Linking chronic infection and autoimmune diseases: Mycobacterium avium subspecies paratuberculosis, SLC11A1 polymorphisms and type-1 diabetes mellitus.
BACKGROUND
The 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.


RESULTS
Fifty 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
The 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.
Paccagnini
Daniela
D
Dipartimento di Scienze Biomediche, Sezione di Microbiologia clinica e sperimentale, Sassari, Italy.
Sieswerda
Lee
L
Rosu
Valentina
V
Masala
Speranza
S
Pacifico
Adolfo
A
Gazouli
Maria
M
Ikonomopoulos
John
J
Ahmed
Niyaz
N
Zanetti
Stefania
S
Sechi
Leonardo A
LA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics* / Q000382:microbiology*; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D003713:Dendritic Cells / Q000378:metabolism; D048909:Diabetes Complications / Q000235:genetics / Q000382:microbiology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000382:microbiology*; D005260:Female; D006801:Humans; D007239:Infections / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016927:Mycobacterium avium subsp. paratuberculosis / Q000378:metabolism*; D011110:Polymorphism, Genetic; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1