arthroscopic-guided-synovectomy-synovial-biopsies-pathotype

Arthroscopic Guided Synovectomy, Synovial Biopsies, and Pathotype Identification in Refractory Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and joint destruction. Synovectomy and synovial biopsies ...

Shanghai Jiaotong University

We aimed to assess the influence of co-existing atopy on the prognosis of enthesitis-related arthritis (ERA). Patients diagnosed with ERA between March 2006 and August 2012 were enrolled in a prospective cohort study and followed for 2 years. Management of patients was evaluated using the American College of Rheumatology (ACR) pediatric (Pedi) 30/50/70 criteria and laboratory variables. A total of 151 ERA patients were enrolled at diagnosis and were divided into those with atopy (n = 62) and those without (n = 89). When compared with the non-atopic group, atopic patients had significantly more active joints at disease onset (4.72 vs. 3.75), more joints with limitation of motion (LOM) (1.45 vs. 0.87), more painful joints (3.61 vs. 2.80), and more swollen joints (1.02 vs. 0.69) (p < 0.05 for all comparisons). At 3, 6, 12, 18, and 24 months, fewer ERA patients with atopy reached the ACR Pedi 50 and 70 criteria (at 3 months, 25.8 vs. 60.7 % and 11.3 vs. 34.8 %, respectively; at 6 months, 50 vs. 77.5 % and 22.6 vs. 58.4 %, respectively; at 12 months, 53.2 vs. 70.8 % and 33.9 vs. 55.1 %, respectively; at 18 months, 62.9 vs. 86.5 % and 56.5 vs. 78.7 %, respectively; at 24 months, 66.1 vs. 89.9 % and 61.3 vs. 78.7 %, respectively; all p < 0.05). During the 2 years of follow-up, the number of flares was significantly higher in ERA patients with co-existing atopy (1.48 vs. 0.70, p < 0.05).

Atopy in children with the enthesitis-related arthritis (ERA) subtype of juvenile idiopathic arthritis is associated with a worse outcome.

We wished to determine the prevalence of fever as one of the first symptoms of the enthesitis-related arthritis (ERA) subtype of juvenile idiopathic arthritis. Also, we wished to ascertain if ERA patients with fever at disease onset differed from those without fever.

Fever as an initial manifestation of enthesitis-related arthritis subtype of juvenile idiopathic arthritis: retrospective study.

To investigate the effect of allergic rhinitis (AR) and its intervention on disease condition and medications in patients with juvenile-onset systemic lupus erythematosus (JSLE).

[Effect of allergic rhinitis on disease condition and treatment in patients with juvenile-onset systemic lupus erythematosus].

The influence of co-existing atopy on the prognosis of juvenile systemic lupus erythematosus (JSLE) was assessed in this study. Patients diagnosed with JSLE between October 2005 and April 2016 were enrolled in a prospective study and followed up for 2 years. Management of patients was evaluated using the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) score and laboratory variables. Eighty JSLE patients were enrolled at diagnosis and divided into those with (n = 35) and without (n = 45) atopy. When compared with the non-atopic group, atopic patients showed higher SLEDAI-2K score at disease onset (16.09 vs. 11.18), higher erythrocyte sedimentation rate (52.89 vs. 38.27 mm/h), higher percentage of total B-cells (25.85 vs. 19.51%), lower percentage (7.26 vs. 9.03%) and cytotoxicity (9.92 vs. 11.32%) of natural killer cells, and lower complement C3 (0.51 vs. 0.69 g/L) (all p<0.05). At 1, 3, 6, 12, 18, and 24 months, JSLE patients with atopy reached higher SLEDAI-2K score and lower ΔSLEDAI-2K improvement rate (at 1 month, 8.34 vs. 4.71 and 43.63 vs. 57.95%, respectively; at 3 months, 8.57 vs. 2.62 and 48.39 vs. 75.10%, respectively; at 6 months, 6.91 vs. 2.38 and 53.59 vs. 77.26%, respectively; at 12 months, 4.71 vs. 1.80 and 69.54 vs. 84.10%, respectively; at 18 months, 4.66 vs. 2.02 and 68.14 vs. 82.93%, respectively; at 24 months, 8.57 vs. 2.62 and 70.00 vs. 81.88%, respectively; all p<0.05). During the 24 months of follow-up, the total number of disease flares was higher in JSLE patients with co-existing atopy (3.77 vs. 1.51, p<0.05), and the atopic group needed much more time to reach the stable condition of the disease (6.88 vs. 4.65 months, p<0.05). JSLE patients combined with co-existing atopy had more severe disease at diagnosis and poorer outcomes than JSLE patients without atopy.

Atopy in children with juvenile systemic lupus erythematosus is associated with severe disease.

Neutrophil extracellular traps (NETs) are known to play an important role in systemic lupus erythematosus (SLE) by triggering innate and adaptive immune responses. The molecular mechanisms responsible for their formation in SLE are still unclear. In this study, we aim to characterize the role of the receptor-interacting protein kinase-1 (RIPK1), a homologous serine/threonine kinase previously implicated in the regulation of necroptosis and tissue injury, in decreasing neutrophil death and formation of NETs, and to investigate the clinical implications of RIPK1 in SLE.

A Role for Receptor-Interacting Protein Kinase-1 in Neutrophil Extracellular Trap Formation in Patients with Systemic Lupus Erythematosus: a Preliminary Study.

This study aimed to investigate the distributions of lymphocytes in adult onset Still's disease (AOSD) with liver dysfunction, and further prospectively explore whether receptor interacting serine/threonine kinases (RIPKs) in lymphocytes play a role in the pathogenesis of AOSD especially liver involvement.

The Role of RIPK1/3 in Adult Onset Still's Disease Patients With Liver Damage: A Preliminary Study.

The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16 s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free (GF) mice.

Lupus gut microbiota transplants cause autoimmunity and inflammation.

Rheumatoid arthritis (RA) is a common inflammatory disease and its treatment is largely limited by drug ineffectiveness or severe side effects. In RA progression, multiple signalling pathways, such as hypoxia-inducible factor (HIF)-1α, nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) pathways, act synergistically to maintain the inflammatory response. To downregulate HIF-1α, NF-κB, and MAPK expression, we proposed HIF-1α siRNA-loaded calcium phosphate nanoparticles encapsulated in apolipoprotein E3-reconstituted high-density lipoprotein (HIF-CaP-rHDL) for RA therapy. Here, we evaluated the potential of CaP-rHDL nanoparticles in RA therapy using a murine macrophage line (RAW 264.7) and a collagen-induced arthritis (CIA) mouse model. The CaP-rHDL nanoparticles showed significant anti-inflammatory effects along with HIF-1α knockdown and NF-κB and MAPK signalling pathway inhibition in lipopolysaccharide-activated macrophages. Moreover, they inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation. In CIA mice, their intravenous administration resulted in high accumulation at the arthritic joint sites, and HIF-CaP-rHDL effectively suppressed inflammatory cytokine secretion and relieved bone erosion, cartilage damage, and osteoclastogenesis. Thus, HIF-CaP-rHDL demonstrated great potential in RA precision therapy by inhibiting multiple inflammatory signalling pathways.

CaP-based anti-inflammatory HIF-1α siRNA-encapsulating nanoparticle for rheumatoid arthritis therapy.

This study aimed to analyse the immune cell profiles of adult-onset Still's disease (AOSD) and to stratify disease-associated endotypes.

AOSD endotypes based on immune cell profiles: patient stratification with hierarchical clustering analysis.

Glucocorticoids (GCs) are the most effective and commonly used drugs for the treatment of systemic lupus erythematosus (SLE). However, a large number of side effects occur after long-term or high-dose glucocorticoid treatment, which severely restricts the use of glucocorticoids. Reconstituted high-density lipoprotein (rHDL), an emerging nanocarrier, is promising for targeted delivery to sites of inflammation and macrophages. Here, we prepared a steroid-loaded recombinant high-density lipoprotein and evaluated its therapeutic efficacy in a murine macrophage cell line (RAW264.7) and a lupus (MRL/lpr mice) mouse model. The obtained corticosteroid-loaded nanomedicine, named PLP-CaP-rHDL, exhibited desirable characteristics. Pharmacodynamics studies revealed that the nanoparticles could significantly reduce the levels of inflammatory cytokines in the macrophages in vitro and also effectively alleviate lupus nephritis in MRL/lpr mice without causing obvious side effects at a dose of 0.25 mg/kg. Thus, our newly developed steroid-loaded rHDL nanocarriers hold a great potential for anti-inflammatory therapy with reduced side effects and may provide a precise targeted therapy for SLE.

Steroid-loaded reconstituted high-density lipoprotein nanocarrier: A new treatment for systemic lupus erythematosus.

This study aimed to elucidate the immune status of systemic lupus erythematosus (SLE) patients with infections. We enrolled 253 SLE patients including 77 patients with infections. Clinical features and immunological parameters were analyzed, with particular reference to neutrophil CD64 (nCD64) expression, myeloid-derived suppressor cells (MDSCs), activated T cells and multiple cytokines. Among the 77 SLE patients with infections, 32 patients (41.56%) developed fever and 20 patients (25.97%) developed serositis, which were higher compared to the non-infection group. A considerably higher level of nCD64 was found in the infection group (4.65 vs 1.01, P < 0.001). In addition, the infection group exhibited higher percentages of total MDSCs (6.99 vs 4.30%, P = 0.003), polymorphonuclear MDSCs (PMN-MDSCs) (P = 0.032) and monocytic MDSCs (M-MDSCs) (P = 0.015). T cells were more activated during infections, with an elevated level of IL-2R (P < 0.001). Specifically, higher percentages of CD4CD38 T cells (55.73 vs 50.17%, P = 0.036), CD8HLA-DR T cells (59.82 vs 47.99%, P < 0.001) and CD8CD38 T cells (68.59 vs 63.90%, P = 0.044) were identified in the infection group. Furthermore, the serum levels of IL-6, IL-8 and IL-10 were elevated in the infection group (all P < 0.001). Higher proportions of neutrophils, CD4 and CD8 T cells, and MDSCs were activated during infections in SLE patients. Additionally, the serum cytokines altered during infections, with noticeably elevated levels of IL-6, IL-8 and IL-10. Infections may lead to the amplification of immune alterations in SLE.

Article	Year
Atopy in children with the enthesitis-related arthritis (ERA) subtype of juvenile idiopathic arthritis is associated with a worse outcome. European journal of pediatrics\| PubMed ID: 25935591	2015
Fever as an initial manifestation of enthesitis-related arthritis subtype of juvenile idiopathic arthritis: retrospective study. PloS one\| PubMed ID: 26030261	2015
[Effect of allergic rhinitis on disease condition and treatment in patients with juvenile-onset systemic lupus erythematosus]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics\| PubMed ID: 28506339	2017
Atopy in children with juvenile systemic lupus erythematosus is associated with severe disease. PloS one\| PubMed ID: 28545118	2017
A Role for Receptor-Interacting Protein Kinase-1 in Neutrophil Extracellular Trap Formation in Patients with Systemic Lupus Erythematosus: a Preliminary Study. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology\| PubMed ID: 29550813	2018
The Role of RIPK1/3 in Adult Onset Still's Disease Patients With Liver Damage: A Preliminary Study. Frontiers in immunology\| PubMed ID: 33329521	2020
Lupus gut microbiota transplants cause autoimmunity and inflammation. Clinical immunology (Orlando, Fla.)\| PubMed ID: 34813937	2021
CaP-based anti-inflammatory HIF-1α siRNA-encapsulating nanoparticle for rheumatoid arthritis therapy. Journal of controlled release : official journal of the Controlled Release Society\| PubMed ID: 35085700	2022
AOSD endotypes based on immune cell profiles: patient stratification with hierarchical clustering analysis. Rheumatology (Oxford, England)\| PubMed ID: 35972374	2023
Steroid-loaded reconstituted high-density lipoprotein nanocarrier: A new treatment for systemic lupus erythematosus. Journal of biomaterials applications\| PubMed ID: 36869874	2023
Immune profile alterations of systemic lupus erythematosus patients with infections. Clinical and experimental medicine\| PubMed ID: 37938465	2023

Ruru Guo

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