Elevated Layilin-Positive Monocyte Levels in the Peripheral Blood of Patients with Systemic Lupus Erythematosus Reflect Their Autoimmune Status

ABSTRACTObjective To investigate the expression of layilin (LAYN) in human circulating monocytes and lymphocytes and its clinical significance in systemic lupus erythematosus (SLE).Methods Blood samples were collected from 51 SLE patients and 50 healthy controls. Flow cytometry was used to analyze LAYN in lymphocytes and monocyte subsets. Functionally characterized molecules including human HLA, CD74 and CD62L were studied in LAYN+ monocytes. A correlation analysis was conducted between LAYN-related subsets and clinical indicators of SLE such as anti-double-stranded DNA and complements levels. ROC curves were used to explore the potential clinical diagnostic value of LAYN in SLE.Results LAYN was significantly higher in monocytes than in lymphocytes and higher in CD14+CD16+ monocytes than in CD14-CD16+ and CD14+CD16- monocytes. CD74 was upregulated and CD62L was downregulated in LAYN+ monocytes compared with LAYN- monocytes. The absolute number of LAYN+ monocytes was increased in SLE patients, and the median fluorescence intensity of HLA was decreased. LAYN+ monocytes were positively correlated with complement C4, while decreased CD62L+ percentages in LAYN+ monocytes were negatively correlated with C4. The ROC analysis revealed that the area under the curve (AUCs) for CD62L+ percentages in LAYN+ monocytes, LAYN+ lymphocyte numbers, and LAYN+ monocyte numbers to distinguish SLE from healthy individuals were 0.6245, 0.6196 and 0.6173, respectively.Conclusion LAYN is differentially expressed in monocytes and their subpopulations and has corresponding functional differences. Changes in LAYN expression on monocytes are associated with complement C4 levels in SLE patients. These suggest that LAYN may be involved in the pathogenesis of SLE.Abbreviation ANOVA: analysis of variance; anti-dsDNA: anti-double-stranded DNA; anti-ENA: anti-extractable nuclear antigen; anti-SSA: anti-Sjogren syndrome A; anti-SSB: anti-Sjogren syndrome B; anti-U1RNP: anti-U1 ribonucleoprotein; AUC: area under the ROC curve; CBC: complete blood count; CD62L: L-selectin; CD74/Ii: MHC class II invariant chain; CD44/HCAM: homing cell adhesion molecule; cMos: classical monocytes; CRP: C-reactive protein; CXCR2: C-X-C motif chemokine receptor 2; CXCR4: C-X-C motif chemokine receptor 4; ESR: erythrocyte sedimentation rate; HCs: healthy controls; HA: hyaluronan; HLA: human leukocyte antigen; Ig: immunoglobulin; iMos: intermediate monocytes; LAYN: layilin; MFI: median fluorescence intensity; MIF: migration inhibitory factor; ncMos: nonclassical monocytes; PBMCs: peripheral blood mononuclear cells; ROC: receiver operating characteristic curve; SLE: systemic lupus erythematosus; SLEDAI, SLE disease activity index; Treg: regulatory T cells; WBCs: white blood cells.KEYWORDS: Layilinlymphocytemonocytesystemic lupus erythematosus AcknowledgmentsWe are grateful to the Department of Rheumatology, Peking University People’s Hospital for sharing electronic medical records.Disclosure statementNo potential conflict of interest was reported by the author(s).Authors ContributorsCL took charge of all the work and participated in its design. CL and YW drafted the manuscript. CL, YW, YZ and ZY conducted most of the experiments and collected the data. ZZ and XZ performed some of the cellular experiments. ZG, AB and SL performed some of the clinical measurements. All authors read and approved the final manuscript.Supplementary materialSupplemental data for this article can be accessed online at https://doi.org/10.1080/08820139.2023.2249531.Additional informationFundingThis work was supported by grants from the National Natural Science Foundation of China [82271755, 81871230] and Peking University People’s Hospital Scientific Research Development Funds [RZ 2022-06].