scholarly journals Interleukin-17A blockade with secukinumab results in decreased neutrophil infiltration in psoriasis: minimally-invasive measurement by tape stripping

2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Christian Loesche ◽  
Frank Kolbinger ◽  
Marie-Anne Valentin ◽  
Philip Jarvis ◽  
Melanie Ceci ◽  
...  

Psoriasis is a well characterized interleukin (IL)-17A-driven skin disease with neutrophil infiltration and epidermal hyperkeratosis. Several biomarkers, most prominently β-defensin-2 (BD-2), have been identified using local and systemic invasive measurements as responsive markers of IL-17A-driven skin pathology. We sought to determine whether measurements of epidermal proteins by tape stripping could offer a minimally-invasive method to assess treatment responses. We compared the expression of 170 proteins in the epidermis (tape stripping) and dermis (open flow microperfusion) of 8 psoriatic subjects before and after administration of a single dose of subcutaneous (s.c.) antiIL-17A mAb secukinumab. Proteomic analyses of tape strips revealed a >3-fold decrease in 32 epidermal and inflammatory cell proteins in response to secukinumab. The epidermal proteins with the largest (>10-fold) decreases were: matrix metalloproteinase-8 (MMP-8, 15.68-fold, p<0.05); myeloperoxidase (MPO, 14.72-fold, p<0.005); IL-8 (11.93-fold, p<0.05); MMP-9 (10.81-fold, p<0.005); and IL-1β (10.35-fold, p<0.05). For these proteins, greater-fold protein changes were detected in the epidermis compared to dermis. Immunohistochemical analysis confirmed that neutrophils are the predominant cell type in psoriatic skin lesions that express MPO, MMP-8 and MMP-9, and that secukinumab treatment dramatically decreases neutrophil accumulation. Thus, tape stripping may be used to assess epidermal neutrophils, and protein biomarker responses to anti-IL-17A therapy in psoriasis.

2015 ◽  
Vol 129 (9) ◽  
pp. 870-873
Author(s):  
C R Kieliszak ◽  
T R Khoury ◽  
A Singh ◽  
A S Joshi

AbstractObjectives:This study assessed the utility of current sialendoscopes in the paranasal sinuses in a cadaveric model and evaluated novel uses for sialendoscopes.Methods:Currently available sialendoscopes were used for visualisation and performing interventions in the paranasal sinuses. Ten cadaver heads were studied before and after dissection. Outcomes included ostia identification, sinus cannulation, success of mucosal biopsy collection and image clarity.Results:Marchal and Erlangen sialendoscopes were found to be effective for both visualising and cannulating the sphenoid sinuses before and after dissection. Both types demonstrated poor maxillary ostia visualisation without dissection, but did allow treatment after antrostomy. Larger diameter sialendoscopes were associated with the lowest image distortion during maxillary ostia assessment. Mucosal biopsy collection within the sphenoid sinus, but not in the maxillary sinus, was possible before dissection.Conclusion:Sialendoscopes can be used for visualisation and performing interventions in the sinonasal cavity, but their utility is mainly limited to the sphenoid sinus. They may be considered a minimally invasive method for drug delivery and/or biopsy collection in the post-operative setting for all sinuses. Design improvements are suggested.


Rheumatology ◽  
2018 ◽  
Vol 58 (4) ◽  
pp. 617-627 ◽  
Author(s):  
Sijia Chen ◽  
Troy Noordenbos ◽  
Iris Blijdorp ◽  
Leonieke van Mens ◽  
Carmen A Ambarus ◽  
...  

Abstract Objectives Synovial mast cells contain IL-17A, a key driver of tissue inflammation in SpA. A recent in vitro study showed that tissue-derived mast cells can capture and release exogenous IL-17A. The present study aimed to investigate if this mechanism could contribute to tissue inflammation in SpA. Methods Potential activation of mast cells by IL-17A was assessed by gene expression analysis of the Laboratory of Allergic Diseases 2 (LAD2) mast cell line. The presence of IL-17A-positive mast cells was assessed by immunohistochemistry in synovial tissue obtained before and after secukinumab treatment, as well as in skin and gut tissues from SpA-related conditions. Results IL-17A did not induce a pro-inflammatory response in human LAD2 mast cells according to the canonical IL-17A signalling pathway. In SpA synovial tissue, the percentage of IL-17A-positive mast cells increased upon treatment with secukinumab. IL-17A-positive mast cells were also readily detectable in non-inflamed barrier tissues such as skin and gut. In non-inflamed dermis and gut submucosa, IL-17A-positive mast cells are the most prevalent IL-17A-positive cells in situ. Compared with non-inflamed tissues, both total mast cells and IL-17A-positive mast cells were increased in psoriatic skin dermis and in submucosa from inflammatory bowel disease gut. In contrast, the proportion of IL-17A-positive mast cells was strikingly lower in the inflamed compared with non-inflamed gut lamina propria. Conclusion IL-17A-positive mast cells are present across SpA target tissues and correlate inversely with inflammation, indicating that their IL-17A content can be regulated. Tissue-resident mast cells may act as IL-17A-loaded sentinel cells, which release IL-17A to amplify tissue inflammation.


2018 ◽  
Vol 86 (6) ◽  
pp. 1447-1456
Author(s):  
ENAS S. MOHAMMED, M.Sc.; MONA A. ATWA, M.D. ◽  
SAHAR F. MANSOUR, M.D.; NADER A. ISMAIL, M.D.

2017 ◽  
Vol 20 (4) ◽  
pp. 227-231
Author(s):  
Evgeny Yu. Evdokimov ◽  
A. V Sundukov

Clinical and laboratory evaluation of the effectiveness of therapy of psoriasis vulgaris in 78 HIV-infected patients using the two treatment regimens is presented. Peculiarities of clinical course of psoriasis depending on the number of CD4+lymphocytes in the peripheral blood are shown. Histological and histochemical studies of biopsy samples from psoriatic skin lesions and apparently healthy skin in 15 people were performed. The dynamics before and after treatment of CD4+ and CD8+ lymphocytes in biopsies of skin and blood, their relationship with the index of severity of psoriasis (PASI) are presented. This study is of theoretical and practical interest in understanding the value and role of CD4+ and CD8+ lymphocytes in the formation of inflammatory reactions in the skin of patients with psoriasis as a possible option for treatment of psoriasis in HIV-infected patients.


2000 ◽  
Vol 143 (5) ◽  
pp. 950-956 ◽  
Author(s):  
C. Miracco ◽  
M. Pellegrino ◽  
M.L. Flori ◽  
R. Vatti ◽  
M. Materno ◽  
...  

2012 ◽  
Vol 3 (1) ◽  
pp. 20-22
Author(s):  
Dr. Dhaval J Patel ◽  
◽  
Dr. Bipin B Chhajed ◽  
Dr. Dhaval R Modi ◽  
Dr. Nirav P Trivedi ◽  
...  

Author(s):  
Anton Yarikov ◽  
Maxim Shpagin ◽  
Iliya Nazmeev ◽  
Sergey Gorelov ◽  
Olga Perlmutter

The immediate and long-term results of treatment of 30 patients with severe pain syndrome of the lumbar region, who underwent operations on denervation of DOS, were studied. The aim of the study was to evaluate the effectiveness of minimally invasive technologies for the treatment of pain in the lumbar region (denervation of DOS), to study the near and distant results of these treatment methods. Denervation DOS is an effective minimally invasive method for the treatment of facet syndrome caused by spondylarthrosis. It allows in the early and distant postoperative periods to significantly reduce the pain syndrome and improve the quality of life of patients.


Author(s):  
Patrick Veit-Haibach ◽  
Martin W. Huellner ◽  
Martin Banyai ◽  
Sebastian Mafeld ◽  
Johannes Heverhagen ◽  
...  

Abstract Objectives The purpose of this study was the assessment of volumetric CT perfusion (CTP) of the lower leg musculature in patients with symptomatic peripheral arterial disease (PAD) before and after interventional revascularisation. Methods Twenty-nine consecutive patients with symptomatic PAD of the lower extremities requiring interventional revascularisation were assessed prospectively. All patients underwent a CTP scan of the lower leg, and hemodynamic and angiographic assessment, before and after intervention. Ankle-brachial pressure index (ABI) was determined. CTP parameters were calculated with a perfusion software, acting on a no outflow assumption. A sequential two-compartment model was used. Differences in CTP parameters were assessed with non-parametric tests. Results The cohort consisted of 24 subjects with an occlusion, and five with a high-grade stenosis. The mean blood flow before/after (BFpre and BFpost, respectively) was 7.42 ± 2.66 and 10.95 ± 6.64 ml/100 ml*min−1. The mean blood volume before/after (BVpre and BVpost, respectively) was 0.71 ± 0.35 and 1.25 ± 1.07 ml/100 ml. BFpost and BVpost were significantly higher than BFpre and BVpre in the treated limb (p = 0.003 and 0.02, respectively), but not in the untreated limb (p = 0.641 and 0.719, respectively). Conclusions CTP seems feasible for assessing hemodynamic differences in calf muscles before and after revascularisation in patients with symptomatic PAD. We could show that CTP parameters BF and BV are significantly increased after revascularisation of the symptomatic limb. In the future, this quantitative method might serve as a non-invasive method for surveillance and therapy control of patients with peripheral arterial disease. Key Points • CTP imaging of the lower limb in patients with symptomatic PAD seems feasible for assessing hemodynamic differences before and after revascularisation in PAD patients. • This quantitative method might serve as a non-invasive method, for surveillance and therapy control of patients with PAD.


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