CD5L up-regulates the TGF-ß signaling pathway and promotes renal fibrosis.

Renal fibrosis is the common final pathway of progressive renal diseases, in which the macrophages play an important role. ELISA was used to detect CD5 antigen-like (CD5L) in serum samples from end-stage renal disease (ESRD), as well as in mice serum with unilateral ureteral occlusion (UUO). Recombinant CD5L was injected into UUO mice to assess renal injury, fibrosis, and macrophage infiltration. The expression of CD5L was significantly upregulated in the serum of patients with ESRD and UUO mice. Histological analysis showed that rCD5L-treated UUO mice had more severe renal injury and fibrosis. Furthermore, rCD5L promoted the phenotypic transfer of monocytes from Ly6Chigh to LyC6low. RCD5L promoted TGF-ß signaling pathway activation by promoting Smad2/3 phosphorylation. We used Co-IP to identify HSPA5 interact with CD5L on cell membrane could inhibit the formation of the Cripto/HSPA5 complex, and promote the activation of the TGF-ß signaling pathway. The CD5L antibody could reduce the degree of renal fibrosis in UUO mice.

CD5L is upregulated upon infection with Mycobacterium tuberculosis with no effect on disease progression.

Tuberculosis (TB) alone caused over a billion deaths in the last 200 years, making it one of the deadliest diseases to humankind. Understanding the immune mechanisms underlying protection or pathology in TB is key to uncover the much needed innovative approaches to tackle TB. The scavenger receptor cysteine-rich molecule CD5 antigen-like (CD5L) has been associated with TB, but whether and how CD5L shapes the immune response during the course of disease remains poorly understood. Here, we show an upregulation of CD5L in circulation and at the site of infection in C57BL/6 Mycobacterium tuberculosis-infected mice. To investigate the role of CD5L in TB, we studied the progression of M. tuberculosis aerosol infection in a recently described genetically engineered mouse model lacking CD5L. Despite the increase of CD5L during infection of wild-type mice, absence of CD5L did not impact bacterial burden, histopathology or survival of infected mice. Absence of CD5L associated with a modest increase in the numbers of CD4+ T cells and the expression of IFN-γ in the lungs of infected mice, with no major effect in overall immune cell dynamics. Collectively, this study confirms CD5L as a potential diagnostic biomarker to TB, showing no discernible impact on the outcome of the infection.

CD5L induces inflammation and survival in RA-FLS through ERK1/2 MAPK pathway.

OBJECTIVE: To explore the effect of CD5-like molecule (CD5L) on rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS) and the relative molecular mechanism of CD5L in it. METHODS: Recombinant protein CD5L was used to stimulate the cultured RA-FLS cells. The inflammation-related cytokines were determined by real time-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The signal molecules and apoptosis-related molecules were detected by western blot assay (WB), and cell counting kit-8 (CCK-8) was used to detect the proliferation. RESULTS: CD5L can increase the production of IL-6, IL-8, and TNF-α and this effect can be inhibited by signal pathway inhibitor. At the same time, CD5L activated ERK1/2 MAPK signal, inhibitor treatment can weaken the intensity of phosphorylation. In addition, CD5L can enhance the proliferation ability of RA-FLS. CONCLUSION: CD5L induces the production of inflammatory cytokines in RA-FLS through the ERK1/2 MAPK pathway and increases cell survival.

Fibroblastic reticular cell-derived exosomes are a promising therapeutic approach for septic acute kidney injury.

Sepsis-induced acute kidney injury (S-AKI) is highly lethal, and effective drugs for treatment are scarce. Previously, we reported the robust therapeutic efficacy of fibroblastic reticular cells (FRCs) in sepsis. Here, we demonstrate the ability of FRC-derived exosomes (FRC-Exos) to improve C57BL/6 mouse kidney function following cecal ligation and puncture-induced sepsis. In vivo imaging confirmed that FRC-Exos homed to injured kidneys. RNA-Seq analysis of FRC-Exo-treated primary kidney tubular cells (PKTCs) revealed that FRC-Exos influenced PKTC fate in the presence of lipopolysaccharide (LPS). FRC-Exos promoted kinase PINK1-dependent mitophagy and inhibited NLRP3 inflammasome activation in LPS-stimulated PKTCs. To dissect the mechanism underlying the protective role of Exos in S-AKI, we examined the proteins within Exos by mass spectrometry and found that CD5L was the most upregulated protein in FRC-Exos compared to macrophage-derived Exos. Recombinant CD5L treatment in vitro attenuated kidney cell swelling and surface bubble formation after LPS stimulation. FRCs were infected with a CD5L lentivirus to increase CD5L levels in FRC-Exos, which were then modified in vitro with the kidney tubular cell targeting peptide LTH, a peptide that binds to the biomarker protein kidney injury molecule-1 expressed on injured tubule cells, to enhance binding specificity. Compared with an equivalent dose of recombinant CD5L, the modified CD5L-enriched FRC-Exos selectively bound PKTCs, promoted kinase PINK-ubiquitin ligase Parkin-mediated mitophagy, inhibiting pyroptosis and improved kidney function by hindering NLRP3 inflammasome activation, thereby improving the sepsis survival rate. Thus, strategies to modify FRC-Exos could be a new avenue in developing therapeutics against kidney injury.

CD5L is a canonical component of circulatory IgM.

Immunoglobulin M (IgM) is an evolutionary conserved key component of humoral immunity, and the first antibody isotype to emerge during an immune response. IgM is a large (1 MDa), multimeric protein, for which both hexameric and pentameric structures have been described, the latter additionally containing a joining (J) chain. Using a combination of single-particle mass spectrometry and mass photometry, proteomics, and immunochemical assays, we here demonstrate that circulatory (serum) IgM exclusively exists as a complex of J-chain-containing pentamers covalently bound to the small (36 kDa) protein CD5 antigen-like (CD5L, also called apoptosis inhibitor of macrophage). In sharp contrast, secretory IgM in saliva and milk is principally devoid of CD5L. Unlike IgM itself, CD5L is not produced by B cells, implying that it associates with IgM in the extracellular space. We demonstrate that CD5L integration has functional implications, i.e., it diminishes IgM binding to two of its receptors, the FcαµR and the polymeric Immunoglobulin receptor. On the other hand, binding to FcµR as well as complement activation via C1q seem unaffected by CD5L integration. Taken together, we redefine the composition of circulatory IgM as a J-chain containing pentamer, always in complex with CD5L.

CD5L Deficiency Protects Mice Against Bleomycin-Induced Pulmonary Fibrosis.

BACKGROUND: Pulmonary fibrosis (PF), the most common clinical type of irreversible interstitial lung disease with one of the worse prognoses, has a largely unknown molecular mechanisms that underlies its progression. CD5 molecule-like (CD5L) functions in an indispensable role during inflammatory responses; however, whether CD5L functions in regulating bleomycin (BLM)-induced lung fibrosis is less clear. METHODS: Herein, we describe the engineering of Cd5l knockout mice using CRISPR/Cas9 gene editing technology. The BLM-induced model of acute lung injury represents the most widely used experimental rodent model for PF. RESULTS: Taking advantage of this model, we demonstrated that both CD5L mRNA and protein were enriched in the lungs of mice following BLM-induced pulmonary fibrosis. Inhibition of CD5L prevented mice from BLM-induced lung fibrosis and injury. In particular, a lack of CD5L significantly attenuated inflammatory response and promoted M2 polarization in the lung of this pulmonary fibrosis model as well as suppressing macrophage apoptosis. CONCLUSIONS: Collectively, our data support that CD5L deficiency can suppress the development of pulmonary fibrosis, and also provides new molecular targets for the use of immunotherapy to treat lung fibrosis.

CD5L aggravates rheumatoid arthritis progression via promoting synovial fibroblasts proliferation and activity.

Rheumatoid arthritis (RA) is a chronic inflammatory disease with progressive cartilage erosion and joint destruction. Synovial fibroblasts (SFs) play a crucial role in the pathogenesis of RA. This study aims to explore the function and mechanism of CD5L during RA progression. We examined the levels of CD5L in synovial tissues and SFs. The collagen-induced arthritis (CIA) rat models were used to investigate the effect of CD5L on RA progression. We also investigated the effects of exogenous CD5L on the behavior and activity of RA synovial fibroblasts (RASFs). Our results showed that CD5L expression was significantly upregulated in synovium of RA patients and CIA-rats. Histology and Micro-CT analysis showed that synovial inflammation and bone destruction were more severe in CD5L-treated CIA rats compared with control rats. Correspondingly, CD5L blockade alleviated bone damage and synovial inflammation in CIA-rats. The exogenous CD5L treatment promoted RASFs proliferation invasion and proinflammatory cytokine production. Knockdown of CD5L receptor by siRNA significantly reversed the effect of CD5L treatment on RASFs. Moreover, we observed that CD5L treatment potentiated PI3K/Akt signaling in the RASFs. The promoted effects of CD5L on IL-6 and IL-8 expression were significantly reversed by PI3K/Akt signaling inhibitor. In conclusion, CD5L promote RA disease progression via activating RASFs. CD5L blocking is a potential therapeutic approach for RA patients.

[CD5L is elevated in the serum of patients with candidemia and promotes disease progression in mouse models].

OBJECTIVE: To investigate the changes of CD5L levels in patients with candidemia and explore the role of CD5L in progression of candidemia. METHODS: Twenty healthy control individuals, 27 patients with bacteremia and 35 patients with candidemia were examined for serum CD5L levels using ELISA, and the correlations of CD5L level with other serological indicators were analyzed. A C57BL/6 mouse model of candidemia induced by intravenous injection of Candida albicans were treated with intraperitoneal injection of recombinant CD5L protein, and renal histopathological and serological changes were analyzed to assess renal injures. The effects of CD5L treatment on general condition, fungal burden, of survival of the mice were observed, and the changes in serum IL-6 and IL-8 levels of the mice were detected using ELISA. RESULTS: CD5L levels were significantly elevated in patients with candidemia and positively correlated with WBC, BDG, Scr and PCT levels. The mouse model of candidemia also showed significantly increased serum and renal CD5L levels, and CD5L treatment significantly increased fungal burden in the renal tissue, elevated IL-6 and IL-8 levels in the serum and kidney, aggravated renal tissue damage, and reduced survival rate of candidemia mice. CONCLUSION: Serum CD5L levels are increased in patients with candidemia, and treatment with CD5L aggravates candidemia in mouse models.

Serum level of apoptosis inhibitor of macrophage in dogs with histiocytic sarcoma and its association with the disease.

Histiocytic sarcoma (HS) is a rare neoplasm of macrophages or dendritic cells with a poor prognosis in dogs. As the apoptosis inhibitor of macrophage (AIM) is characteristically expressed in canine macrophages, we hypothesised that AIM is involved in the development or progression of HS in dogs. In this study, AIM expression in the tumour region and serum AIM levels in dogs with HS was assessed. Additionally, the effects of AIM overexpression on HS cell viability were investigated using a HS cell line that was selected from five validated HS cell lines. Immunohistochemistry showed that AIM expression was observed in the cytoplasm of the HS cells. CD36, a candidate AIM receptor, was also observed on the cell membrane of HS cells. When the serum AIM level was detected in 36 dogs with HS and 10 healthy dogs via western blot analysis, the AIM levels in the HS dogs were significantly higher than those in the controls. AIM mRNA expression in the 5 HS cell lines varied but was higher than that in the other tumour-derived lines. Among the five HS cell lines, DH82 originally had lower AIM and the highest CD36 expression. When AIM was overexpressed in DH82, therein cell growth speed and invasion, apoptosis inhibition and phagocytic activity were strongly upregulated. These data suggest that elevated intra-tumour expression of AIM could induce the progression of HS cells in dogs. Moreover, elevated serum AIM levels in dogs with HS could serve as a biomarker of HS.

Macrophage CD5L is a target for cancer immunotherapy.

BACKGROUND: Reprogramming of immunosuppressive tumor-associated macrophages (TAMs) presents an attractive therapeutic strategy in cancer. The aim of this study was to explore the role of macrophage CD5L protein in TAM activity and assess its potential as a therapeutic target. METHODS: Monoclonal antibodies (mAbs) against recombinant CD5L were raised by subcutaneous immunization of BALB/c mice. Peripheral blood monocytes were isolated from healthy donors and stimulated with IFN/LPS, IL4, IL10, and conditioned medium (CM) from different cancer cell lines in the presence of anti-CD5L mAb or controls. Subsequently, phenotypic markers, including CD5L, were quantified by flow cytometry, IF and RT-qPCR. Macrophage CD5L protein expression was studied in 55 human papillary lung adenocarcinoma (PAC) samples by IHC and IF. Anti-CD5L mAb and isotype control were administered intraperitoneally into a syngeneic Lewis Lung Carcinoma mouse model and tumor growth was measured. Tumor microenvironment (TME) changes were determined by flow cytometry, IHC, IF, Luminex, RNAseq and RT-qPCR. FINDINGS: Cancer cell lines CM induced an immunosuppressive phenotype (increase in CD163, CD206, MERTK, VEGF and CD5L) in cultured macrophages. Accordingly, high TAM expression of CD5L in PAC was associated with poor patient outcome (Log-rank (Mantel-Cox) test p = 0.02). We raised a new anti-CD5L mAb that blocked the immunosuppressive phenotype of macrophages in vitro. Its administration in vivo inhibited tumor progression of lung cancer by altering the intratumoral myeloid cell population profile and CD4+ T-cell exhaustion phenotype, thereby significantly modifying the TME and increasing the inflammatory milieu. INTERPRETATION: CD5L protein plays a key function in modulating the activity of macrophages and their interactions within the TME, which supports its role as a therapeutic target in cancer immunotherapy. FUNDING: For a full list of funding bodies, please see the Acknowledgements.

Human coagulation factor X and CD5 antigen-like are potential new members of the zonulin family proteins.

Zonulin is a physiologic epithelial and endothelial permeability modulator. Zonulin increases antigen trafficking from the gut lumen into the bloodstream and in between body compartments, a mechanism linked to many chronic inflammatory diseases. Upon its initial discovery, it was noted that zonulin was not a single protein, but rather a family of structurally and functionally related proteins referred to as the zonulin family proteins (ZFPs). ZFPs are members of the mannose associated serine proteases (MASP) family and are the result of high mutation rates leading to many zonulin polymorphisms. Pre-haptoglobin 2, the precursor of haptoglobin 2, was identified as the first eukaryotic member of the ZFPs, and properdin, a key positive regulator of the alternative pathway, as a second member. In this study, we report two additional proteins that are likely ZFPs. Human coagulation factor X (FX) and CD5 antigen-like (CD5L). Both FX and CD5L recombinant proteins were detected by anti-zonulin antibody in Western immunoblot analysis, and both proteins decreased epithelial barrier competency of Caco-2 cell monolayers as established by the Trans Epithelial Electrical Resistance (TEER) assay. These results indicate that FX and CD5L have structural and functional similarities with previously identified ZFPs and, therefore, can be considered new members of this family of proteins.

The Presence of Psoriasis, Metabolic Syndrome and Their Combination Increases the Serum Levels of CRP and CD5L but Not sCD200R1 and sTLR2 in Participants.

Psoriasis and metabolic syndrome (MetS) are chronic inflammatory conditions associated with the dysregulation of immune system reactivity. The inflammatory processes of both diseases have not yet been fully characterized, and the evaluation of proteins/markers that could be involved in their pathogenesis is of great importance. We selected four markers: CRP, sCD200R1, CD5L, and sTLR2; in particular, sCDR2001 has not yet been measured in the context of psoriasis and metabolic syndrome. Material and methods: In the study, 64 controls and 43 patients with psoriasis with or without a metabolic syndrome were enrolled. The levels of selected markers were measured using ELISA kits. Results: CRP levels were significantly higher in psoriasis patients, especially in the subgroup of patients with MetS compared to nonMetS patients (p < 0.01). sCD200R1 and sTLR2 were not significantly different between groups and subgroups; however, CD200R1 levels were slightly higher in both control groups compared to both groups of patients. CD5L levels were significantly higher in patients with MetS compared to nonMets patients (p < 0.02). We also evaluated the correlations between parameters in controls and patients' groups, as well as in subgroups. Correlations between BMI and CRP were found in all groups and subgroups. Other correlations were group- and subgroup-specific. For example, in the patients' group, CD5L correlated with sCD200R1 (p < 0.05) and in MetS controls, with age (p < 0.03). Conclusion: The results show that the presence of systemic inflammation associated with psoriasis and metabolic syndrome and their combination alters the expression of specific molecules, especially CRP and CD5L, which were significantly increased in patients with psoriasis and a metabolic syndrome compared to controls without metabolic syndromes. Correlations between CRP and BMI in all groups suggest that overweight and obesity increase the intensity of inflammation and potentiate CD5L expression. In contrast, levels of molecules that may limit inflammation were not increased in psoriasis and metabolic syndrome subjects (they were non-significantly lower compared with healthy controls), which may reflect the chronic nature of both diseases and the exhaustion of inhibitory mechanisms.

CD5L-associated gene analyses highlight the dysregulations, prognostic effects, immune associations, and drug-sensitivity predicative potentials of LCAT and CDC20 in hepatocellular carcinoma.

BACKGROUND: The dysregulation of CD5L has been reported in hepatocellular carcinoma (HCC). However, its functions in HCC were controversial. In this study, we aimed to identify CD5L-associated pathways and markers and explore their values in HCC diagnosis, prognosis and treatment. METHODS: HCC datasets with gene expression profiles and clinical data in TCGA and ICGC were downloaded. The immune/stroma cell infiltrations were estimated with xCell. CD5L-associated pathways and CD5L-associated genes (CD5L-AGs) were identified with gene expression comparisons and gene set enrichment analysis (GSEA). Cox regression, Kaplan-Meier survival analysis, and least absolute shrinkage and selection operator (LASSO) regression analysis were performed. The correlations of the key genes with immune/stroma infiltrations, immunoregulators, and anti-cancer drug sensitivities in HCC were investigated. At protein level, the key genes dysregulations, their correlations and prognostic values were validated in clinical proteomic tumor analysis consortium (CPTAC) database. Serum CD5L and LCAT activity in 50 HCC and 30 normal samples were evaluated and compared. The correlations of serum LCAT activity with alpha-fetoprotein (AFP), albumin (ALB) and high-density lipoprotein (HDL) in HCC were also investigated. RESULTS: Through systemic analyses, 14 CD5L-associated biological pathways, 256 CD5L-AGs and 28 CD5L-associated prognostic and diagnostic genes (CD5L-APDGs) were identified. A risk model consisting of LCAT and CDC20 was constructed for HCC overall survival (OS), which could discriminate HCC OS status effectively in both the training and the validation sets. CD5L, LCAT and CDC20 were shown to be significantly correlated with immune/stroma cell infiltrations, immunoregulators and 31 anti-cancer drug sensitivities in HCC. At protein level, the dysregulations of CD5L, LCAT and CDC20 were confirmed. LCAT and CDC20 were shown to be significantly correlated with proliferation marker MKI67. In serum, no significance of CD5L was shown. However, the lower activity of LCAT in HCC serum was obvious, as well as its significant positive correlations ALB and HDL concentrations. CONCLUSIONS: CD5L, LCAT and CDC20 were dysregulated in HCC both at mRNA and protein levels. The LCAT-CDC20 signature might be new predicator for HCC OS. The associations of the three genes with HCC microenvironment and anti-cancer drug sensitivities would provide new clues for HCC immunotherapy and chemotherapy.

Antibody therapeutics for epithelial ovarian cancer.

INTRODUCTION: High-grade serous ovarian carcinoma (HGSC) is an aggressive subtype of epithelial ovarian carcinoma (EOC) and remains the most lethal gynecologic cancer. A lack of effective and tolerable therapeutic options and nonspecific symptoms at presentation with advanced stage of disease are among the challenges in the management of the disease. AREAS COVERED: An overview of ovarian cancer, followed by a discussion of the current therapeutic regimes and challenges that arise during and after the treatment of EOC. We discuss different formats of antibody therapeutics and their usage in targeting validated targets implicated in ovarian cancer, as well as three emerging novel proteins as examples recently implicated in their contribution to adaptive resistance in ovarian cancer. EXPERT OPINION: Antibody therapeutics allow for a unique and effective way to target proteins implicated in cancer and other diseases, and have the potential to radically change the outcomes of patients suffering from ovarian cancer. The vast array of targets that have been implicated in ovarian cancer and yet the lack of effective therapeutic options for patients further stresses the importance of discovering novel proteins that can be targeted, as well as predictive biomarkers that can inform the stratification of patients into treatment-specific populations.

CD5L attenuates allergic airway inflammation by expanding CD11chigh alveolar macrophages and inhibiting NLRP3 inflammasome activation via HDAC2.

Allergic asthma is an airway inflammatory disease dominated by type 2 immune responses and there is currently no curative therapy for asthma. CD5-like antigen (CD5L) has been known to be involved in a variety of inflammatory diseases. However, the role of CD5L in allergic asthma remains unclear. In the present study, mice were treated with recombinant CD5L (rCD5L) during house dust mite (HDM) and ovalbumin (OVA) challenge to determine the role of CD5L in allergic asthma, and the underlying mechanism was further explored. Compared with PBS group, serum CD5L levels of asthmatic mice were significantly decreased, and the levels of CD5L in lung tissues and bronchoalveolar lavage fluid (BALF) were significantly increased. CD5L reduced airway inflammation and Th2 immune responses in asthmatic mice. CD5L exerted its anti-inflammatory function by increasing CD11chigh alveolar macrophages (CD11chigh AMs), and the anti-inflammatory role of CD11chigh AMs in allergic asthma was confirmed by CD11chigh AMs depletion and transfer assays. In addition, CD5L increased the CD5L+ macrophages and inhibited NLRP3 inflammasome activation by increasing HDAC2 expression in lung tissues of asthmatic mice. Hence, our study implicates that CD5L has potential usefulness for asthma treatment.

CD5L Secreted by Macrophage on Atherosclerosis Progression Based on Lipid Metabolism Induced Inflammatory Damage.

To explore the molecular mechanism of exosomal protein CD5L secreted by macrophage to promote the progression of atherosclerosis. Twenty cases of patients with atherosclerosis (AS) and 20 cases of healthy subjects were collected. Morphological properties of exosomes were identified by transmission electron microscopy, and the marker proteins CD63 and CD81 of exosomes were measured by Western blot. The secretion of inflammatory factors in the blood supernatant were analyzed by ELISA. Atherosclerosis cell models were established by transwell and separated into three groups: first group was treated with exosome inhibitor (GW4869), second group was injected with CD5L protein and third group was model control. Morphological properties of exosomes were identified by transmission electron microscopy, and the marker proteins CD63 and CD81 of exosomes were measured by Western blot. The levels of TNF-α, IL-1ß, IL-6, IL-13, IL-17A, IL-31 in the cells were analyzed by ELISA. Analysis of the expression and distribution of IL-17RA in vascular smooth muscle cells by immunofluorescence. The proteins of CD63, CD81, CD5L were high expressed in AS group compared to healthy subject group. Cell test results showed that protein levels of CD63, CD81, CD5L in AS group were much higher than that in normal group. Immunofluorescence showed that the expression level of IL-17RA in cell membrane was the highest in the AS model group, and the expression of IL-17RA was decreased in GW4869 group and CD5L group. Expression of inflammatory factors in AS was much higher than that in GW4869 group and CD5L group. The exosomal protein CD5L secreted by macrophage promotes the development of atherosclerosis based on lipid metabolism-induced inflammatory damage of vascular smooth muscle cells.

Role of CD5L and SRD5A2 as Prognostic Biomarkers for Hepatocellular Carcinoma.

PURPOSE: Due to the limitations of currently available biomarkers, new biomarkers are needed to accurately predict the prognosis of patients with hepatocellular carcinoma (HCC) patients. METHODS: In this study, we screened for differentially expressed genes (DEGs) in the tumor and the adjacent tissues using the four gene expression array (GSE14520, GSE45267, GSE121248, GSE62232) of the Gene Express Omnibus (GEO) database. RESULTS: Subsequently, 47 overlapping DEGs were identified in four GEO datasets, which were mostly located on chromosomes 5q and 6q, distributed in the liver and CD105-positive endothelial cells, and closely related to HCC. Function enrichment revealed 47 DEGs were related to HCC, and involved in steroid /lipid /retinol metabolism, bile secretion and p53 signalling pathway. The Kaplan-Meier plotter analysis (http://www.kmplot.com/) identified 26 and 40 genes associated with the 5-year overall survival (OS) and relapse-free survival (RFS). We found that CD5L and SRD5A2 were independent prognostic factors for 5-year OS (P=0.036) and RFS (P=0.044) in HCC patients from GSE14520, respectively. Clinicopathological features including BCLC stage, cirrhosis, and risk signature for predicted metastasis were used to construct and validate a nomogram for 5-year OS with C-index of 0.732 and 0.717 in the training and validation cohort, respectively. SRD5A2, BCLC stage and gender was independent prognostic factors for RFS which were used to build a nomogram with the C-index of 0.666 and 0.682 in the training and validation cohort, respectively. CONCLUSION: CD5L can facilitate individualized, targeted therapy for HCC patients.

Increase in CD5L expression in the synovial membrane of knee osteoarthritis patients with obesity.

INTRODUCTION: Obesity appears to be a powerful risk factor for the development of knee osteoarthritis (KOA), but the mechanisms of this are not fully understood. CD5L is expressed in tissue macrophages and is increased in obese mice. We hypothesized that CD5L expression is increased in the synovial membrane (SM) of obese KOA patients. Here, we investigated CD5L expression in the SM of these patients. MATERIAL AND METHODS: Ninety KOA patients (26 males, 64 females) were allocated to one of three groups based on body mass index (BMI): normal weight (NW, < 25 kg/m2), overweight (OW, 25-29.99 kg/m2) and obese (OB, ≥ 30 kg/m2), according to the World Health Organization BMI classification (each n = 30). Expression of CD5L in SM among the groups was compared using real-time polymerase chain reaction. To investigate CD5L-expressing cells in SM, CD14+ (macrophage fraction) and CD14- (fibroblast fraction) cells were separated from the SM. RESULTS: CD5L expression was significantly higher in the OB group than in the NW and OW groups (p < 0.001). CD5L expression was observed in the CD14+ fraction but not in the CD14- fraction. CONCLUSIONS: CD5L is highly expressed in the SM of KOA patients with obesity. Further investigation is required to identify the role of CD5L in the relationship between KOA pathology and obesity.

Circulating CD5L is associated with cardiovascular events and all-cause mortality in individuals with chronic kidney disease.

This study assessed the association of CD5L and soluble CD36 (sCD36) with the risk of a cardiovascular event (CVE), including CV death and all-cause mortality in CKD. We evaluated the association of CD5L and sCD36 with a predefined composite CV endpoint (unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular accident, congestive heart failure, arrhythmia, peripheral arterial disease [PAD] or amputation by PAD, aortic aneurysm, or death from CV causes) and all-cause mortality using Cox proportional hazards regression, adjusted for CV risk factors. The analysis included 1,516 participants free from pre-existing CV disease followed up for 4 years. The median age was 62 years, 38.8% were female, and 26.8% had diabetes. There were 98 (6.5%) CVEs and 72 (4.8%) deaths, of which 26 (36.1%) were of CV origin. Higher baseline CD5L concentration was associated with increased risk of CVE (HR, 95% CI, 1.17, 1.0-1.36), and all-cause mortality (1.22, 1.01-1.48) after adjusting for age, sex, diabetes, systolic blood pressure, dyslipidemia, waist circumference, smoking, and CKD stage. sCD36 showed no association with adverse CV outcomes or mortality. Our study showed for the first time that higher concentrations of CD5L are associated with future CVE and all-cause mortality in individuals with CKD.

Elevated levels of serum CD5 antigen-like protein distinguish secondary progressive multiple sclerosis from other disease subtypes.

CD5 antigen-like (CD5L) protein is a macrophage-secreted protein with roles in immunomodulation and lipid homeostasis. We compared serum CD5L levels in healthy controls to individuals diagnosed with clinically isolated syndrome, relapsing remitting (RR), secondary progressive (SP), and primary progressive (PP) multiple sclerosis (MS). CD5L was increased in SPMS relative to controls, RRMS, and PPMS. SPMS CD5L was associated with longer disease duration independent of age, sex, or disease severity. The positive relationship between CD5L and disease duration in SPMS suggests a chronic peripheral inflammatory profile compared to other subtypes, particularly PPMS, warranting investigation of functional roles for CD5L in MS.