Analysis of related factors for RA flares after SARS-CoV-2 infection: a retrospective study from patient survey.

SARS-CoV-2 and its variants are widely prevalent worldwide. With frequent secondary and breakthrough infections, immune dysfunction in RA patients, and long-term use of immune preparations, SARS-CoV-2 infection poses a significant challenge to patients and rheumatologists. Whether SARS-CoV-2 infection causes RA flares and what factors aggravate RA flares are poorly studied. A questionnaire survey was conducted on RA patients infected with SARS-CoV-2 after December 7, 2022, in China through a multicenter and inter-network platform regarding general personal condition, primary disease, comorbidity, SARS-CoV-2 vaccination, viral infection, and impact on the primary disease. A total of 306 RA patients were included in this study, and the patient data were analyzed, in which the general condition of RA patients, medication use before SARS-CoV-2 infection and post-infection typing and manifestations, and medication adjustment did not affect the Flare of RA patients after SARS-CoV-2 infection. The control of disease before SARS-CoV-2 infection (OR = 2.10), RA involving pulmonary lesions (OR = 2.28), and the recovery time of COVID-19 (OR = 2.50) were risk factors for RA flare. RA involving pulmonary lesions, control status of disease before infection, and recovery time of COVID-19 disease are risk factors for RA flare after SARS-CoV-2 infection.

A clinical analysis of hemophagocytic syndrome secondary to autoimmune diseases.

Objectives: This study aimed to analyze the differences of etiologies and clinical features between patients with autoimmune-associated hemophagocytic syndrome (AAHS) and those with other underlying diseases of hemophagocytic syndrome (HPS). Patients and methods: The retrospective study was performed with 130 HPS patients (70 males, 60 females; mean age: 50.4±18.1 years; range, 13 to 85 years) between January 1st, 2011, and April 1st, 2022. The patients fulfilled at least five of the eight criteria proposed by the Histiocytosis Society in 2004. The underlying diseases related to HPS were divided into four categories: autoimmune, infection, malignancy and idiopathic diseases. And the clinical manifestations, laboratory examinations, treatments, and prognosis were analyzed respectively. Results: Nineteen (14.6%) patients had AAHS, 45 (34.6%) had infection-associated HPS, 57 (43.8%) had malignancy-associated HPS, and nine (6.9%) had idiopathic HPS. The most common symptoms of HPS were unremitting fever in 123 (94.6%) of 130 patients and splenomegaly in 92 (70.8%). All patients manifested a decline of at least two lineages of hematopoietic cells. The absolute values of T cells and B cells of AAHS were significantly higher than that of malignancy-associated HPS. The levels of soluble CD25 (interleukin-2 receptor) of AAHS were the lowest among all-cause HPS (p<0.05). The all-cause mortality rate of hospitalized patients with HPS was 46.2%. The patients with AAHS had a better prognosis compared to other etiologies (odds ratio [OR]=0.091, 95% confidence interval [CI]: 0.011-0.775, p=0.028). Epstein-Barr virus infection (OR=4.761, 95% CI: 1.619-14.004, p=0.005) and pulmonary involvement (OR=4.555 95% CI: 1.524-13.609, p=0.007) were independent predictors of poor outcome in HPS. Thrombocytopenia (OR=0.978, 95% CI: 0.968-0.999, p=0.040) had a boundary effect on prognosis. Conclusion: Patients with HPS secondary to autoimmune disease have better outcomes compared to patients complicated with Epstein-Barr virus infection or pulmonary involvement.

The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy.

With the continuous improvement of human technology, the medical field has gradually moved from molecular therapy to cellular therapy. As a safe and effective therapeutic tool, cell therapy has successfully created a research boom in the modern medical field. Mesenchymal stem cells (MSCs) are derived from early mesoderm and have high self-renewal and multidirectional differentiation ability, and have become one of the important cores of cell therapy research by virtue of their immunomodulatory and tissue repair capabilities. In recent years, the application of MSCs in various diseases has received widespread attention, but there are still various problems in the treatment of MSCs, among which the heterogeneity of MSCs may be one of the causes of the problem. In this paper, we review the correlation of MSCs heterogeneity to provide a basis for further reduction of MSCs heterogeneity and standardization of MSCs and hope to provide a reference for cell therapy.

Challenges and opportunities in animal models of psoriatic arthritis.

OBJECTIVE: To review the preparation, characteristics and research progress of different PsA animal models. METHODS: Computerized searches were conducted in CNKI, PubMed and other databases to classify and discuss the relevant studies on PsA animal models. The search keywords were "PsA and animal model(s), PsA and animal(s), PsA and mouse, PsA and mice, PsA and rat(s), PsA and rabbit(s), PsA and dog(s)" RESULTS: The experimental animals currently used to study PsA are mainly rodents, including mice and rats. According to the different methods of preparing the models, the retrieved animal models were classified into spontaneous or genetic mutation, transgenic and induced animal models. These PsA animal models involve multiple pathogenesis, some experimental animals' lesions appear in a short and comprehensive cycle, some have a high success rate in molding, and some are complex and less reproducibility. This article summarizes the preparation methods, advantages and disadvantages of different models. CONCLUSIONS: The animal models of PsA aim to mimic the clinicopathological alterations of PsA patients through gene mutation, transgenesis or targeted proinflammatory factor and to reveal new pathogenic pathways and therapeutic targets by exploring the pathological features and clinical manifestations of the disease. This work will have very far-reaching implications for the in-depth understanding of PsA and the development of new drugs.

Immunomodulatory effects of umbilical mesenchymal stem cell-derived exosomes on CD4+ T cells in patients with primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease that leads to the destruction of exocrine glands and multisystem lesions. Abnormal proliferation, apoptosis, and differentiation of CD4+ T cells are key factors in the pathogenesis of pSS. Autophagy is one of the important mechanisms to maintain immune homeostasis and function of CD4+ T cells. Human umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) may simulate the immunoregulation of MSCs while avoiding the risks of MSCs treatment. However, whether UCMSC-Exos can regulate the functions of CD4+ T cells in pSS, and whether the effects via the autophagy pathway remains unclear. METHODS: The study analyzed retrospectively the peripheral blood lymphocyte subsets in pSS patients, and explored the relationship between lymphocyte subsets and disease activity. Next, peripheral blood CD4+ T cells were sorted using immunomagnetic beads. The proliferation, apoptosis, differentiation, and inflammatory factors of CD4+ T cells were determined using flow cytometry. Autophagosomes of CD4+ T cells were detected using transmission electron microscopy, autophagy-related proteins and genes were detected using western blotting or RT-qPCR. RESULTS: The study demonstrated that the peripheral blood CD4+ T cells decreased in pSS patients, and negatively correlated with disease activity. UCMSC-Exos inhibited excessive proliferation and apoptosis of CD4+ T cells in pSS patients, blocked them in the G0/G1 phase, inhibited them from entering the S phase, reduced the Th17 cell ratio, elevated the Treg ratio, inhibited IFN-γ, TNF-α, IL-6, IL-17A, and IL-17F secretion, and promoted IL-10 and TGF-ß secretion. UCMSC-Exos reduced the elevated autophagy levels in the peripheral blood CD4+ T cells of patients with pSS. Furthermore, UCMSC-Exos regulated CD4+ T cell proliferation and early apoptosis, inhibited Th17 cell differentiation, promoted Treg cell differentiation, and restored the Th17/Treg balance in pSS patients through the autophagy pathway. CONCLUSIONS: The study indicated that UCMSC-Exos exerts an immunomodulatory effect on the CD4+ T cells, and maybe as a new treatment for pSS.

Exploiting the role of T cells in the pathogenesis of Sjögren's syndrome for therapeutic treatment.

Sjögrens syndrome (SS) is caused by autoantibodies that attack proprioceptive salivary and lacrimal gland tissues. Damage to the glands leads to dry mouth and eyes and affects multiple systems and organs. In severe cases, SS is life-threatening because it can lead to interstitial lung disease, renal insufficiency, and lymphoma. Histological examination of the labial minor salivary glands of patients with SS reveals focal lymphocyte aggregation of T and B cells. More studies have been conducted on the role of B cells in the pathogenesis of SS, whereas the role of T cells has only recently attracted the attention of researchers. This review focusses on the role of various populations of T cells in the pathogenesis of SS and the progress made in research to therapeutically targeting T cells for the treatment of patients with SS.

Role of the hedgehog signaling pathway in rheumatic diseases: An overview.

Hedgehog (Hh) signaling pathway is an evolutionarily conserved signal transduction pathway that plays an important regulatory role during embryonic development, cell proliferation, and differentiation of vertebrates, and it is often inhibited in adult tissues. Recent evidence has shown that Hh signaling also plays a key role in rheumatic diseases, as alterations in their number or function have been identified in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, systemic sclerosis, and Sjogren's Syndrome. As a result, emerging studies have focused on the blockade of this pathogenic axis as a promising therapeutic target in several autoimmune disorders; nevertheless, a greater understanding of its contribution still requires further investigation. This review aims to elucidate the most recent studies and literature data on the pathogenetic role of Hh signaling in rheumatic diseases.

Synovial Macrophages: Past Life, Current Situation, and Application in Inflammatory Arthritis.

Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane is an important as well as a highly specific component of the joint, and its lesions can lead to degeneration of the joint surface, causing pain and joint disability or affecting the patients' quality of life in severe cases. Synovial macrophages (SMs) are one of the cellular components of the synovial membrane, which not only retain the function of macrophages to engulf foreign bodies in the joint cavity, but also interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1ß, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis. SMs from different tissue sources have differently differentiated potentials and functional expressions. This article provides a summary on studies pertaining to SMs in inflammatory arthritis, and explores their role in its treatment, in order to highlight novel treatment modalities for the disease.

Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorate collagen-induced arthritis via immunomodulatory T lymphocytes.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease for which there are currently no effective therapies. Although mesenchymal stem cells (MSCs) can prevent arthritis through immunomodulatory mechanisms, there are several associated risks. Alternatively, MSC-derived small extracellular vesicles (sEVs) can mimic the effects of MSCs, while reducing the risk of adverse events. However, few studies have examined sEVs in the context of RA. Here, we evaluate the immunomodulatory effects of human umbilical cord MSC (hUCMSC)-derived sEVs on T lymphocytes in a collagen-induced arthritis (CIA) rat model to elucidate the possible mechanism of sEVs in RA treatment. We then compare these mechanisms to those of MSCs and methotrexate (MTX). METHODS: The arthritis index and synovial pathology were assessed. T lymphocyte proliferation and apoptosis, Th17 and Treg proportions, and interleukin (IL)-17, IL-10, and transforming growth factor (TGF)-ß expression were detected using flow cytometry. Retinoic acid receptor-related orphan receptor gamma t (RORγt) and forkhead box P3 (FOXP3), which are master transcriptional regulators of Th17 and Treg differentiation, were also assessed using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: sEV treatment ameliorated arthritis and inhibited synovial hyperplasia in a dose-dependent manner. These effects were mediated by inhibiting T lymphocyte proliferation and promoting their apoptosis, while decreasing Th17 cell proportion and increasing that of Treg cells in the spleen, resulting in decreased serum IL-17, and enhanced IL-10 and TGF-ß expression. Transcriptionally, sEVs decreased RORγt and increased FOXP3 expression in the spleen, and decreased RORγt and FOXP3 expression in the joints. In some aspects sEVs were more effective than MSCs and MTX in treating CIA. CONCLUSIONS: hUCMSC-derived sEVs ameliorate CIA via immunomodulatory T lymphocytes, and might serve as a new therapy for RA.

Pentraxin 3 is more accurate than C-reactive protein for Takayasu arteritis activity assessment: A systematic review and meta-analysis.

AIMS: Whether the circulating levels of pentraxin 3 (PTX3), an acute phase reactant (APR), are higher in active Takayasu arteritis (TAK), and if so, whether PTX3 is more accurate than C-reactive protein (CRP) in TAK activity assessment has been investigated in this study. STUDY DESIGN: Research works such as PubMed, Embase, ScienceDirect, Cochrane Library, and two Chinese literature databases (CNKI and WanFang) were searched for studies conducted till August 30th, 2019. Two investigators searched the studies independently, who evaluated the quality of the study using the Newcastle-Ottawa scale (NOS) and extracted data. Pooled standard mean difference (SMD) and diagnostic indexes, with a 95% confidence interval (CI), were calculated using a random-effect model. RESULTS: Totally, 8 studies involving 473 TAK (208 active and 265 inactive TAK) patients and 252 healthy controls were eventually included in the meta-analysis. PTX3 level in the blood in active TAK patients were found to be higher than that in dormant TAK with pooled SMD of 0.761 (95% CI = 0.38-1.14, p<0.0001; I2 = 68%, p of Q test = 0.003). And there was no publication bias. Among the 8 studies, 5 studies identified active TAK with both PTX3 and CRP. The pooled sensitivity, specificity, and AUC values of PTX3 in active TAK diagnosis were higher than those of CRP (0.78 [95% CI = 0.65-0.87] vs. 0.66 [95% CI = 0.53-0.77], p = 0.012; 0.85 [95% CI = 0.77-0.90] vs. 0.77 [95% CI = 0.56-0.90], p = 0.033; 0.88 [95% CI = 0.85-0.90] vs. 0.75 [95% CI = 0.71-0.79], p < 0.0001). It showed potential publication bias using Egger's test (p of PTX3 = 0.031 and p of CRP = 0.047). CONCLUSIONS: PTX3 might be better than CRP in the assessment of TAK activity. Yet, it should be cautious before clinical use for moderate heterogeneity and potential publication bias of the meta-analysis.