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Msg  34251 of 34484  at  5/2/2021 2:15:34 PM  by

moneyonomics

The following message was updated on 5/3/2021 12:34:13 AM.

Repost "Encouraging for NAV3-32 trial: CD206 expressing neutrophils investigated-CD206 observed in small sampling JIA (Juvenile Arthritis) synovial tissue biopsies...Sweden 2021"

  The following message was updated on 2/23/2021 12:04:54 PM.

Encouraging for NAV3-32 trial: CD206 expressing neutrophils investigated-CD206 observed in small sampling JIA (Juvenile Arthritis) synovial tissue biopsies ...Sweden 2021

         

A small 4 patient and a more superficial study than NAV 3-32, but still appears to provide some useful and intriguing early CD206 synovial tissue observations. 

 

 

“….Synovial fluid was obtained from knee in all patients. Blood and synovial fluid during active arthritis were collected from 17 patients. Synovial tissue biopsies were obtained from four patients, one of which is not included in phenotype or function analyses due to ongoing treatment with methotrexate (patient no 18), in conjunction with synovial fluid aspiration. Follow-up blood samples from periods of inactive disease were collected from six of the patients. During periods of inactive disease some of the patients were treated with conventional or biologic disease-modifying antirheumatic drugs (DMARD). Patient characteristics are described in table 1. Twelve of the patients were also included in a previous study (25), indicated in table 1…..

 

…..To confirm the finding of CD206+ neutrophils in synovial fluid we investigated whether neutrophils migrating through synovial tissue express CD206. Synovial tissue biopsies obtained from four patients were stained for CD206 and myeloperoxidase (MPO). Neutrophils co-expressing both MPO and CD206 were observed in tissue biopsies from patient 4, 8 and 18 (Figure 2, arrows), demonstrating that CD206-expressing neutrophils can be present in synovial tissue. In all biopsies there were also neutrophils without CD206 expression (Figure 2, arrow heads). In two of biopsies we observed synovial blood vessels, and the circulating neutrophils within the vessels had no or low CD206 expression (Figure 2B-C). The biopsy from patient 17 did not contain any area with neutrophils (data not shown)…..”

 


https://www.researchsquare.com/article/rs-200749/v1



Synovial Fluid Neutrophils in Oligoarticular Juvenile Idiopathic Arthritis Have an Altered Phenotype and Impaired Effector Functions

Sabine Arve-Butler Lund University: Lunds UniversitetTobias Schmidt Lund University: Lunds UniversitetAnki Mossberg Lund University: Lunds UniversitetElisabet Berthold Lund University: Lunds UniversitetBirgitta Gullstrand Lund University: Lunds UniversitetAnders A Bengtsson Lund University: Lunds UniversitetFredrik Kahn Lund University: Lunds UniversitetRobin Kahn

 

 
 

Abstract

Background

Neutrophils are the most prevalent immune cells in synovial fluid in inflamed joints of children with oligoarticular juvenile idiopathic arthritis (JIA).

 

Despite this, little is known about neutrophil function at the site of inflammation in JIA and how local neutrophils contribute to disease pathogenesis. This study aimed to characterize phenotype and function of synovial fluid neutrophils in oligoarticular JIA.

 

Methods

Neutrophils obtained from paired blood and synovial fluid from patients with active oligoarticular JIA were investigated phenotypically (n=17) and functionally (phagocytosis and oxidative burst, n=13) by flow cytometry. In a subset of patients (n=6), blood samples were also obtained during inactive disease at a follow-up visit. Presence of CD206-expressing neutrophils was investigated in synovial biopsies from four patients by Immune florescence.

 

Results

Neutrophils in synovial fluid had an activated phenotype, characterized by increased CD66b and CD11b levels, and most neutrophils had a CD16hi CD62Llow aged phenotype. A large proportion of the synovial fluid neutrophils expressed CD206, a mannose receptor not commonly expressed by neutrophils but by monocytes, macrophages and dendritic cells. CD206 expressing neutrophils were also found in synovial tissue biopsies. The synovial fluid neutrophil phenotype was not dependent on transmigration alone. Functionally, synovial fluid neutrophils had reduced phagocytic capacity and a trend towards impaired oxidative burst compared to blood neutrophils. In addition, the effector functions of the synovial fluid neutrophils correlated negatively with the proportion of CD206+ neutrophils.

 

 

Conclusions

Neutrophils in the inflamed joint in oligoarticular JIA were altered, both regarding phenotype and function. Neutrophils in the synovial fluid were activated, had an aged phenotype, had gained monocyte-like features and had impaired phagocytic capacity. The impairment in phagocytosis and oxidative burst was associated to the phenotype shift. We speculate that these neutrophil alterations might play a role in the sustained joint inflammation seen in JIA.

 

 



 
 
 
 
 
 
 
 
 
 
Msg  33838 of 34250  at  2/22/2021 9:55:17 PM  by

moneyonomics

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