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1.
Int J Inflam ; 2017: 7959154, 2017.
Article in English | MEDLINE | ID: mdl-28523203

ABSTRACT

Background. The prevalence of allergies is steadily increasing worldwide; however, the pathogenesis is still unclear. We hypothesized that Mycobacterium avium subsp. paratuberculosis (MAP) may contribute to allergy development. This organism can be present in dairy foods, it can elicit an immunomodulatory switch from a Th1 to a Th2 response, and it has been speculated that it is linked to several human autoimmune diseases. To determine the contribution, sera from 99 individuals with various atopic disorders and 45 healthy nonallergic controls were assessed for total IgE levels and successively for MAP-specific IgE by ELISA. Results. The mean total serum IgE level in allergic patients was 256 ± 235 IU/mL, and in the healthy controls it was 62 ± 44 IU/mL (AUC = 0.88; p < 0.0001). Among the patient groups, 50 of the 99 subjects had increased IgE total level ≥ 150 IU/mL, while 49 subjects had IgE ≤ 150 IU/mL (mean level: 407 ± 256 IU/mL versus 106 ± 16 IU/mL; p < 0.0001). Additionally, 6 out of 50 subjects (12%) with IgE ≥ 150 IU/mL and none (0%) with IgE ≤ 150 IU/mL were positive for specific MAP IgE (AUC = 0.63; p = 0.03). Conclusion. The present study revealed that MAP has the ability to induce specific IgE and might contribute to the induction of allergic inflammation in genetically predisposed individuals.

2.
Clin Exp Immunol ; 189(1): 127-131, 2017 07.
Article in English | MEDLINE | ID: mdl-28324619

ABSTRACT

Endogenous retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been reported recently to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su19-37 , env-su109-126 , env-su164-186 , env-su209-226 ) were selected by bioinformatic analysis on the basis of their putative immunogenicity. Indirect enzyme-linked immunosorbent assay (ELISA) was then carried out to quantify antibodies against those peptides on blood samples of 70 consecutive RA patients and 71 healthy controls (HC). Differences between the two groups were analysed using the Mann-Whitney test. Potential correlations between RA laboratory, clinical descriptors and immunoglobulin (Ig)G levels were explored by bivariate regression analysis. Serum autoantibodies against one of four tested peptides of HERV-K (env-su19-37 ) were significantly higher in RA than in HC (19 versus 3%, P = 0·0025). Subgroup analysis showed no association between anti-HERV-K peptide humoral response and clinical, serological and clinimetric RA disease descriptors. Serum from RA patients in our series reacted significantly against HERV-K env-su19-37 peptide in comparison to the general population suggesting a role for the HERV-K- related, secondary antigenic-driven immune response in the pathogenesis of RA. Further studies are needed to confirm these results and to explore the role of this HERV-K surface peptide as a potential therapeutic target.


Subject(s)
Arthritis, Rheumatoid/immunology , Endogenous Retroviruses/immunology , Viral Envelope Proteins/immunology , Adult , Aged , Antibodies, Viral/blood , Arthritis, Rheumatoid/blood , Autoantibodies/blood , Case-Control Studies , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunity, Humoral , Immunoglobulin G/blood , Male , Middle Aged , Peptides/immunology
3.
BMC Neurol ; 16(1): 148, 2016 Aug 23.
Article in English | MEDLINE | ID: mdl-27552900

ABSTRACT

BACKGROUND: Amongst Sardinians the human leukocyte antigen (HLA) DRB1-DQB1 haplotypes *15:02-*06:01, *16:01-*05:02, *14:01-4-*05:03 are protective for multiple sclerosis (MS), while *13:03-*03:01, *04:05-*03:01, *03:01-*02:01, *15:01-*06:02 and Mycobacterium avium subspecies paratubercolosis (MAP) are predisposing factors. We studied the correlation between MAP and HLA. METHODS: Five hundred thirty-one patients were searched for anti-MAP2694 antibodies, DRB1-DQB1 genotyping was performed. The haplotypes were classified as predisposing, neutral or protective. RESULTS: Anti-MAP2694 were found in 23 % of subjects carrying one protective HLA versus 32 % without (p = 0.04). CONCLUSIONS: We showed a lower frequency of Abs in patients with protective HLA. These haplotypes could have a protective role for both MS and MAP.


Subject(s)
HLA-DQ beta-Chains/immunology , HLA-DRB1 Chains/immunology , Multiple Sclerosis/immunology , Mycobacterium avium/immunology , Adult , Antibodies/immunology , Female , Genotype , Haplotypes , Humans , Male , Risk Factors
4.
Eur J Neurol ; 23(1): 140-7, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26453465

ABSTRACT

BACKGROUND AND PURPOSE: Infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) has been associated with increased risk of multiple sclerosis (MS). However, the mechanism linking these pathologies is unclear. Different reports indicate the association of EBV, and recently Mycobacterium avium subsp. paratuberculosis (MAP), with MS. For a better understanding of the role of these pathogens, the host response induced by selected antigenic peptides in subjects with a history of IM that significantly increases the risk of MS was investigated. METHODS: Both humoral and cell-mediated response against peptides able to induce a specific immune activation in MS patients deriving from lytic and latent EBV antigens BOLF1(305-320), EBNA1(400-413), from MAP MAP_4027(18-32), MAP_0106c(121-132) and from human proteins IRF5(424-434) and MBP(85-98) in subjects with current and past IM were examined. RESULTS: EBNA1 and MAP_0106c peptides were able to induce a humoral immune response in subjects with a history of clinical IM in an independent manner. Moreover, these peptides were capable of inducing pro-inflammatory cytokine interferon γ by CD4+ and CD8+ T lymphocytes and interleukin 6 and tumour necrosis factor α by CD14+ monocyte cells. CONCLUSION: Our results highlight that EBV and MAP may be involved independently in the same causal process leading to MS in subjects with a history of IM.


Subject(s)
Herpesvirus 4, Human/immunology , Infectious Mononucleosis/immunology , Multiple Sclerosis/immunology , Mycobacterium avium subsp. paratuberculosis/immunology , Adult , Epstein-Barr Virus Nuclear Antigens/immunology , Female , Humans , Infectious Mononucleosis/complications , Male , Multiple Sclerosis/etiology , Peptides/immunology , Young Adult
5.
Clin Rheumatol ; 33(12): 1725-9, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24859782

ABSTRACT

Little is known regarding the environmental factors at play in igniting rheumatoid arthritis (RA) autoimmunity, although an association between Mycobacteria and RA has been documented. This pilot study focused on examining a possible involvement of Mycobacterium tuberculosis (MTB) and Mycobacterium avium ss. paratuberculosis (MAP) in RA. We measured out the serum levels of IgG antibody against different mycobacterial antigens in Sardinian patients and controls, by an enzyme-linked immunosorbent assay. The population study was composed of 61 RA patients under different therapies and 52 healthy controls, whereas the antigens tested were MTB lipoarabinomannan (ManLAM), MAP heath shock protein 70, and MAP protein tyrosine phosphatase. The frequencies of anti-ManLAM antibodies were higher in the RA group (23 %) compared to the healthy controls (5.7 %) (AUC = 0.7; p < 0.0001), whereas serum reactivity to MAP antigens was not observed. ManLAM antigen was also detected in the plasma of three RA patients (which were anti-ManLAM antibody positive) by Western blot analysis using anti-Man-LAM monoclonal antibodies. The data produced corroborate the hypothesis of a potential association between MTB ManLAM and RA disease, but so far, further studies are necessary to understand its role in RA pathogenesis.


Subject(s)
Antibodies, Bacterial/immunology , Arthritis, Rheumatoid/ethnology , Arthritis, Rheumatoid/immunology , Lipopolysaccharides/immunology , Mycobacterium tuberculosis , Aged , Antibodies, Monoclonal/immunology , Antigens, Bacterial/chemistry , Arthritis, Rheumatoid/complications , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , HSP70 Heat-Shock Proteins/chemistry , Humans , Immunoglobulin G/blood , Italy , Latent Tuberculosis/complications , Latent Tuberculosis/microbiology , Lipopolysaccharides/chemistry , Male , Middle Aged , Mycobacterium avium subsp. paratuberculosis , Pilot Projects , Protein Tyrosine Phosphatases/chemistry
6.
J Neurol Sci ; 335(1-2): 131-3, 2013 Dec 15.
Article in English | MEDLINE | ID: mdl-24075312

ABSTRACT

Heat shock protein (HSP) family members are highly conserved in both prokaryotic and eukaryotic organisms and are known to be immunodominant antigens in many bacteria. In particular, HSP70 has been linked to multiple sclerosis (MS), even if the available data are contradictory. Since different studies conducted on Sardinian subjects, have linked Mycobacterium avium subspecies paratuberculosis (MAP) presence to MS disease, and in view of the fact that human HSP70 is highly homologue to the majority of mycobacterial HSP70 proteins, we searched for anti-MAP HSP70 antibodies in the sera of 268 MS patients and 231 age and sex-matched healthy controls (HCs). All the subjects enrolled in the study were from Sardinia, which is an excellent setting for investigation since it has one of the highest prevalence of MS worldwide. HSP70 detection was carried out using ELISA methodology. A statistically significant difference was found between MS patients and HCs when analyzing the humoral response mounted against MAP HSP70 protein. Our study confirms that mycobacterial HSP70 might be involved in MS, and provides another piece of evidence sustaining the role played by MAP in MS in the context of Sardinian population.


Subject(s)
Antibodies/blood , HSP70 Heat-Shock Proteins/immunology , Multiple Sclerosis/blood , Mycobacterium avium subsp. paratuberculosis/immunology , Adult , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Italy/epidemiology , Male , Middle Aged , Mycobacterium avium subsp. paratuberculosis/genetics , Mycobacterium avium subsp. paratuberculosis/metabolism
7.
Mult Scler ; 19(11): 1437-42, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23439580

ABSTRACT

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) is an infectious factor recently found in association with multiple sclerosis (MS) in Sardinia. OBJECTIVES: The objectives of this study were to confirm this association and evaluate its role in clinical features. METHODS: A total of 436 patients and 264 healthy controls (HCs) were included. We examined the blood of each individual for MAPDNA and MAP2694 antibodies using IS900-specific PCR and ELISA, respectively. Differences in MAP presence between the MS group and HCs were evaluated. In MS patients, we considered: gender, age, age at onset, duration of disease, course, EDSS, therapy, relapse/steroids at study time, and oligoclonal bands (OBs). RESULTS: MAPDNA and MAP2694 antibodies were detected in 68 MS and six HCs (p = 1.14 × 10(-11)), and 123 MS and 10 HCs (p = 2.59 × 10(-23)), respectively. OBs were found with reduced frequency in MAP-positive patients (OR = 0.52; p = 0.02). MAP2694 antibodies were detected more in patients receiving MS treatments (OR = 2.26; p = 0.01), and MAPDNA in subjects on steroids (OR = 2.65; p = 0.02). CONCLUSION: Our study confirmed the association of MAP and MS in Sardinia. The low OB frequency in MAP patients suggests a peripheral role as a trigger in autoimmunity. MAP positivity might be influenced by steroids and MS therapy. Studies in other populations are needed to confirm the role of MAP in MS.


Subject(s)
Multiple Sclerosis/microbiology , Mycobacterium avium subsp. paratuberculosis , Paratuberculosis/epidemiology , Adult , Antibodies, Bacterial/blood , DNA, Bacterial/analysis , Enzyme-Linked Immunosorbent Assay , Female , Humans , Italy/epidemiology , Male , Multiple Sclerosis/blood , Mycobacterium avium subsp. paratuberculosis/immunology , Paratuberculosis/blood , Polymerase Chain Reaction
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