Abstract
ObjectiveLatent autoimmune diabetes in adults (LADA) is an autoimmune diabetes characterized by slowly progressive of β-cell function deterioration. Our previous finding demonstrated that neutrophil numbers and migration abilities display distinct levels in different types of diabetes, including LADA, whereas its pathological alterations in the development of LADA remain unknown. We aimed to investigate the changes in transcriptional levels of peripheral neutrophils in newly diagnosed LADA.MethodsPeripheral blood neutrophils were isolated from newly diagnosed LADA patients (n = 5) and age-and sex-matched healthy controls (n = 5). The Transcriptomic signature was determined by RNA sequencing (RNA-seq). Differentially expressed genes (DEG) were screened, followed by analyzing downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Real-time polymerase chain reaction (qPCR) was applied for validation in LADA patients (n = 9) and age-and sex-matched healthy controls (n = 18), including sequencing samples.ResultsCompared with controls, 4105 DEG were screened in LADA patients, including 2661 upregulated and 1444 downregulated DEG. In GO analysis, DEG are mainly involved in leukocyte degranulation, myeloid cell differentiation, and immune response-regulating signaling. The top enriched KEGG pathways included cytokine-cytokine receptor interaction, adhesion molecule signaling, nuclear factor-κB (NF-κB) signaling and Th17 cell differentiation. Consistent with RNA-seq results, SELL, ITGA4, ITGAM, NCF4, ARHGAP3, and CLDN15 are upregulated in neutrophils by qPCR.ConclusionThe present study results provided a profile of DEG in the newly diagnosed LADA of south China. Our study reveals an abnormality in neutrophil disposition at the transcriptional level in LADA. Several essential genes may be involved in of LADA’s pathological process, which may be useful to guide prediction for LADA and further investigation into the pathogenesis for this disease.
Highlights
Diabetes mellitus is a global concern that causes an enormous burden to society and individuals
Our study reveals an abnormality in neutrophil disposition at the transcriptional level in Latent autoimmune diabetes in adults (LADA)
Nine LADA patients diagnosed within one year were enrolled from the Second Hospital of Central South University, Changsha, China, and LADA were diagnosed according to the Chinese Diabetes Society (CDS) Consensus on diagnosis and treatment of LADA in 2012 [11]: 1) diabetes diagnosed according to the 1999 World Health Organization (WHO) criteria for diabetes [12]; 2) age at onset of diabetes of >18 years; 3) with one or more positive autoantibodies against b cell antigens including glutamic acid decarboxylase (GAD), insulinoma-associated protein 2 (IA2), or zinc transporter-8 (ZnT8); 4) insulin independence within the first six months after diagnosis
Summary
Diabetes mellitus is a global concern that causes an enormous burden to society and individuals. Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes with an older mean age at onset, slower rate of b-cell loss and longer period of insulin independence after onset when compared with type 1 diabetes (T1DM). Global epidemiological surveys have indicated that LADA accounts for 2%–12% of patients with diabetes mellitus, who have more severe diabetic complications and a worse prognosis [2]. Compared to T1DM, less intense autoimmune attack on b-cells and a relatively long window period from onset to b-cell depletion are usually found in LADA. This delayed progression period provides a valuable opportunity for endocrinologists to understand the pathological mechanisms of autoimmune destruction of b-cells
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