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

Abstract

Introduction: Recent findings propose that Mycobacterium avium subsp. paratuberculosis (MAP) infection could act as risk factor in favoring multiple sclerosis (MS) progression. SLC11A1 is a gene associated with mycobacterial survival in the host and it may be involved in the induction and maintenance of autoimmune disease. Methodology: In this preliminary study, 100 MS patients and 100 healthy controls (HCs) from Sardinia were enrolled. Eight single nucleotide polymorphisms (SNPs) in the SLC11A gene were searched by PCR RFLP-genotyping. IS900 specie specific PCR was undertaken to search for MAP presence. Indirect ELISA was performed to asses if MS patients displayed a stronger humoral response against MAP2694 protein compared to the HCs. Results: Only rs2276631 SNP was associated with MS. MAP DNA was detected in 23 out of 100 MS patients (23%) and in 7 out of 100 HCs (7%). A strong humoral response against MAP2694 protein was detected in 36% of MS patients and only in 3% of HCs. A correlation between ELISA sero-positivity and the rs2276631 SNP was also found. Conclusion: Our preliminary results suggest that the Sardinian population might be prone to develop autoimmune disease due to polymorphisms in immunomodulating the SLC11A1 gene, which is important in the immune response against intracellular bacteria such as MAP.

Mycobacterium avium ss. paratuberculosis Zoonosis – The Hundred Year War – Beyond Crohn’s Disease

“…In addition to leprosy (76) and tuberculosis (77), an association is found in rheumatoid arthritis (78), MS (39, 79), inflammatory bowel disease (80–82), and type 1 diabetes – all diseases associated with MAP (83, 84). …”

“…Sechi et al have published studies implicating MAP in MS (37–39, 41–49). Molecular mimicry and SLC11A1 associations are central to this association as well (40, 41).…”

Susceptibility of autoimmune diseases in three polymorphisms of infection-associated gene IRAK1

“…The sustained pathology of ADs is directly caused by a specific self-reactive immune response, including innate and adaptive immune response, which can be caused by infection with some kinds of pathogenic microorganisms [5][6][7]. Interleukin-1 (IL-1) receptorassociated kinases (IRAKs) are key mediators in the signaling pathways of innate immune response, especially in the Toll-like receptors (TLRs)/IL-1 receptors (IL-1Rs) pathway.…”

Anti Mycobacterium avium subsp. paratuberculosis heat shock protein 70 antibodies in the sera of Sardinian patients with multiple sclerosis

“…paratuberculosis (MAP) presence to MS disease [6][7][8][9][10]. The association was observed and explained in light of the molecular mimicry theory, and it is sustained by two major pieces of evidence: the presence of a strong humoral response against MAP specific antigens and the detection of MAP DNA in the peripheral blood mononuclear cells (PBMCs) of MS patients.…”

“…Indeed, quite a few lines of evidence point out that MAP could act as a risk factor in the development of these two autoimmune disease [6][7][8][9][10]. …”