Innate immunity in latent autoimmune diabetes in adults

Abstract

Latent autoimmune diabetes in adults (LADA) is an autoimmune disease that shares some genetic, immunological and clinical features with both type 1 diabetes and type 2 diabetes. Immune cells including CD4 + T cells, CD8 + T cells, B cells, macrophages and dendritic cells (DCs) have been detected in the pancreas of patients with LADA and a rat model of LADA. Therefore, similar to type 1 diabetes, the pathogenesis of LADA may be caused by interactions between islet β-cells and innate and adaptive immune cells. However, the role of the immunity in the initiation and progression of LADA remains largely unknown. In this review, we have summarized the potential roles of innate immunity and immune-modulators in LADA development. Furthermore, we have examined the evidence and discussed potential innate immunological reasons for the slower development of LADA compared with type 1 diabetes. More in-depth mechanistic studies are needed to fully elucidate the roles of innate immune-associated genes, molecules and cells in their contributions to LADA pathogenesis. Undertaking these studies will greatly enhance the development of new strategies and optimization of current strategies for the diagnosis and treatment of the disease. K E Y W O R D Sautoimmune, diabetes mellitus, innate immune cells, innate immunity, latent autoimmune diabetes in adults | INTRODUCTIONLatent autoimmune diabetes in adults (LADA), also known as type 1.5 diabetes or slow-onset diabetes in adults, is an autoimmune disease that shares some genetic, immunological and clinical features with both type 1 diabetes and type 2 diabetes. [1][2][3][4][5] The disease was first described in 1983 6 and was defined as LADA in 1993. 7 Although LADA accounts for approximately 1.5%-14.2% of the type 2 diabetes population, 8-14 no unified criteria or management guidelines have existed for LADA. Recently, a panel of international experts defined a strategy for LADA management, which will be greatly helpful to the diagnosis and treatment of the disease in clinical practice. 15 GADA level is considered as the most valuable discriminatory parameter to predict the development of β-cell function in LADA. 16 Compared with low level of glutamic acid decarboxylase antibody (GADA), high level of GADA in LADA is associated with faster insulin progression, indicating that the presence of high level of GADA was a significant predictor of insulin requirement in LADA. 17 Our group also found that patients with high level of GADA showed a worse baseline and accelerated decline of β-cell function, 18 while the metabolic phenotypes and β-cell function in LADA patients with a low level of GADA were similar to that in type 2 diabetes patients. 19 It was reported that the presence of N-terminally truncated GAD65 autoantibody in individuals with adult-onset diabetes is associated with the clinical

Fatty Acid Profiles and Their Association With Autoimmunity, Insulin Sensitivity and β Cell Function in Latent Autoimmune Diabetes in Adults

“…It is interesting to study the reason why pancreas β cell failure progresses slower than classical t1dm. Many hypothetic views were proposed ( 56 ), such HLA genotypes, risk genotype of t2dm ( 57 ), distorted innate inflammation ( 30 ), etc. PUFA, especially n-3, n-6 PUFA are important precursors of specialized pro-resolving mediators (SPMs) ( 41 ).…”

“…High fatty fish intake not only associated decreased GADA development ( 46 ), but also decreased the incidence of LADA. Autoimmunity should be fine-tuned between proinflammatory and anti-inflammatory states ( 30 ). SPMs from n-3 and n-6 PUFA undergoing through different pathway results different SPMs specialized in modulation proinflammatory or anti-inflammatory actions.…”

“…Furthermore, this GWS found a new metabolic genetic locus (BFKFB3) that has been previously found associated with other autoimmune disease was also associated with LADA for the first time ( 29 ). Innate immunity studies in patients with LADA has shown inflammatory activity fell in between t1dm and t2dm ( 30 – 34 ).…”

Diagnostic camouflage: A case report on Latent autoimmune diabetics of adulthood

“…However, she was positive for both islet cell and glutamic acid decarboxylase antibodies. Our patients meet the requirements for diagnosis; onset age >30 years old, presence of islet cell antibodies, presence of GAD and need of insulin therapy [ 13 ]. In presence of an autoimmune disease like Graves Disease the physician should also closely keep suspicion for other autoimmune disease.…”

Host gene effects on gut microbiota in type 1 diabetes

“…Innate immunity plays an important role in defending against infection by sensing specific ligands derived from exogenous microorganisms to induce innate immune responses and shape adaptive immunity, eventually modulates β-cell autoimmunity[ 50 , 51 ]. Pattern recognition receptors (PRRs), an integral part of the innate immune system, act as a host protector from bacterial invasion via recognizing and binding bacterial components [ 52 ].…”