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Detection of Mycobacterium avium Subspecies paratuberculosis in the Blood of Patients with Rheumatoid Arthritis by Using Serological and Molecular Techniques

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Abstract

The role of Mycobacterium avium subspecies paratuberculosis (MAP) in triggering rheumatoid arthritis (RA) could be a population-specific phenomenon. This study explored the relationship between MAP and RA using serological and molecular techniques; In this case–control study, 239 Iranian participants, including 120 RA patients and 119 controls, were enrolled. The indirect ELISA was designed to diagnose antibodies against MAP3865c125-133 and Zinc transporter 8 (ZnT8)178–186. The Nested-Polymerase Chain Reaction (PCR) detected MAP in blood; The frequency of MAP in RA patients and controls was 31.9% and 12.5%, respectively (P = 0.002). The antibodies against MAP3865c125-133 and ZnT8178–186 were 42.9% and 37% in RA patients and 14.2% and 11.7% in the controls, respectively (P < 0.0001). Interestingly, positive ELISA results in previously diagnosed (PD) RA were more common than newly diagnosed (ND) RA patients (P < 0.05).; The findings showed a higher frequency of MAP and its antibodies in the RA patients than in the controls. This data indicated MAP as one of RA’s predisposing factors. Also, this first report implies the high positivity of MAP in Iranian RA patients.

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Data Availability

Data transparency is provided.

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Abbreviations

MAP:

Mycobacterium avium Subspecies paratuberculosis

RA:

Rheumatoid arthritis

ELISA:

Enzyme-linked immunosorbent assay

PCR:

Polymerase chain reaction

ZnT8:

Zinc transporter 8

ND:

Newly diagnosed

PD:

Previously diagnosed

ACPA:

Anti-citrullinated protein/peptide antibody

DMARD:

Disease-modifying anti-rheumatic drugs

NSAIDs:

Non-steroidal anti-inflammatory drugs

JD:

John’s disease

ParaTB:

Paratuberculosis

PknG:

Protein kinase G

MALT:

Mucosa-associated lymphoid tissue

T1D:

Type 1 diabetes

MS:

Multiple Sclerosis

SLE:

Systemic lupus erythematosus

PtpA:

Protein tyrosine phosphatase A

TMB:

3,3′,5,5′-Tetramethylbenzidine

RT:

Room temperature

RF:

Rheumatoid factor

BMI:

Body mass index

IS900:

Insertion sequence 900

OD:

Optical density

CRP:

C-reactive-protein

ESR:

Erythrocyte sedimentation rate

PBS:

Phosphate-buffered saline

HRP:

Horseradish peroxidase

anti-CCP:

Anti-cyclic citrullinated peptide

HCs:

Healthy controls

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Acknowledgements

This project was done as an MSc thesis of the first author in medical microbiology [Project number: 112501]. The authors would like to thank the personnel of the Department of Microbiology and other project colleagues at Golestan University of Medical Sciences, Gorgan, Iran, for the technical services.

Funding

Golestan University of Medical Sciences supported this study (Project number: 112501).

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Authors and Affiliations

  1. Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgān, Iran

    Negar Asgari, Ezzat Allah Ghaemi, Hadi Razavi Nikoo & Samin Zamani

  2. Rheumatology Research Center, Golestan University of Medical Sciences, Gorgān, Iran

    Samaneh Tavasoli & Mehrdad Aghaei

  3. Department of Biomedical Sciences, Azienda Ospedaliera Universitaria, University of Sassari, Viale San Pietro 43B, 07100, Sassari, Italy

    Leonardo Antonio Sechi

  4. Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgān, Iran

    Samin Zamani

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  1. Negar Asgari
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Contributions

NA is the first author who performed all laboratory experiments and sample collection, collected and analyzed data, and drafted the manuscript. EG and LAS participated in the coordination and advised in all parts of the study. ST and MA are rheumatologists who diagnosed and validated patients with RA and provided the specimens from all cases. HRN participated in the design and setup of the ELISA test. SZ participated in the study design and coordination and supervised all study parts and drafted the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Samin Zamani.

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Conflict of interest

The authors declare no conflict of interest.

Ethical Approval

This project was approved by the Ethics Committee of Golestan University of Medical Sciences (No. IR.GOUMS.REC.1401.042).

Consent to Participate

The research was explained to all participants, and they were asked to sign an informed consent form. All participants had the right to exit the study at any time, and their data would not be included in the study. Both patients and control groups were asked to fill out a questionnaire containing demographic information.

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Asgari, N., Ghaemi, E.A., Tavasoli, S. et al. Detection of Mycobacterium avium Subspecies paratuberculosis in the Blood of Patients with Rheumatoid Arthritis by Using Serological and Molecular Techniques. Curr Microbiol 80, 359 (2023). https://doi.org/10.1007/s00284-023-03477-9

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