Tetraspanin 7 autoantibodies predict progressive decline of beta cell function in individuals with LADA

Abstract

Aims/hypothesis The aim of this work was to investigate whether tetraspanin 7 autoantibodies (TSPAN7A) are valuable in predicting poor beta cell function in individuals with latent autoimmune diabetes in adults (LADA). Methods The cross-sectional study involved participants with LADA (n = 173), type 1 diabetes (n = 158), type 2 diabetes (n = 204) and healthy control participants (n = 170). The longitudinal study involved 53 participants with LADA, with a 3-year follow-up. In both cohorts, TSPAN7A in the sera were measured by a luciferase immunoprecipitation system assay, and physical and clinical characteristics were recorded. Results The prevalence of TSPAN7A in LADA, type 1 diabetes, type 2 diabetes and healthy control participants was 21.4% (37/ 173), 26% (41/158), 0.5% (1/204) and 1.2% (2/170), respectively. Importantly, measurement of TSPAN7A significantly increased the number of individuals with LADA found to be positive for multiple antibodies (32.4% vs 22%; p < 0.001). Further logistic regression analysis demonstrated that positivity for TSPAN7A (OR 2.87, p = 0.034), disease duration (OR 1.83, p = 0.019) and GAD antibody titre (OR 2.67, p = 0.009) were risk factors for beta cell function in LADA, while BMI (OR 0.34, p = 0.001) was a protective factor. In the prospective study in individuals with LADA, the median annual decrease in rates of fasting C-peptide and 2 h postprandial C-peptide in individuals who were positive for TSPAN7A was significantly higher when compared with the decrease in those who were negative for TSPAN7A (34.6% vs 7.9%, p = 0.043 and 33.2% vs 11%, p = 0.041, respectively). Conclusions/interpretation TSPAN7A are valid islet autoantibodies for use in East Asian populations with autoimmune diabetes and can discriminate individuals with LADA who have lower beta cell function after disease progression.

Follicular helper T cells in type 1 diabetes

“…46,47 All these antibodies are secreted by longlived plasma cells, which are considered to be generated from GCs with the help of Tfh cells, suggesting the aberrant differentiation and function of Tfh cells in T1D patients. So far six major autoantibodies have been identified in T1D: islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA), insulin antibodies (IAA), protein tyrosine phosphatase autoantibodies (IA-2A), zinc transporter 8 antibodies (ZnT8A), and the newly identified tetraspanin 7 antibodies (TSPAN7A).…”

“…Indeed, antigen-experienced memory CD4 + T cells in the blood of T1D patients highly expressed CXCR5, PD-1, ICOS and IL-21, possessing the profile of Tfh. 46,47 Yang and colleagues found that more Tfh cells and elevated levels of IL-21 were observed in ZnT8A or IA-2A-positive T1D patients, which could be reversed after anti-CD20 monoclonal antibody (rituximab) treatment, indicating the essential role of B cells in the maintenance of Tfh cells. Intriguingly, the increase of Tfh cells only occurred in multiple-antibody positive at-risk children.…”

“…So far six major autoantibodies have been identified in T1D: islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA), insulin antibodies (IAA), protein tyrosine phosphatase autoantibodies (IA-2A), zinc transporter 8 antibodies (ZnT8A), and the newly identified tetraspanin 7 antibodies (TSPAN7A). 46,47 All these antibodies are secreted by longlived plasma cells, which are considered to be generated from GCs with the help of Tfh cells, suggesting the aberrant differentiation and function of Tfh cells in T1D patients. Indeed, antigen-experienced memory CD4 + T cells in the blood of T1D patients highly expressed CXCR5, PD-1, ICOS and IL-21, possessing the profile of Tfh.…”

Organ-specific autoantibodies in Chinese patients newly diagnosed with type 1 diabetes mellitus

“…A previously established luciferase immunoprecipitation system assay (LIPS) was used for TSPAN7A testing [4]. Briefly, the TSPAN7-luciferase fusion protein was expressed in 293T cells.…”

The potential application of Cordyceps in metabolic‐related disorders

“…T1DM is an organ‐specific autoimmune disease characterized by T cell‐mediated islet β cell devastation leading to an absolute insulin deficiency (Shi et al, ; Yang et al, ; Zheng et al, ). The preventive effect of FTY720 on autoimmune diabetes was studied in nonobese diabetic mice, a well‐established animal model of spontaneous T1DM.…”