Latent Autoimmune Diabetes in Adults (LADA): From Immunopathogenesis to Immunotherapy

Abstract

Latent autoimmune diabetes in adults (LADA) is a type of diabetes characterized by slow autoimmune damage of pancreatic β cells without insulin treatment in the early clinical stage. There are differences between LADA and classical type 1 diabetes (T1D) and type 2 diabetes (T2D) in genetic background, autoimmune response, rate of islet function decline, clinical metabolic characteristics, and so on. The disease progression and drug response of patients with LADA are closely related to the level of islet autoimmunity, thus exploring the pathogenesis of LADA is of great significance for its prevention and treatment. Previous studies reported that adaptive immunity and innate immunity play a critical role in the etiology of LADA. Recent studies have shown that the intestinal microbiota which impacts host immunity hugely, participates in the pathogenesis of LADA. In addition, the progression of autoimmune pancreatic β cell destruction in LADA is slower than in classical T1D, providing a wider window of opportunities for intervention. Therefore, therapies including antidiabetic drugs with immune-regulation effects and immunomodulators could contribute to promising interventions for LADA. We also shed light on potential interventions targeting the gut microbiota and gut-associated immunity, which may be envisaged to halt or delay the process of autoimmunity in LADA.

Keywords: adaptive immunity; gut-associated immunity; immunopathogenesis; immunotherapy; innate immunity; latent autoimmune diabetes in adults.

Figure 1

Immunity activates latent autoimmune diabetes in adults (LADA) and immunomodulatory therapies. The pathogenesis of LADA is the result of the interaction of innate immunity, adaptive immunity, and gut-associated immunity. Macrophages and CD8⁺ T cells are the most abundant immune cells infiltrating in the insulitis of LADA patients. In addition, other immune cells such as NK cells, neutrophils, CD4⁺ T cells, and B cells were also found to be involved in the development of LADA. A variety of corresponding immunomodulatory therapies have been developed.