Review
The roles of adenosine deaminase in autoimmune diseases

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Abstract

Autoimmune diseases patients are characterized by the autoimmune disorders, whose immune system can't distinguish between auto- and foreign- antigens. Thus, Immune homeostasis disorder is the key factor for autoimmune diseases development. Adenosine deaminase (ADA) is the degrading enzyme for an immunosuppressive signal - adenosine, and play an important role in immune homeostasis regulation. Increasing evidences have shown that ADA is involved in various autoimmune diseases. ADA activity were changed in multiple autoimmune diseases patients and could be served as a biomarker for clinical diagnosis. In this study, we analyze the change of ADA activity in patients with autoimmune diseases, and we underline its potential diagnostic value for autoimmune diseases patients.

Introduction

Autoimmune diseases are a complicated set of chronic diseases with unknown etiology, which are characterized by autoimmune tolerance deficiency. The imbalance of innate and adaptive immunity have been found to play important roles during autoimmune diseases progression [[1], [2], [3], [4]]. Immune system of autoimmune disease patients cannot distinguish self-antigens from foreign antigens, which leads to the abnormal immune response against self-tissues and organs. Thus, abundant autoantibodies were appeared in serum and organs of patients with autoimmune diseases [5,6]. Autoimmune diseases can be classified into organ-specific and systemic autoimmune diseases according to the location of lesions involved. Organ-specific autoimmune diseases means that lesions are confined to specific tissues or organs, such as myasthenia gravis (MG), ulcerative colitis (UC), primary biliary cirrhosis (PBC), etc. Systemic autoimmune diseases means that lesions can involve a variety of tissues and organs, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), dermatomyositis (JM), etc. Up to date, most types of the autoimmune diseases still lack the efficient laboratory markers. At present, there are several conventional markers commonly used in clinical, such as autoantibody, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid factor (RF). However, the specificity or sensitivity of these marker were still unsatisfactory. As an immune regulatory molecule, adenosine deaminase (ADA) has showed the potential clinical value in diagnosis and monitoring of autoimmune diseases.

Section snippets

Adenosine deaminase

ADA is an important immune regulatory molecule, which play an important role in maturation and maintenance of immune system [7,8]. It has well known that ADA deficiency could result to human severe combined immunodeficiency (SCID). SCID due to ADA deficiency was the first inherited disease treated with a gene transfer therapy approach [9,10]. Since the ADA deficiency could result to the immunodeficiency, then how are the effects or clinical significances of elevated ADA activity in human

ADA activity in SLE

SLE is a systemic and potentially also life-threatening autoimmune disease with unknown etiology, which affects almost all the tissues and organs, including skin, kidney, arthrosis, etc. SLE is more common in young and middle-aged women. Immune overreaction is an key factor and feature for SLE development, thus, immunosuppressive therapy is still a common treatment for SLE patients [32]. Saghiri R and colleagues have showed the elevated serum tADA and ADA2 activity in SLE patients compared with

ADA activity in rheumatoid arthritis

rheumatoid arthritis (RA) is a common chronic autoimmune disease with unknown etiology, which is characterized by joint destruction and inflammatory synovitis. The changes of ADA activity in RA patients were inconsistent from different studies (Table 2). Several studies have showed that ADA were increased in RA patients, while ours study showed that tADA, ADA1 and ADA2 activities were all not different between RA patients and age & sex matched healthy controls [38]. In addition, the reports of

ADA activity in juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) covers a heterogeneous group of connective tissue diseases which are similar in onset which is before the age of 16 and that they last for at least 6 weeks. According to the clinical feature, JIA patients were categorized into these subtypes: systemic JIA (sJIA), oligoarthritis, ployarthritis, enthesitis Related JIA (ERA), psoriatic JIA and undefined JIA. There were few studies about the ADA activity in JIA patients. Hitoglou S and colleagues showed that

ADA activity in AILD

AILD constitutes a group of chronic inflammatory diseases with unknown etiology and pathophysiology, and characterized by hyperglobulinemia, presence of auto-antibodies, and inflammation within the liver. Primary Biliary Cirrhosis (PBC), Autoimmune Hepatitis (AIH), and Primary Sclerosing Cholangitis (PSC) are the classic types of AILD. Torgutalp M and colleagues have showed that ADA activity were significantly higher and was correlated with inflammatory activity in AIH patients [25]. In our

ADA activity in Adult-Onset Still's Disease

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with unknown etiology, characterized by fever, rash, arthritis, and neutrophilic leucocytosis, etc. There are no specific diagnostic indexes for AOSD. Pubmed were searched using the terms “ADA, adult-onset Still's disease”. Only one report in 2013 by Xun C and colleagues studied the potential role of ADA activity in AOSD diagnosis. Theirs study showed that ADA activity was higher in AOSD patients than that in SLE and healthy

Systemic sclerosis

Systemic sclerosis (SSc) is a rare chronic systemic autoimmune disease of unknown etiology, characterized by vascular abnormalities and fibrosis involving the skin and internal organs, such as the gastrointestinal tract, lung, heart and kidneys. Sasaki T showed that serum ADA activity was increased in patients with progressive systemic sclerosis (PSS) [42]. And furthermore, Meunier P and colleagues found that plasma ADA activity were higher in patients with PSS involvement of the skin and other

ADA activity in autoimmune diseases of the nervous system

It is well known that ADA activity is increased in CSF of patients with tubercular meningitis (TBM) and has been used for differential diagnosis of TBM. In this paper, we analyzed the literatures to reveal that whether the ADA activity was changed in autoimmune diseases of the nervous system.

Summary

In summary, ADA activity are increased in several types of autoimmune disease. The measure of ADA activity would be helpful in clinical diagnosis or disease activity monitoring.

Funding

This work is supported by the Basic Research Program of Natural Science of Shaanxi Province (2020JM-315).

Declaration of Competing Interest

The authors declare that they have no conflict of interest.

References (51)

  • M. Samuraki et al.

    Multiple sclerosis showing elevation of adenosine deaminase levels in the cerebrospinal fluid

    Mult Scler Relat Disord

    (2017)
  • S. Chiba et al.

    High serum adenosine deaminase activity and its correlation with lymphocyte subsets in myasthenia gravis

    J Neurol Sci

    (1990)
  • W.T. Ma et al.

    The role of monocytes and macrophages in autoimmune diseases: a comprehensive review

    Front Immunol

    (2019)
  • E. Meffre et al.

    Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies

    Immunol Rev

    (2019)
  • E.K. Kapsogeorgou et al.

    Autoantibodies in autoimmune diseases: clinical and critical evaluation

    Isr Med Assoc J

    (2016)
  • K.V. Whitmore et al.

    Adenosine deaminase deficiency - more than just an immunodeficiency

    Front Immunol

    (2016)
  • L. Antonioli et al.

    Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders

    Curr Drug Targets

    (2012)
  • A. Aiuti et al.

    Gene therapy for adenosine deaminase deficiency

    Curr Opin Allergy Clin Immunol

    (2003)
  • A. Aiuti et al.

    Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products

    EMBO Mol Med

    (2017)
  • A. Habib et al.

    Diagnostic accuracy of cerebrospinal fluid adenosine deaminase in detecting tuberculous meningitis

    Pak J Med Sci

    (2018)
  • H.B. Xu et al.

    Diagnostic value of adenosine deaminase in cerebrospinal fluid for tuberculous meningitis: a meta-analysis

    Int J Tuberc Lung Dis

    (2010)
  • R.M. Terra et al.

    Pleural fluid adenosine deaminase (ADA) predicts survival in patients with malignant pleural effusion

    Lung.

    (2016)
  • H. Yildirim et al.

    Increased pleural fluid adenosine deaminase levels in patients with malignant pleural effusions: a potential predictor of talc pleurodesis outcome

    Lung.

    (2007)
  • A.N. Aggarwal et al.

    Adenosine deaminase for diagnosis of tuberculous pleural effusion: a systematic review and meta-analysis

    PLoS One

    (2019)
  • X. Lei et al.

    Diagnostic value of pleural effusion mononuclear cells count and adenosine deaminase for tuberculous pleurisy patients in china: a case-control study

    Front Med (Lausanne)

    (2019)
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