Humoral Immune Responses of Type 1 Diabetes Patients to Mycobacterium avium subsp. paratuberculosis Lend Support to the Infectious Trigger Hypothesis

Abstract

Mycobacterium avium subsp. paratuberculosis is a zoonotic pathogen whose association with Crohn's disease in humans is under scrutiny. The objective of this work was to investigate its association with other chronic diseases such as type 1 diabetes mellitus (T1DM), where the involvement of a persistent pathogen such as M. avium subsp. paratuberculosis could be the trigger. For this purpose, 59 diabetic patients and 59 healthy controls were investigated for the presence of antibodies against two recombinant proteins of M. avium subsp. paratuberculosis and the whole-cell lysate. Extremely significant humoral immune responses to recombinant heparin binding hemagglutinin and glycosyl transferase proteins and the whole-cell lysates of M. avium subsp. paratuberculosis bacilli were observed in T1DM patients and compared to those of healthy controls. Finding evidence of M. avium subsp. paratuberculosis involvement in T1DM is perhaps a novel finding that might serve as a foundation stone in establishing an infectious etiology for T1DM.Immune-related disorders are frequently rampant in both developed and developing countries. It is speculated that such diseases probably reflect and connect to long-term effects of a change in lifestyle and thereby a reduced exposure to certain bacteria that have been inherently associated with human societies during most of mammalian evolution (3,17). A very important group of bacteria among these organisms is saprophytic mycobacteria, which trigger regulatory immune cell populations (3, 17) such as cytokine-secreting and antigenpresenting cells. These immune cell populations are probably the deterrent to some autoimmune diseases such as type 1 (insulin-dependent) diabetes mellitus (T1DM).T1DM constitutes interactions of polygenic traits with notwell-known environmental factors, and it is not known what triggers autoimmunity to self-antigens such as those expressed in the pancreatic islets of Langerhans cells (5, 11). Drinking of cow's milk in childhood is assumed to be a risk factor for the development of this disease (17). The role of mycobacterial proteins that cross-react with epitopes of human cell surface molecules has been explored (3, 5).Human populations that lived hygienic lifestyles and therefore remained "sanitized" for decades might react aggressively to exposure to certain microbial communities such as Mycobacterium avium subsp. paratuberculosis. Due to the expansion of the dairy industry in developed countries as a result of modern animal breeding, the exposure of human populations to M. avium subsp. paratuberculosis has increased. Sardinia, Italy, is one such example, where intensive sheep farming is practiced and the sheep population constitutes more than four times the existing human population of this Mediterranean island.M. avium subsp. paratuberculosis bacilli have been notoriously known to trigger molecular mimicry (15,23). It has long been a belief that genetic susceptibilities, epitope homologies, and endemic bacterial load in the environment might support the case ...

First mass screening of the human population to estimate the bio-load of Mycobacterium avium subspecies paratuberculosis in North India

“…However, recent advancements in MAP research indicated the presence and role of MAP in patients with various diseases such as Type-1 Diabetes (Sechi et al, 2008), autoimmune thyroiditis (D"Amore et al, 2010), multiple sclerosis (Cossu et al, 2013a), autism (Dow, 2011), sarcoidosis (EL-Zaatari et al, 1996) and autoimmune arthritis (Moudgil et al, 1997). Our study correlates with the finding of some authors that have claimed the association of MAP infection with autoimmune disorder viz.…”

“…MAP has also been associated with Type-1 Diabetes (Sechi et al, 2008), autoimmune thyroiditis (D"Amore et al, 2010), multiple sclerosis (Cosu et al, 2013a), autism (Dow, 2011), sarcoidosis (EL-Zaatari et al, 1996), rheumatoid arthritis (Moudgil et al, 1997), autoimmune hepatitis (Miyata et al, 1995), primary biliary cirrhosis (Vilagut et al, 1997), scleroderma (Danieli et al, 1992), Kawasaki disease (Yokota et al, 1993), Behcet"s disease (Direskeneli and Saruhan-Direskeneli, 2003) and Takayasu"s arteritis (Aggarwal et al, 1996). Information Vir Singh et al 21 on the association of MAP with different human health problems is yet to be recognized and taken seriously by the medical doctors and scientists in India.…”

Recent Approaches in Diagnosis and Control of Mycobacterial Infections with Special Reference to Mycobacterium Avium Subspecies

“…The approximate economic loss due to paratuberculosis per sheep/farmer/year is around Rs 1,840 (US$ 38.33) in India (Vinodhkumar et al, 2013). There are evidences to relate MAP with human diseases like Crohn's disease (Greenstein, 2003) and type I diabetes (Naser et al, 2013, Sechi et al, 2008. As MAP is not killed by pasteurization , milk is considered as vehicle of transmission of MAP to humans.…”

Chlamydia pneumoniae infection in adolescents with type 1 diabetes mellitus

“…C. pneumoniae establishes a latent infection in some cell types, with life-long persistence of the bacteria in the infected body, participating in the formation of atherosclerotic plaques and potentiating the inflammatory reaction at the site of infection (Roubalová et al, 2007). It can establish persistent infection in macrophages, associated with an alteration of their function, and can modulate the host immune response (Roubalová et al, 2007;Bulut et al, 2002); these immune cell populations are probably the deterrent to some autoimmune diseases such as T1DM (insulin-dependent) (Sechi et al, 2008).…”