nod样受体蛋白3(NRPL3)炎症小体的表达,流式细胞术检测DC表型,另外试剂盒检测血清三磷酸腺苷(ATP)和免疫学指标。结果与CIA模型组相比,rmIL-37b 10μg/kg组大鼠足容积、AI值、NLRP3炎症小体表达量、血清ATP、IL-1β、IL-18、肿瘤坏死因子α(TNF-α)、抗Ⅱ型胶原抗体亚型(anti-ColⅡ-IgG、anti-ColⅡ-IgG2a)水平均降低,同时DC表面CD...     

ACEMg supplementation ameliorates progressive Connexin 26 hearing loss in a child

Mutations in the gene encoding Connexin 26 are the most common cause of genetic hearing loss. The hearing loss is typically stable but may be progressive. The reason for progression is unknown. Antioxidants have been associated with attenuation of hearing loss from other insults. One antioxidant regimen consists of beta-carotene (metabolized to vitamin A), vitamin C, vitamin E, and magnesium (ACEMg). We present a child with Connexin 26 related hearing loss who experienced progressive hearing loss over 7 years of observation. He was given ACEMg daily for 3 years, during which time his progressive hearing loss was ameliorated.