Qualitative evaluation of connective tissue disease with cytomegalovirus infection: A meta-analysis of case reports.

BACKGROUND: The primary therapies for connective tissue disease include glucocorticoids and immunosuppressants. However, their prolonged usage can precipitate opportunistic infections, such as cytomegalovirus infection. When managing connective tissue disease complicated by cytomegalovirus infection, judicious selection of treatment modalities is crucial. This involves assessing the necessity for antiviral therapy and contemplating the reduction or cessation of glucocorticoids and immunosuppressants. OBJECTIVE: This investigation sought to methodically review existing literature regarding treating connective tissue disease patients with cytomegalovirus infection. METHODS: On July 5, 2023, an exhaustive literature search was conducted. Data analysis utilized the Kruskal-Wallis test or one-way analysis of variance, supplemented by Bonferroni post hoc testing. RESULTS: Our meta-analysis incorporated 88 studies encompassing 146 connective tissue disease patients with CMV infections. The results indicated that patients with connective tissue disease and cytomegalovirus disease benefitted more from antiviral therapy than those not receiving such treatment (P = 0.003, P < 0.005). Furthermore, the strategic reduction of glucocorticoids and/or immunosuppressants was beneficial (P = 0.037, P < 0.05). Poor clinical outcomes with glucocorticoid-immunosuppressant combination therapy compared to other treatment modalities. The findings also suggested that CMV infection patients fare better without Cyclosporine A than using it (P = 0.041, P < 0.05). CONCLUSION: Antiviral therapy is a viable treatment option in cases of connective tissue disease co-occurring with cytomegalovirus disease. Additionally, when connective tissue disease is stable, there is potential merit in reducing glucocorticoids and/or immunosuppressants, especially avoiding the combination of these drugs. For all cytomegalovirus infection patients, Cyclosporine A may be avoided wherever possible for selecting immunosuppressive agents if its use is not deemed essential in the treatment regimen.

Vitamin D levels in idiopathic inflammatory myopathy patients: a meta-analysis.

PURPOSE: This meta-analysis aimed to explore correlations between vitamin D and idiopathic inflammatory myopathy (IIM). METHODS: A comprehensive database search was conducted on 13 October 2020. Mean differences (MDs) and aggregated risk ratios (RR) with 95% confidence intervals (CIs) were used to determine the correlation between vitamin D deficiency (VDD) and IIM. Statistical analysis was performed with RevMan 5.4 and Stata15, statistical significance was set at p < 0.05. RESULTS: Search revealed five studies with 286 IIM patients and 480 healthy controls. Results with random-effects modeling indicated that serum vitamin D levels were significantly lower in IIM patients than in healthy controls (MD = -13.10 ng/mL; 95% CI: -16.51 to -9.68; p < 0.00001). No differences were found between patients with IIM and other autoimmune diseases on vitamin D levels (MD =-2.65 ng/mL; 95% CI: -11.31-6.01; p = 0.55). In two studies with 185 IIM patients, those with low vitamin D levels exhibited higher creatine kinase levels (MD = 85.20 IU/L; 95% CI: 72.67-97.73; p < 0.00001) than those with normal vitamin D levels. VDD was correlated with an increased risk of IIM (RR = 3.24, 95% CI: 1.81-5.79; p < 0.0001). CONCLUSION: This meta-analysis showed correlations between vitamin D level and IIM. The results indicated, VDD may be a risk factor for IIM, a determinant of immune dysregulation in IIM, or a consequence of IIM. Also, it implied further research to determine whether vitamin D supplementation is beneficial for patients with IIM.

Serum Uric Acid Concentrations and Risk of Adverse Outcomes in Patients With COVID-19.

Background: Although hyperuricemia frequently associates with respiratory diseases, patients with severe coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) can show marked hypouricemia. Previous studies on the association of serum uric acid with risk of adverse outcomes related to COVID-19 have produced contradictory results. The precise relationship between admission serum uric acid and adverse outcomes in hospitalized patients is unknown. Methods: Data of patients affected by laboratory-confirmed COVID-19 and admitted to Leishenshan Hospital were retrospectively analyzed. The primary outcome was composite and comprised events, such as intensive care unit (ICU) admission, mechanical ventilation, or mortality. Logistic regression analysis was performed to explore the association between serum concentrations of uric acid and the composite outcome, as well as each of its components. To determine the association between serum uric acid and in-hospital adverse outcomes, serum uric acid was also categorized by restricted cubic spline, and the 95% confidence interval (CI) was used to estimate odds ratios (OR). Results: The study cohort included 1854 patients (mean age, 58 years; 52% women). The overall mean ± SD of serum levels of uric acid was 308 ± 96 µmol/L. Among them, 95 patients were admitted to ICU, 75 patients received mechanical ventilation, and 38 died. In total, 114 patients reached composite end-points (have either ICU admission, mechanical ventilation or death) during hospitalization. Compared with a reference group with estimated baseline serum uric acid of 279-422 µmol/L, serum uric acid values ≥ 423 µmol/L were associated with an increased risk of composite outcome (OR, 2.60; 95% CI, 1.07- 6.29) and mechanical ventilation (OR, 3.01; 95% CI, 1.06- 8.51). Serum uric acid ≤ 278 µmol/L was associated with an increased risk of the composite outcome (OR, 2.07; 95% CI, 1.18- 3.65), ICU admission (OR, 2.18; 95% CI, 1.17- 4.05]), and mechanical ventilation (OR, 2.13; 95% CI, 1.06- 4.28), as assessed by multivariate analysis. Conclusions: This study shows that the association between admission serum uric acid and composite outcome of COVID-19 patients was U-shaped. In particular, we found that compared with baseline serum uric acid levels of 279-422 µmol/L, values ≥ 423 µmol/L were associated with an increased risk of composite outcome and mechanical ventilation, whereas levels ≤ 278 µmol/L associated with increased risk of composite outcome, ICU admission and mechanical ventilation.

Evaluation of biomarkers related to endothelial dysfunction: proof of vasculopathy in anti-melanoma differentiation-associated gene 5 dermatomyositis.

OBJECTIVES: We aimed to reveal evidence of endothelial dysfunction in the development of anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM). METHODS: Thirty anti-MDA5 DM patients were enrolled and compared with patients with polymyositis (PM) (n=10) and healthy controls (n=20). The concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1) and von Willebrand factor (vWF) as well as interferon-alpha (IFN-α) and Galcetin-9 in the peripheral blood were tested by enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma levels of sICAM-1, sVCAM-1, ET-1 and vWF were higher in the anti-MDA5 DM patients than in either the healthy controls or the PM patients. In the anti-MDA5 DM cohort, the ET-1 and vWF levels were significantly lower in the cases without cutaneous ulcers and ILD than the other cases. There was a strong positive relationship between the concentrations of ET-1 and Galectin-9 in the anti-MDA5 DM group. CONCLUSIONS: Our data suggest that endothelial dysfunction may be involved in the development of anti-MDA5 DM.

Increased Macroautophagy in Interferon-Gamma-Producing T Cells from Patients with Newly Diagnosed Systemic Lupus Erythematosus.

BACKGROUND: Imbalance of interferon-gamma (IFN-γ), interleukin (IL)-4, and IL-17 producing by T cells is confirmed to contribute to the pathogenesis of systemic lupus erythematosus (SLE). Autophagy is now emerging as a core player in the development and the function of the immune system. Therefore, we investigated the autophagic behavior in IFN-γ-, IL-4-, and IL-17-producing T cells from patients with SLE. METHODS: Thirty patients with SLE and 25 healthy controls matched for gender and age were recruited between September 2016 and May 2017. The autophagic levels in IFN-γ+ T cells, IL-4+ T cells, and IL-17+ T cells from patients with newly diagnosed SLE and healthy controls were measured using flow cytometry. The plasma levels of IFN-γ were determined by enzyme-linked immunosorbent assay in SLE patients and healthy controls. Unpaired t-tests and the nonparametric Mann-Whitney U-test were used to compare data from patients with SLE and controls. Spearman's rank correlation coefficient was applied for calculation of the correlation between parallel variables in single samples. RESULTS: Our results showed increased percentage of autophagy in IFN-γ+ T cells from patients with SLE and healthy controls ([8.07 ± 2.72]% vs. [3.76 ± 1.67]%, t = 5.184, P < 0.001), but not in IL-4+ T cells or IL-17+ T cells (P > 0.05) as compared to healthy donors. Moreover, the plasma levels of IFN-γ in SLE patients were significantly higher than those in healthy controls ([68.9 ± 29.1] pg/ml vs. [24.7 ± 17.6] pg/ml, t = 5.430, P < 0.001). Moreover, in SLE patients, the percentage of autophagy in IFN-γ+ T cells was positively correlated with the plasma levels of IFN-γ (r = 0.344, P = 0.046), as well as the disease activity of patients with SLE (r = 0.379, P = 0.039). CONCLUSION: The results indicate that autophagy in IFN-γ+ T cells from SLE patients is activated, which might contribute to the persistence of T cells producing IFN-γ, such as Th1 cells, and consequently result in the high plasma levels of IFN-γ, and then enhance the disease activity of SLE.

WITHDRAWN Monocyte chemoattractant protein-1 promoter-2518 G allele increases renal damage in systemic lupus erythematosus patients: result from a meta-analysis.

Ahead of Print article withdrawn by publisher. Not clarified suspected conflict of interest.

[The expression and significance of microtubule-associated protein 1 light chain 3-related protein-1 (LC3) mRNA in peripheral blood mononuclear cells in patients with systemic lupus erythematosus].

OBJECTIVE: Increasing evidence supports the involvement of autophagy in the etiopathology of autoimmune diseases. Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease characterized by production of multiple autoantibodies through poorly understood mechanism. In order to explore the role of autophagy in the development of SLE, the expression of autophagy related gene microtubule-associated protein 1 light chain 3 (MAPLC3) in peripheral blood mononuclear cells (PBMCs) was measured in patients with SLE. METHODS: The mRNA levels of LC3 in PBMCs from 56 SLE patients and 45 healthy individuals were detected by real-time quantitative polymerase chain reaction (qPCR) technique. Autophagy in PBMCs was also determined by flow cytometry (FACs) in 20 SLE patients and 15 healthy controls. The correlation between LC3 mRNA expression and disease activity of SLE (SLEDAI) was then analyzed. RESULTS: The mRNA level of LC3 (RQ) in SLE patients was obviously downregulated compared with that in healthy population (1.30 ± 0.10 vs 1.35 ± 0.09; P = 0.029), paralleled with the decreased autophagy rate detected by flow cytometry in PBMCs of SLE patients [(2.21 ± 1.07) % vs (9.91 ± 4.01) %;P = 0.047]. Moreover, LC3 mRNA expression level was negatively correlated with SLEDAI (r = -0.337, P = 0.023). However, when the clinical features of 27 SLE patients with decreased LC3 mRNA expression (RQ<1.351) were compared with those of other 29 SLE patients with normal or high LC3 mRNA expression (RQ>1.351), increasing rates of arthritis, serositis, hematological abnormalities were noted in patients with decreased LC3 mRNA expression yet without statistically significance. However, there was a significant difference between two groups in the incidence of renal involvement (P = 0.028). CONCLUSION: The impaired autophagy due to downregulated LC3 mRNA level in SLE patients indicates that autophagy plays a role in mediating the occurrence and development of SLE.

Salvia miltiorrhiza injection restores apoptosis of fibroblast-like synoviocytes cultured with serum from patients with rheumatoid arthritis.

Salvia miltiorrhiza injection (SMI) is a water­soluble agent, derived from Salvia miltiorrhiza (SM), that is traditionally used to treat cardiovascular and cerebrovascular diseases. Furthermore it has been demonstrated to possess the ability to induce apoptosis of tumor cells. However, it remains unclear whether SMI can induce apoptosis of rheumatoid arthritis (RA) fibroblast­like synoviocytes (FLS), which are hyperplastic in RA due to defective apoptosis. There is also evidence that allogenic serum may be associated with the induction of apoptosis. The aim of the present study was to investigate the involvement of serum during SMI­induced apoptosis in RA FLS. The results demonstrated that SMI could induce apoptosis of RA FLS, cultured with fetal bovine serum (FBS), in a dose­dependent manner. In addition, SMI decreased the expression of nuclear factor­κB in RA FLS nuclear extracts and inhibited the secretion of tumor necrosis factor­α. Fas ligand expression was not detected in RA FLS, in either the presence or absence of SMI. The pro­apoptotic genes B­cell lymphoma 2 (Bcl­2) associated X protein (Bax) and Fas, were shown to be upregulated following SMI stimulation, whereas the expression levels of the anti­apoptotic gene Bcl­2, were downregulated. Upon replacement of FBS with normal human serum, the apoptotic rate and Bax mRNA expression levels following SMI stimulation, were unchanged. However, culturing RA FLS with patient' serum (RPS), restored the apoptotic rate and Bax mRNA expression levels following SMI stimulation. There may be numerous mechanisms by which SMI inhibits RA FLS proliferation. The present study demonstrated that SMI can restore apoptosis of RA FLS cultured with RPS. These results indicate that SMI may have a potential role in the treatment of synovial hyperplasia of RA.

[The association of vitamin D receptor gene ApaI and BsmI polymorphism with systemic lupus erythematosus].

OBJECTIVE: To determine the distribution of vitamin D receptor (VDR) gene ApaI and BsmI polymorphism in systemic lupus erythematosus (SLE) and the association with SLE in Chinese Han patients. METHODS: Genomic DNA from 244 Chinese SLE patients and 162 sex and ethnically matched controls were typed for VDR ApaI and BsmI polymorphism combination by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Clinical characteristics were analyzed between different ApaI and BsmI genotypes. RESULTS: There was no significant difference between the distribution frequencies of allelic gene A and a in SLE patients and the controls, but the distribution frequency of genotypes heterozygote Aa in SLE patients was higher than that in the controls (38.9% vs 22.2%, χ(2) = 12.442, P = 0.000). There was no significant difference between the distribution frequency of allelic gene and genotypes of BsmI in SLE patients and the controls (P > 0.05). However, there was significant difference between the distribution frequencies of ApaI and BsmI genotypes combination in SLE patients and the controls (χ(2) = 18.226, P = 0.006). The distribution frequency of genotypes Aa-bb in SLE patients was higher than that in the controls (32.4% vs 17.9%, χ(2) = 10.449 P = 0.001), while the distribution frequency of genotypes Aa-bb in SLE patients was lower than that in the controls (30.3% vs 42.0%, χ(2) = 5.808, P = 0.016). Furthermore, analyzing the effect of VDR ApaI and BsmI polymorphism combination to the symptoms of SLE, significant difference was observed in SLE patients carrying Aa-bb genotypes involved in serositis (P = 0.003), hematological system disorder (P = 0.021), and anti-Sm antibodies (P = 0.01) compared with other genotypes. CONCLUSION: There is significant association between ApaI and BsmI gene polymorphism Aa-bb genotypes and the incidence of SLE in the Han population of China, and genotype Aa-bb is more involved in serositis, hematological system disorder and has a positive effect on production of antibodies.

[Relationship of vitamin D receptor gene Fok I polymorphism with systemic lupus erythematosus].

AIM: To investigate the relationship of vitamin D receptor (VDR) gene Fok I polymorphism with systemic lupus erythematosus (SLE) and to observe VDR mRNA levels in Chinese Han SLE patients. METHODS: Genomic DNAs from 271 Chinese SLE patients and 130 healthy controls were determined for Fok I polymorphism by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and VDR mRNA levels from 48 Chinese SLE patients and 38 healthy controls were detected by real-time polymerase chain reaction (RT-PCR). RESULTS: Gene frequencies of allelic F and f were significantly different between the SLE patients and the controls (P=0.001).The relative risk of SLE in the presence of allelic gene F was 1.630 (95%CI=1.210-2.196, P=0.001). The frequency of homozygote FF in the SLE patients was higher than that in the controls (42.8% vs 25.4%, x(2);=11.417, P=0.001). Serositis, anti-dsDNA antibody, anti-Sm antibody and anti-histone antibody in the SLE patients carrying homozygote FF and heterozygote Ff were higher than those in the SLE patients carrying homozygote ff (P=0.001, P=0.001, P=0.047, P=0.001, respectively). The VDR mRNA was decreased in the SLE patients, with a delta;Ct value of 9.26 ± 2.37 (P=0.026), as compared with a delta;Ct value of 7.82 ± 3.05 in the controls (the bigger of the delta;Ct value, the lower of VDR mRNA expression). The delta;Ct value of VDR mRNA in the SLE patients carrying FF and Ff was bigger than that in the SLE patients carrying ff (10.54 ± 1.88 vs 7.15 ± 3.78, P=0.019). CONCLUSION: VDR gene Fok I polymorphism is associated with SLE in the Han population of southern China. The SLE patients carrying F allel ± are more likely to have serositis and produce anti-dsDNA antibody, anti-Sm antibody and anti-Histone antibody, presumably as a result of down-regulation of VDR mRNA.

[Detecting anti-megakaryocyte antibodies in serum of systemic lupus erythematosus patients by indirect immunofluorescence].

This study was purposed to investigate the mechanism of thrombocytopenia in patients with systemic lupus erythematosus (SLE) through detecting anti-megakaryocyte antibodies in SLE patients. The serum anti-megakaryocyte antibodies in 36 SLE cases with thrombocytopenia were detected by using indirect immunofluorescence, the detected results were compared with detected results of 30 SLE cases without thrombocytopenia and 30 healthy persons. The results showed that the positive incidences of anti-megakaryocyte antibody in serum of 36 SLE cases with thrombocytopenia, 30 SLE cases without thrombocytopenia and 30 healthy persons were 19.4% (7/36), 6.7% (2/30) and 3.3% (1/30) respectively. As compared with SLE patients without thrombocytopenia and healthy persons, SLE patients with thrombocytopenia had higher incidence of anti-megakaryocyte antibodies, moreover there was significant difference between SLE patients with thrombocytopenia and healthy persons (p < 0.05), while there was no significant difference between SLE patients with or without thrombocytopenia (p > 0.05). It is concluded that autoantibodies against megakaryocytes exist in SLE patients and may partially contribute to the incidence of thrombocytopenia in SLE patients. The detection of anti-megakaryocyte antibodies with a enough case number is needed to make a final conclusion on thrombocytopenia pathogenesis in SLE.

Expression of FLICE-inhibitory protein in synovial tissue and its association with synovial inflammation in juvenile idiopathic arthritis.

OBJECTIVE: To examine the expression of FLICE-inhibitory protein (FLIP) in juvenile idiopathic arthritis (JIA) and analyze its correlation with synovial inflammation. METHODS: The expression of FLIP was assessed in 11 JIA and 3 normal synovial tissue samples by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The cell types expressing FLIP were further characterized, and the correlation of FLIP expression with the degree of synovial inflammation, as well as the activity of caspase 8 was then analyzed. RESULTS: RT-PCR revealed the expression of FLIP mRNA in all 11 JIA samples, but not in 3 normal synovial tissues. In JIA, FLIP expression could be found in both the lining and sublining layers, mainly in the macrophage-like cells. Moreover, the expression of FLIP in JIA synovial tissues was positively correlated with the degree of synovial inflammation (r = 0.563, P < 0.05). CONCLUSION: The expression of antiapoptotic FLIP in JIA synovial tissue and its correlation to accumulation of inflammatory cells in synovial tissue suggests that FLIP potentially extends the lifespan of synovial cells and thus contributes to the progression of joint destruction.