Linking Chronic Infection and Autoimmune Diseases: Mycobacterium avium Subspecies paratuberculosis, SLC11A1 Polymorphisms and Type-1 Diabetes Mellitus

Abstract

BackgroundThe etiology of type 1 diabetes mellitus (T1DM) is still unknown; numerous studies are performed to unravel the environmental factors involved in triggering the disease. SLC11A1 is a membrane transporter that is expressed in late endosomes of antigen presenting cells involved in the immunopathogenic events leading to T1DM. Mycobacterium avium subsp. paratuberculosis (MAP) has been reported to be a possible trigger in the development of T1DM.Methodology/Principal FindingsFifty nine T1DM patients and 79 healthy controls were genotyped for 9 polymorphisms of SLC11A1 gene, and screened for the presence of MAP by PCR. Differences in genotype frequency were evaluated for both T1DM patients and controls. We found a polymorphism in the SLC11A1 gene (274C/T) associated to type 1 diabetic patients and not to controls. The presence of MAP DNA was also significantly associated with T1DM patients and not with controls.Conclusions/SignificanceThe 274C/T SCL11A1 polymorphism was found to be associated with T1DM as well as the presence of MAP DNA in blood. Since MAP persists within macrophages and it is also processed by dendritic cells, further studies are necessary to evaluate if mutant forms of SLC11A1 alter the processing or presentation of MAP antigens triggering thereby an autoimmune response in T1DM patients.

Detection of Mycobacterium avium subsp. paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA

“…However, Rani et al could not find any association despite the high prevalence of MAP and T1DM in India, probably due to the low number of patients investigated [21] or the genetic predisposition of the infected population in developing such an autoimmunity. Moreover, Paccagnini et al reported the association of the SLC11A1 gene in the Sardinian population either with T1DM or susceptibility to mycobacterial infection [20].…”

“…In addition, MAP has been suggested as a possible cause of T1DM. The association of T1DM and MAP has been observed in the Sardinian population (Italy) [19,20], but a recent study could not replicate this finding in India, probably due to the small number of investigated samples [21].…”

Association of Mycobacterium avium subsp. paratuberculosis and SLC11A1 polymorphisms in Sardinian multiple sclerosis patients

“…Furthermore, a correlation between ELISA sero-positivity and SNP presence in 20% of the cases was observed. The association between rs2276631 SNP and Type 1 diabetes was recently reported [7], suggesting that the same polymorphism may be common to the major autoimmune diseases widespread in Sardinia.…”

“…Genomic DNA was purified from whole blood according to standard procedures [7]. Eight polymorphisms (rs2276631, rs3731865, rs3731864, rs17221959, rs2695342, rs2279015, rs17235409, rs17235416) were genotyped by PCR restriction fragment length polymorphism (RFLP) analysis, and the set of specific primers were designed based on the GenBank reference sequence (accession no.…”

Probiotics Applications in Autoimmune Diseases

“…Previous figures underestimated the scope of the problem, while even the most pessimistic predictions fell short of the current figure. It is predicted that the total number of people living with AD will increase drastically within the coming thirty years if no new and substantially more effective drugs are produced [4]. On 2009, estimated health costs of autoimmune disorders have exceeded 100 billion dollars only in the US.…”