Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive autoantibody production and multi-organ involvement. Although the etiology of SLE still remains unclear, recent studies have characterized several pathogenic B cell subsets and regulatory B cell subsets involved in the pathogenesis of SLE. Among pathogenic B cell subsets, age-associated B cells (ABCs) are a newly identified subset of autoreactive B cells with T-bet-dependent transcriptional programs and unique functional features in SLE. Accumulation of T-bet⁺ CD11c⁺ ABCs has been observed in SLE patients and lupus mouse models. In addition, innate-like B cells with the autoreactive B cell receptor (BCR) expression and long-lived plasma cells with persistent autoantibody production contribute to the development of SLE. Moreover, several regulatory B cell subsets with immune suppressive functions have been identified, while the impaired inhibitory effects of regulatory B cells have been indicated in SLE. Thus, further elucidation on the functional features of B cell subsets will provide new insights in understanding lupus pathogenesis and lead to novel therapeutic interventions in the treatment of SLE.

Objective: T cells display significant phenotypical changes and play multiple roles in promoting the immune response in SLE. The frequencies of T cell subpopulations in SLE are still not well understood. To better understanding the phenotypic abnormalities of T cells in SLE will help us to clarify disease immunopathology and to find promising biomarkers for disease monitoring and control. Methods: Peripheral blood CD4⁺ and CD8⁺ T cells and their subsets were determined by flow cytometry. Forty-one active SLE patients were selected, including 28 new-onset patients and 13 relapsing patients. One hundred healthy controls (HCs) were enrolled as the control group. The percentages of these cell subsets between patients with SLE and HCs and their relationships with disease activity and autoantibody titers were analysed. Thirteen of 28 new-onset SLE patients were assessed before and after treatment. The changes in the frequencies of these cell subsets and their relationships with renal response were analysed. Results: There was a broad range of anomalies in the proportion of T cell subsets in patients with SLE compared with that of the HCs. Compared with the HCs, a higher frequency of memory T cells and a lower frequency of naïve T cells were noted in patients with SLE. In addition, an imbalance of CD28⁺ and CD28⁻ cells in CD4⁺ T cells was observed in patients with SLE. We found that the expanded CD4⁺CD28⁻ T cells did not decrease after treatment in patients who had impaired renal responses. It was very interesting to exhibit a negative correlation in the frequency between the CD4⁺CD28⁻ T cells and T regulatory (Treg) cells and a positive correlation between the frequency of CD4⁺CD28⁺ T cells and Treg cells in this study. Increased CD8⁺HLADR⁺ T cell and CD8⁺CD38⁺HLADR⁺ T cell counts were observed in patients with SLE, suggesting an impaired cytotoxic capacity of CD8⁺ T cells in SLE. Additionally, we found that CD8⁺CD38⁺HLADR⁺ T cells were closely associated with disease activity, autoantibody titres and renal prognosis. CD4⁺ CXCR5⁻PD1⁺ T cells were expanded in patients with SLE in this study and were associated with disease activity in SLE. Th1 (T helper type 1) cells and Treg cells were decreased, but frequencies of T follicular helper (Tfh) cells, Th2 cells, Th17 cells and Tfh17 cells were increased. A strong correlation between Th17 cells and Tregs with renal involvement was observed in this study. Conclusion: The proportions of CD4⁺CD28⁻ T cells, CD4⁺CXCR5⁻PD1⁺ T cells, CD8⁺HLADR⁺ T cells and CD8⁺CD38⁺HLADR⁺ T cells increased in patients with SLE and could be associated with disease activity and renal prognosis.

Objective. There is evidence that interleukin-6 (IL-6) upregulation plays a critical role in immunopathology of systemic lupus erythematosus (SLE). MicroRNA- (miRNA-) 98 was predicted to bind with the 3′-untranslated region (3′-UTR) of IL-6 gene. We hypothesized miR-98 through its regulation of IL-6 gene expression to influence cytokine production from peripheral blood mononuclear cells (PBMCs) in SLE. Methods. The expression of miR-98 and IL-6 mRNA in the PBMCs of 41 SLE patients and 20 healthy controls (HC) was detected by quantitative reverse transcription PCR (qRT-PCR). The correlations between miR-98 expression and clinical features were evaluated. Luciferase reporter assay was performed to identify miR-98 targets. miR-98 mimics, miR-98 inhibitor, and IL-6 overexpression vector were generated. Cell viability of PBMCs was assessed using MTT assay. Gene expression and protein level were determined by qRT-PCR and Western blotting. TNF-α, IL-8, IL-1β, and IL-10 levels in cultured supernatants were quantified using ELISA. Results. The expression of miR-98 was downregulated in PBMCs of SLE patients, and its expression is negatively associated with IL-6 levels. miR-98 expression was correlated with disease activity, lupus nephritis, and anti-dsDNA antibody. IL-6 mRNA was a target gene of miR-98. IL-6 overexpression promoted the proliferation of PBMCs and increased the levels of TNF-α, IL-8, IL-1β, and IL-10. Those effects were further enhanced by miR-98 inhibitor, while were suppressed by miR-98 mimics. miR-98 regulated the levels of STAT3 phosphorylation via its target gene IL-6. Conclusion. The current study revealed that miR-98 could ameliorate STAT3-mediated cell proliferation and inflammatory cytokine production via its target gene IL-6 in patients with SLE. These results suggest that miR-98 might serve as a potential target for SLE treatment and other IL-6-mediated diseases.

Objective: Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. Methods: Circulating γδ-T cells and their subsets (Vδ1⁺ T cells, Vδ2⁺ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. Results: Compared with that in HCs, the percentage of total γδ-T cells among CD3⁺ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1⁺ and Vδ2⁺ T cells among γδ-T cells was observed. The proportion of Vδ1⁺ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2⁺ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1⁺ T cells and Vδ2⁺ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2⁺ T cells. Moreover, Vδ2⁺ T cells, Vδ1⁺ T cells and Vδ1⁺PD-1⁺ T cells were associated with disease activity, and an increase in Vδ2⁺ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2⁺ T cells and their Vδ2⁺NKp30⁺ T-cell subpopulation might be associated with renal involvement in SLE. Conclusion: A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2⁺ T cells and their Vδ2⁺NKp30⁺ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.

To determine the comparative effectiveness of three evidence-informed approaches to delivering osteoarthritis (OA) care in real-world settings: face-to-face services, telehealth services or a mobile application (app). COASTAL (ACTRN12624000996561) comprises two aims: the primary aim is a three-arm, non-inferiority, comparative-effectiveness, type I hybrid implementation RCT; and the secondary aim is a superiority trial to compare the three interventions separately to an untreated, non-randomized control group. We will recruit 1348 participants (primary aim:1011 interventions; secondary aim:1011 interventions, 337 controls) with knee OA referred to a NSW public Osteoarthritis Chronic Care Program (OACCP). Eligible participants who consent to OACCP participation will be randomized 1:1:1 to receive care through the face-to-face OACCP, a telehealth service, or the "OA Coach" app, over 6-months. All participants will receive a standardized needs assessment; OA education; collaboratively developed, personalized management plan with a focus on therapeutic exercise, physical activity, pain management, and weight-management, according to each arm's mode of delivery. People who have declined OACCP participation will be eligible for the control group. The primary outcome is change in average knee pain during walking at 6-months (11-point NRS). Secondary, implementation, and economic evaluation outcomes will be collected at 6 and 12-months.The protocol was co-developed with people with knee OA, clinicians delivering the services, and other stakeholders. Ethical approval granted by the Northern Sydney Local Health District (2024/ETH01461). The results of this trial will provide critical evidence to help people with OA, clinicians, service planners and policymakers choose between different modes of delivering care for knee OA.

Objectives: Emerging evidence indicate that long noncoding RNAs (lncRNAs) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE) however, the contribution of lncRNAs to SLE remains largely unclear. Our study aimed to explore the lncRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from SLE patients. Methods: LncRNA sequencing was used to detect differentially expressed genes in PBMCs from 5 SLE-MIX samples and 3 healthy controls (HC)-MIX samples, and the expression of selected lncRNAs was further verified by real-time quantitative polymerase chain reaction (RT‒qPCR). The correlation of lncRNA expression with laboratory indicators as well the SLE disease activity index 2000 (SLEDAI‒2K) score from 72 SLE patients was assessed by Spearman’s test. The association between lncRNA ENST00000597482 and organ involvement in SLE patients was determined by the Mann‒Whitney U test. Moreover, lymphocyte subsets in peripheral blood from SLE patients were measured by flow cytometry. In addition, the diagnostic value of lncRNAs in predicting SLE was evaluated by receiver operating characteristic (ROC) curve analysis. Results: The lncRNA expression profiles demonstrated 218 differentially expressed lncRNAs, including 121 upregulated genes and 97 downregulated genes, in PBMCs from SLE patients compared to HCs. Among the 10 candidate genes selected, only lncRNA ENST00000597482, which was lower in SLE PBMCs than in HCs, was consistent with the sequencing results. LncRNA ENST00000597482 expression was negatively correlated with SLEDAI-2K score and the titres of ANA antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies. Of note, SLE patients with lower expression of lncRNA ENST00000597482 were prone to develop organ involvement. Furthermore, lncRNA ENST00000597482 exhibited potential diagnostic value in differentiating SLE patients from HCs. Conclusions: LncRNA ENST00000597482 expression was lower in PBMCs from SLE patients than HCs and was negatively correlated with the SLEDAI-2K score and autoantibody titres. In addition, lncRNA ENST00000597482 could act as a novel biomarker for disease activity and diagnosis of SLE.