Chemokine Profile in the Sera and Urine of Patients with Schistosomal Glomerulopathy

Otoni, Alba; Teixeira, Antônio Lúcio; Voieta, Izabela; Antunes, Carlos Maurício de Figueiredo; Melo, Vinícius Lins Costa; Drummond, Sandra; Rodrigues, Valério Ladeira; Lambertucci, José Roberto

doi:10.4269/ajtmh.13-0270

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…This current study restricted only to BPH patients negative for prostate cancer, as determined by prostate biopsy, found that increasing urine levels of CXCL‐10, CCL5, and CCL3 were marginally associated with the extent of inflammation and greater intensity of CD3 and CD20 lymphocytic infiltration in prostate tissue. Previous studies have reported that urine levels of CXCL‐10, CCL3, and CCL5 in healthy male asymptomatic control subjects are either undetectable or below the median values of BPH subjects reported here and elsewhere …”

Section: Discussionmentioning

confidence: 38%

“…Previous studies have reported that urine levels of CXCL-10, CCL3, and CCL5 in healthy male asymptomatic control subjects are either undetectable or below the median values of BPH subjects reported here and elsewhere. 20,22 One of the predisposing factor for BPH is the metabolic syndrome, 10 whose key determinant is the increased centralized deposition of adipose tissue. We found a broad and robust relationship between a key measure of centralized adiposity called waist-hip ratio and increased urine levels of sIL-1Ra.…”

Section: Discussionmentioning

confidence: 99%

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Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients

et al. 2017

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Purpose: Benign prostatic hyperplasia (BPH) is strongly associated with obesity and prostatic tissue inflammation, but the molecular underpinning of this relationship is not known. Here, we examined the association between urine levels of chemokines/ adipokines with histological markers of prostate inflammation, obesity, and lower urinary tract symptoms LUTS in BPH patients. Methods: Frozen urine specimens from 207 BPH/LUTS patients enrolled in NashvilleMen's Health Study were sent for blinded analysis of 11 analytes, namely sIL-1RA, CXC chemokines (CXCL-1, CXCL-8, CXCL-10), CC chemokines (CCL2, CCL3, CCL5), PDGF-BB, interleukins IL-6, IL-17, and sCD40L using Luminex™ xMAP® technology.After adjusting for age and medication use, the urine levels of analytes were correlated with the scales of obesity, prostate inflammation grade, extent, and markers of lymphocytic infiltration (CD3 and CD20) using linear regression.Results: sIL-1RA levels were significantly raised with higher BMI, waist circumference and waist-hip ratio in BPH patients after correction for multiple testing (P = 0.02). Men with greater overall extent of inflammatory infiltrates and maximal CD3 infiltration were marginally associated with CXCL-10 (P = 0.054) and CCL5 (P = 0.054), respectively. CCL3 in 15 patients with moderate to severe grade inflammation was marginally associated with maximal CD20 infiltration (P = 0.09), whereas CCL3 was undetectable in men with mild prostate tissue inflammation.There was marginal association of sCD40L with AUA-SI scores (P = 0.07).Conclusions: Strong association of sIL-1RA in urine with greater body size supports it as a major molecular correlate of obesity in the urine of BPH patients. Increased urine levels of CXCL-10, CCL5, and CCL3 were marginally associated with the scores for prostate tissue inflammation and lymphocytic infiltration. Overall, elevated urinary chemokines support that BPH is a metabolic disorder and suggest a molecular link between BPH/LUTS and prostatic inflammation. K E Y W O R D S BPH, inflammation, obesity, urineThe Prostate. 2018;78:17-24.wileyonlinelibrary.com/journal/pros

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Section: Discussionmentioning

confidence: 38%

Section: Discussionmentioning

confidence: 99%

Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients

et al. 2017

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“…Consequently, the severity of the disease is directly related to the worm burden and the inflammatory response to deposited eggs ( 67 ). For instance, as recently reviewed ( 68 ), the chemokines CCL2, CCL3, and CCL4 correlate with the severity of S. mansoni , where CCL3 is related to the recruitment of eosinophils and induction of granulomatous pathology ( 69 ), while CCL2 is associated with glomerulopathy ( 70 ). A more “traditional” vaccine concept would target a reduction of the worm number or even prevent infection.…”

Section: Discussionmentioning

confidence: 99%

Protective Potential of Antioxidant Enzymes as Vaccines for Schistosomiasis in a Non-Human Primate Model

et al. 2015

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Schistosomiasis remains a major cause of morbidity in the world. The challenge today is not so much in the clinical management of individual patients, but rather in population-based control of transmission in endemic areas. Despite recent large-scale efforts, such as integrated control programs aimed at limiting schistosomiasis by improving education and sanitation, molluscicide treatment programs and chemotherapy with praziquantel, there has only been limited success. There is an urgent need for complementary approaches, such as vaccines. We demonstrated previously that anti-oxidant enzymes, such as Cu–Zn superoxide dismutase (SOD) and glutathione S peroxidase (GPX), when administered as DNA-based vaccines induced significant levels of protection in inbred mice, greater than the target 40% reduction in worm burden compared to controls set as a minimum by the WHO. These results led us to investigate if immunization of non-human primates with antioxidants would stimulate an immune response that could confer protection as a prelude study for human trials. Issues of vaccine toxicity and safety that were difficult to address in mice were also investigated. All baboons in the study were examined clinically throughout the study and no adverse reactions occurred to the immunization. When our outbred baboons were vaccinated with two different formulations of SOD (SmCT-SOD and SmEC-SOD) or one of GPX (SmGPX), they showed a reduction in worm number to varying degrees, when compared with the control group. More pronounced, vaccinated animals showed decreased bloody diarrhea, days of diarrhea, and egg excretion (transmission), as well as reduction of eggs in the liver tissue and in the large intestine (pathology) compared to controls. Specific IgG antibodies were present in sera after immunizations and 10 weeks after challenge infection compared to controls. Peripheral blood mononuclear cells, mesenteric, and inguinal node cells from vaccinated animals proliferated and produced high levels of cytokines and chemokines in response to crude and recombinant antigens compared with controls. All together, these data demonstrate the potential of antioxidants as a vaccine in a non-human primate model.

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Urinary Biomarkers and Benign Prostatic Hyperplasia

Tyagi

Wang

Yoshimura

2019

Curr Bladder Dysfunct Rep

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Chemokine Profile in the Sera and Urine of Patients with Schistosomal Glomerulopathy

Cited by 4 publications

References 31 publications

Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients

Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients

Protective Potential of Antioxidant Enzymes as Vaccines for Schistosomiasis in a Non-Human Primate Model

Urinary Biomarkers and Benign Prostatic Hyperplasia

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