This study evaluated the significance of lymphocyte subset detection in peripheral blood in the diagnosis and prognosis of coronavirus disease 2019 (COVID-19). Our results revealed that CD3+ T cells, CD4+ T cells, CD8+ T cells, and natural killer cells were significantly decreased in patients with COVID-19. These patients had a relatively slight decrease in CD4+ T cells but a severe decrease in CD8+ T cells. The significantly elevated CD4/CD8 ratio was observed in COVID-19 patients. T-cell subset counts were related to the severity and prognosis of COVID-19, suggesting that the counts of CD8+ T and CD4+ T cells can be used as diagnostic markers of COVID-19 and predictors of disease severity.

Macrophages display remarkable plasticity, with the ability to undergo dynamic transition between classically and alternatively activated phenotypes. Long non-coding RNAs (lncRNAs) are more than 200 nucleotides in length and play roles in various biological pathways. However, the role of lncRNAs in regulating macrophage polarization has yet to be explored. In this study, lncRNAs expression profiles were determined in human monocyte-derived macrophages (MDMs) incubated in conditions causing activation toward M(IFN-γ + LPS) or M(IL-4) phenotypes. Compared with primary MDMs, 9343 lncRNAs and 5903 mRNAs were deregulated in M(IFN-γ + LPS) group (fold change ≥2.0, P < 0.05), 4592 lncRNAs and 3122 mRNAs were deregulated in M(IL-4) group. RT-qPCR results were generally consistent with the microarray data. Furthermore, we found that TCONS_00019715 is expressed at a higher level in M(IFN-γ + LPS) macrophages than in M(IL-4) macrophages. TCONS_00019715 expression was decreased when M(IFN-γ + LPS) converted to M(IL-4) whereas increased when M(IL-4) converted to M(IFN-γ + LPS). Knockdown of TCONS_00019715 following the activation of THP-1 cellls using IFN-γ and LPS diminished the expression of M(IFN-γ + LPS) markers, and elevated the expression of M(IL-4) markers. These data show a significantly altered lncRNA and mRNA expression profile in macrophages exposure to different activating conditions. Dysregulation of some of these lncRNAs may play important roles in regulating macrophage polarization.

Background/Aims: Dysregulated expression of circular RNAs (circRNAs) was demonstrated to be implicated in many diseases. Here, we aimed to determine circRNA profile in peripheral blood mononuclear cells (PBMCs) from active tuberculosis (TB) patients to identify novel biomarkers for TB. Methods: Expression profile of circRNAs in PBMCs from 3 active pulmonary TB patients and 3 healthy controls were analyzed by microarray assay. Six circRNAs were selected for validation using real time-quantitative PCR (qRT-PCR) in 40 TB patients and 40 control subjects. Receiver operating characteristic (ROC) curve was constructed to evaluate their values in TB diagnosis. Hsa_circRNA_001937 was chosen for further evaluation in an independent cohort consisting of 115 TB, 40 pneumonia, 40 COPD, 40 lung cancer patients and 90 control subjects. An eight-month follow up was performed in 20 newly diagnosed TB patients to investigate the expression change of hsa_circRNA_001937 after chemotherapy. Results: We revealed and confirmed that a number of circRNAs were dysregulated in TB patients. Of the six studied physio circRNAs, the levels of hsa_circRNA_001937, hsa_circRNA_009024 and hsa_ circRNA_005086 were significantly elevated and hsa_circRNA_102101, hsa_circRNA_104964 and hsa_circRNA_104296 were significantly reduced in PBMCs from TB patients as compared to healthy controls. ROC curve analysis suggested that hsa_circRNA_001937 has the largest area under the curve (AUC = 0.873, P<0.001). Hsa_circRNA_001937 was significantly increased in patients with TB compared with patients with pneumonia, COPD and lung cancer. Hsa_ circRNA_001937 was correlated with TB severity (r = 0.4053, P = 0.010) and its expression significantly decreased after treatment. Conclusion: This study identified a set of deregulated circRNAs in active TB PBMCs, our data also suggest that hsa_circRNA_001937 can be used as a potential diagnostic biomarker of TB.

ALKBH5 (alkylation repair homolog protein 5), FTO (fat mass and obesity-associated protein), and RNA N6-methyladenosine (m6A) demethylase, are essential for the m6A mRNA modification. YTHDF2 (YT521-B homology domains 2) called m6A “readers” can recognize m6A modification. As the key enzymes of m6A methylation modification, ALKBH5, FTO, and YTHDF2 have been implicated in many diseases. However, little is known about the role of ALKBH5, FTO, and YTHDF2 in rheumatoid arthritis (RA). We measured the mRNA expression of ALKBH5, FTO, and YTHDF2 in RA patients and controls by quantitative real-time polymerase chain reaction, and the global m6A content was detected by an ELISA-like format. The mRNA expression of ALKBH5, FTO, and YTHDF2 in RA patients was further analyzed to investigate its correlations with disease activity. And, multivariate analysis (logistic regression) was used to analyze the risk factors. The mRNA expression of ALKBH5, FTO, and YTHDF2 in RA patients was significantly decreased compared to controls. The mRNA expression of ALKBH5 was significantly increased in RA patients that received regular treatment. The mRNA expression of FTO was associated with disease activity score 28 (DAS28), complement 3 (C3), immunoglobulin G (IgG), and lymphocyte-to-monocyte ratio (LMR), some common markers for RA disease activity. The mRNA expression of YTHDF2 was associated with RBC, L%, N%, NLR, and LMR. Furthermore, logistic regression analysis revealed that decreased expression of ALKBH5, FTO, and YTHDF2 in peripheral blood was a risk factor for RA. Moreover, the peripheral blood global m6A content was significantly increased in patients with RA compared to CON, and increased m6A contents negatively correlated with decreased mRNA expression of FTO. In conclusion, this study firstly demonstrates the critical role of ALKBH5, FTO, and YTHDF2 in RA, which provides novel insights into recognizing the pathogenesis of RA and a promising biomarker for RA.

Background This study was aimed to explore the mRNA expression of m6A “writers” (METTL3, MTEEL14, and WTAP), “erasers” (FTO and ALKBH5), and “readers” (YTHDF2) in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients and investigate the relation between their expressions with clinical features. Methods In all, 54 SLE patients and 42 healthy controls (HC) were included in the current study. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) was used to investigate the mRNA expression of m6A “writers,” “erasers,” and “readers” in PBMCs from SLE patients and HC. Results Decreased mRNA expression of MTEEL14, ALKBH5, and YTHDF2 was observed in SLE patients compared with those in HC (p < .001). The decreased mRNA expression of METTL14 was associated with white blood cell count (WBC) and monocyte count (M), this decreased mRNA expression of ALKBH5 was associated with C‐reactive protein (CRP), neutrophil percentage (N%), lymphocyte percentage (L%), neutrophil–lymphocyte ratio (NLR), complement 3 (C3), and fever, and the decreased mRNA expression of YTHDF2 was associated with L%, NLR, C3, and fever. In addition, there was a positive correlation between mRNA expression of METTL14, ALKBH5, and YTHDF2 in PBMCs from SLE patients. Importantly, logistic regression analysis revealed that decreased mRNA expression of YTHDF2 was a risk factor for SLE. Conclusion Taken all together, our findings suggested decreased YTHDF2 that was associated with disease activity may play an important role in the pathogenesis of SLE, METTL14 and ALKBH5 may be concomitantly decreased.