Increased seroreactivity to proinsulin and homologous mycobacterial peptides in latent autoimmune diabetes in adults

Abstract

Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressing form of immune-mediated diabetes that combines phenotypical features of type 2 diabetes (T2D) with the presence of islet cell antigens detected in type 1 diabetes (T1D). Heterogeneous clinical picture have led to the classification of patients based on the levels of antibodies against glutamic acid decarboxylase 65 (GADA) that correlate with clinical phenotypes closer to T1D or T2D when GADA titers are high or low, respectively. To date, LADA etiology remains elusive despite numerous studies investigating on genetic predisposition and environmental risk factors. To our knowledge, this is the first study aimed at evaluation of a putative role played by Mycobacterium avium subsp. paratuberculosis (MAP) as an infective agent in LADA pathogenesis. MAP is known to cause chronic enteritis in ruminants and has been associated with autoimmune disorders in humans. We analyzed seroreactivity of 223 Sardinian LADA subjects and 182 healthy volunteers against MAP-derived peptides and their human homologs of proinsulin and zinc transporter 8 protein. A significantly elevated positivity for MAP/proinsulin was detected among patients, with the highest prevalence in the 32-41-year-old T1D-like LADA subgroup, supporting our hypothesis of a possible MAP contribution in the development of autoimmunity.

Presence of Mycobacterium avium Subspecies paratuberculosis Monitored Over Varying Temporal and Spatial Scales in River Catchments: Persistent Routes for Human Exposure

“…Furthermore, its persistence in rivers, where abstraction occurs, is likely to sustain human exposure through domestic water supply, with potential health consequences of this animal pathogen which is linked to a number a number of possible health outcomes in addition to Crohn’s disease [41,44,45]. These include Parkinson’s disease, rheumatoid arthritis, neuromyelitis optica spectrum disorder, multiple sclerosis and type 1 diabetes myelitis [4,5,6,8,9,10,11,12,64,65] and given the broad range of diseases, and the possible impact on human health, then monitoring human exposure could be crucial in disease control.…”

“…Mycobacterium avium subspecies paratuberculosis ( Map ) is a very slow growing member of the Mycobacterium avium complex [1,2]. Map is recognised as a multi-host pathogen [3] and is now implicated in a wide range of diseases including Parkinson’s disease, rheumatoid arthritis, neuromyelitis optica spectrum disorder, multiple sclerosis and type 1 diabetes myelitis [4,5,6,7,8,9,10,11,12]. However, it is known to cause Johne’s disease which is a chronic inflammation of the intestine (JD) [3,13,14,15], which can affect many animal species including primates [3].…”

Pathogenesis, Molecular Genetics, and Genomics of Mycobacterium avium subsp. paratuberculosis, the Etiologic Agent of Johne’s Disease

“…The cross-reactivity of MAP antigens with those in humans, such as the zinc transporter 8 protein, may underlie the etiology of these diseases ( 89 ). MAP is also postulated to be involved in the progression of HIV infection and other immune dysfunction diseases: multiple sclerosis, sarcoidosis, type 1 and 2 diabetes mellitus, Hashimoto’s thyroiditis, and Parkinson’s disease ( 90 – 96 ). Over the years, several studies have investigated the role of MAP in CD with conflicting results ( 4 , 97 – 100 ).…”

Antibody response to homologous epitopes of Epstein-Barr virus, Mycobacterium avium subsp. paratuberculosis and IRF5 in patients with different connective tissue diseases and in mouse model of antigen-induced arthritis

“…Among environmental factors, viral and bacterial infections, including those caused by Epstein-Barr virus (EBV) [ 12 ], SSJ [ 13 ], SLE [ 14 ], SSc [ 15 ] and Mycobacterium avium subspecies paratuberculosis (MAP), have been associated with different autoimmune diseases and CTDs [ [16] , [17] , [18] , [19] , [20] , [21] ].…”