Comparison of rheumatoid arthritis factors, adenosine deaminases and uric acid in arthritis and non-arthritis patients: A protocol

Priyanka A. Makhe; Anjali Vagga; Archana Dhok

doi:10.12688/f1000research.139085.1

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Study Protocol

Comparison of rheumatoid arthritis factors, adenosine deaminases and uric acid in arthritis and non-arthritis patients: A protocol

[version 1; peer review: 1 approved, 1 approved with reservations]

Priyanka A. Makhe ¹, Anjali Vagga^1,2, Archana Dhok²

PUBLISHED 25 Sep 2023

Author details Author details

¹ Biochemistry, Datta Meghe Institute of Higher Education Research, wardha, Maharastra, 442001, India
² Biochemistry, Datta Meghe Institute Higher Education Research, Wardha, Maharastra, 442001, India

Priyanka A. Makhe
Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing

Anjali Vagga
Roles: Conceptualization, Supervision, Validation, Visualization

Archana Dhok
Roles: Conceptualization, Investigation, Supervision, Validation

OPEN PEER REVIEW

REVIEWER STATUS

This article is included in the Datta Meghe Institute of Higher Education and Research collection.

Abstract

Rheumatic disorders are viewed as a public health issue because they affect thousands of individuals around the world and increase health care expenses. Numerous biochemical markers may play a role in the pathophysiology and etiology of rheumatoid arthritis (RA) due to its local as well as systemic inflammatory effects. Rheumatoid factors (RF) can be found in a variety of people, including young, healthy people, the elderly, and people with RA. In this study we will assess and compare the occurrence, clinical presentation, effects and possible risk of biochemical parameters such as uric acid, adenosine deaminase (ADA,), RA factor between arthritis patients and non - arthritis patients. A total of 82 participants — 41 RA patients and 41 healthy controls (non-arthritis patients) —will be included in the study. The levels of serum ADA, uric acid, and rheumatoid factor will be examined, and independent tests will be used for the statistical analysis. Serum ADA rheumatoid factors levels in RA patients is higher in healthy control. When comparing the uric acid levels of RA patients with healthy controls, there is no significant change in the uric acid level. The degree underlying ADA activity between RA patients and healthy individuals should differ noticeably, confirming the test’s value in the diagnosis of the condition.

Keywords

Uric Acid, Adenosine Deaminases, Ra Factor, Rheumatoid Arthritis, Non-Arthritis Patients, Biochemical Parameters, Healthy Control, Antibodies.

Corresponding author: Priyanka A. Makhe

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2023 Makhe PA et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Makhe PA, Vagga A and Dhok A. Comparison of rheumatoid arthritis factors, adenosine deaminases and uric acid in arthritis and non-arthritis patients: A protocol [version 1; peer review: 1 approved, 1 approved with reservations]. F1000Research 2023, 12:1202 (https://doi.org/10.12688/f1000research.139085.1) First published: 25 Sep 2023, 12:1202 (https://doi.org/10.12688/f1000research.139085.1) Latest published: 25 Sep 2023, 12:1202 (https://doi.org/10.12688/f1000research.139085.1)

Introduction

Targeting the Fc region, which is a part of immunoglobulin G, are antibodies with various isotypes and affinities that are referred to as rheumatoid factors. As mentioned in the literature, since the first discovery of rheumatoid factors 80 years ago, the identification of both anticitrullinated protein antibody and anti-carbamylated protein antibodies has greatly facilitated approaches for early diagnosis of RA.¹ Patients started exhibiting signs of rheumatoid arthritis before 70 years ago.¹

An antibody described by Waaler in 1940 boosted the agglutination of sheep red blood cells when subagglutinating doses of rabbit antibodies were used. Meyer first identified serum gamma-globulins as a target of these antibodies in 1922 in Ref. 2 patients with chronic bronchitis and liver cirrhosis. In 1948, Rose became the first to describe these antibodies among rheumatoid arthritis patients.³ They were finally given the name “rheumatoid factors” in 1952 because of their link to rheumatoid arthritis (RA).⁴ Adenosine deaminase (ADA) breaks down adenosine. ADA has been proposed as a helpful indicator⁵ to assist in the diagnosis, prognosis, as well as therapy assessment of RA.⁶ It is recognised as a reliable sign of cell-mediated immunity. ADA activity is increased in rheumatoid arthritis patients.⁷

Adenosine deaminase is an enzyme that promotes the unchangeable hydrolytic deamination of adenosine to inosine and 2′-deoxyadenosine to 2′-deoxyinosine in red blood cells and the arterial wall. Hypoxanthine, xanthine, and then uric acid (UA) are produced from inosine and 2′-deoxyinosine.⁸ In humans, both endogenous as well as dietary purine metabolism produce UA.⁹ The substantial correlation between the level of blood including interleukin-6 (IL-6), C-reactivity protein (CRP), tumour necrosis factor (TNF) and serum UA raises the possibility that UA plays a significant role in systemic inflammation in inflammatory-related diseases, including RA.¹⁰

The oxidant-antioxidant status of RA patients can be assessed by measuring their serum UA and ADA.

Patients with a variety of nonrheumatic arthritic disorders can have RFs. The majority of the time, CD5-positive B cells naturally generate polyreactive, low-affinity IgM antibodies as RFs.¹¹^,¹² RFs are detectable in 40–50% of hepatitis C virus-infected patients, while their frequency might reach 76%.¹³

RA constitutes a symmetrical, chronic, inflammatory autoimmune disease which initially affects cartilage and joints as well as the eyes, skin, heart, kidneys, and lungs. Inflammation (painful swelling) takes place in the affected body parts as a result of the body’s immune system mistakenly attacking healthy cells in the body.¹⁴

Joint destruction is frequently a gradual result of synovial inflammation and degradation.¹⁵ The most prevalent autoimmune systemic illness in the world is RA.¹⁶ In the general population, RA affects 1-2% of people.¹⁷ Approximately 70% patients have irreparable joint injury, and 80% of active young individuals in the workforce suffer from stiffness and agonising pain.¹⁸ Approximately 0.5–1% of people worldwide have RA¹⁹ and 1% worldwide.²⁰

RA affects around 10 million people in India alone.²¹ Women are far more likely than men to develop RA between the ages of 40 and 60.²² RA patients are 1.5–2 times more likely to develop cardiovascular disease (CVD) than persons without the condition who are the same age and sex.²³

Objectives

To assess the occurrence, prevalence, clinical presentation and possible risk factors of UA, ADA, RA factor in arthritis and non-arthritis patients.

• To measure the prevalence of ADA in people with RA.
• To measure the prevalence of UA in people with RA.
• To calculate the prevalence of RA factors in people with RA.
• To calculate the prevalence of RA factors in patients without RA.
• To calculate the prevalence of ADA in patients without RA.
• To calculate the concentration of UA in patients without RA.

Protocol

The study will be conducted among the common population of the Vidarbha district in AVBRH hospital. Between RA patients and their healthy controls, there should be significant variations in the levels of the ADA RA factor as well as the activity of UA, which may suggest the test’s effectiveness in RA diagnosis.

Material and methods

The following study will be started in collaboration on behalf of Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi (Meghe), Wardha, in the Biochemistry division of the Department of Biochemistry, Jawaharlal Nehru Medical College (JNMC), Sawangi (Meghe), conduct the study between October 2022-2024. A total of 41 RA patients will be enrolled as cases and 41 healthy patients will be enrolled as controls. Only patients between the ages of 30 and 60 will be chosen for this study. Before and throughout the trial, all ethical procedures will be followed and written consent form will be obtained at the time of sample collection. Patients with RA factor positivity will be considered for the trial. Patients with primary inflammatory joint illness, either currently or in the past, septic arthritis in a native joint, malignancy, demyelinating disease, soft tissue swelling, rheumatoid nodules, osteopenia in hand/wrist joints, radiographic erosive changes, and gout will be excluded from the study.

Sample collection

For collection of blood sample, the right arm’s antecubital site will be mostly selected. To puncture the site, a tourniquet, cotton, syringe, and rubbing alcohol will be needed. We will be applying the tourniquet about 3-4’ above the venipuncture site, after which we will clean the area by using a cotton and alcohol, and then the needle will be insert. According to requirements, samples will be collected in a plain vial (up to 5 mL). After collection of the sample, the tourniquet will be removed and cotton will be apply to prevent bleeding. Then the vial will be labelled with the patient’s name and required test name. After labelling, the sample will be sent to the biochemistry processing lab. In the lab, to process the sample, first the serum will be separated by using a REMI R-8C Plus centrifuge at 3000rpm for 5-7 min. Then the level of UA, ADA, RA (required test) will be measured by using a Vitros 5600 Dry Chemistry Analyzer Machine manufactured by Ortho Clinical Diagnostics.

After centrifuge, the serum levels of UA, ADA, and RA factors will be measured using a Vitros 5600 Dry Chemistry Analyzer Machine manufactured by Ortho Clinical Diagnostics.

1. For statistical analysis, SPSS software for windows version 27.0 will be used.

Statical significance will be defined at p<0.001.

Study design

This study will be cross-analytical.

Study settings

The study will be conducted at Aacharya Vinoba Bhave Rural Hospital Sawangi (Meghe), Wardha.

Inclusion criteria

This research will include a total of 82 patients between 30-60 years old.

Subjects of both sexes will be included.

Exclusion criteria

The study will exclude patients experiencing swelling, rheumatoid nodules, osteopenia in hand/wrist joints, radiographic erosive changes, gout.

Bias

All necessary measures to control bias at all levels will be taken by using random sampling.

Sample size

Formula for sample size estimation:

n \geq {(\frac{z_{1 - \frac{α}{2} σ}}{d})}^{2}

n \geq {(\frac{z_{1 - \frac{0.5}{2} 14.6}}{3.17})}^{2}

n = 82

A total of 82 participants will be needed in the study, in which 41 will be patients and 41 will be healthy controls.

The data analysis will be done using relevant Chi-squared test for understanding the comparative difference between groups and among groups, whereas the results obtained during the research will be analyzed [using appropriate statistical method by a qualified statistician]. All the response will be calculated using software version 4.3.

All the results for the outcome variables will be presented in tables and will be described over descriptive statistics. Outcome variables (RA factor [IU/mL], ADA [U/L] and UA [mg/dL]) will first be tested for normality for the quantitative measurement of mean and standard deviation (SD). Positional average (median) statistics will be used to look for skewed distributions and calculating the interquartile range (IQR). All the binary and categorical variables will be described over the frequency and percentages for qualitative assessment. Results will be calculated using R software free version 4.3.2 for all statistical analyses.

The inferential statistics for testing the significant difference over the outcome variables will be evaluated at 5% level of significance (p ≤ 0.05). If data for the outcome variable shows a non-normal distribution for the quantitative assessment, it will be converted for normal distribution following mathematical algorithm. If data persist with a non-normal distribution we will use alternative non-parametric tests (Chi-square, Mann-Whitney U, Wilcoxon tests). Outcome variables like RA factor (IU/mL), ADA (U/L) and UA (mg/dL) will be subjected to a t-test (independent) to find the significance of the mean.

Study status

The study currently ongoing with sample collection and is expected to be completed before October 2024.

Expected outcomes

A normal rheumatoid factor value may be less than 15 IU/mL, and one over 100 IU/mL is strongly associated with autoimmune diseases like RA. All RA patients should have their serum ADA levels (IU/L) checked, and these levels should be significantly greater in RA patients. In RA patients as well as healthy controls, UA levels may or may not vary significantly.

Discussion

Rheumatoid arthritis (RA) is a complex illness that affects many body tissues and the immune system. Overall, 80% of RA patients experience the initial symptoms and signs of the disease between the ages of 30 and 60, and females are likely to be affected by it two times more frequently than males. T cells may localise and increase the effector activities of monocyte/macrophages in rheumatoid illness, according to the predominance among T cells as well as monocyte/macrophages in rheumatoid synovium.²⁴^,²⁵

Neha Singh and co-workers (2021) aimed to evaluate patient education regarding rheumatoid arthritis. They found that the severity of RA, a chronic, inflammatory, and systemically autoimmune disease, on a patient” joints varies. Sex, age, genetics, environmental factors (tobacco use, exposure to air pollution, and occupational hazards) are risk factors. If left untreated, Felty syndrome can develop into a variety of consequences, including rheumatoid vasculitis, persistent joint damage needing arthroplasty, and Felty syndrome necessitating splenectomy. The objectives of treatment for RA are to alleviate discomfort and prevent/slow additional damage because there is no known cure. Here, we give a succinct overview of the numerous previous and present therapy options for RA problems.¹⁴

Zahra Zakeri et al. (2012) discovered that patients with osteoarthritis and RA differed in their serum as well as synovial fluid levels of ADA. It is crucial to ascertain the degree of inflammation and the response to treatment because of the chronic nature of RA, the disease’s poorly understood pathophysiology, and the disabling character of the condition. Therefore, the ability of the synovial fluid ADA to diagnose RA was assessed in this study as a result of non-specific clinical characteristics and a lack of diagnostic assays.²⁶

According to Zamani et al., there is a correlation between the ADA and disease activity, and blood ADA levels may aid in predicting activity of the disease in RA patients.²⁷

According to Nalesnik et al., ADA activation is directly linked to inflammation, and it may be an effective biochemical measure of the inflammatory process in people with RA.²⁸

Chanchal Garg et al. (2019) observed the CRP, UA and ADA levels in patients with RA. Synovial membrane inflammation is a hallmark of RA, while a state of oxidative stress is frequently linked to tissue damage. UA and inflammation are both significantly influenced by ADA, an endogenous antioxidant with the ability to scavenge free radicals. According to the study’s findings, RA patients had considerably higher serum levels of ADA, CRP, and rheumatoid factor as compared to controls.²⁹ This studyalso assessed how much UA is present. UA acts as a protective antioxidant that is especially good at binding hydroxyl, superoxide, and peroxinitrite radicals, which helps to avoid lipid peroxidation. There was no discernible difference in the levels of UA between RA patients and healthy participants. The study exhibited normal UA levels; however, this may be due to raised utilisation of UA in capturing free radicals and converting them to allantoin. An increase in UA levels due to enhanced ADA levels among RA patients is expected.²⁷^,³⁰^,³¹

Implication of the study

People all throughout the world are afflicted by RA. There are around 10 million RA sufferers in India. Over 70% of those who have rheumatoid arthritis and experience exhaustion on a daily basis and have symptoms of chronic fatigue syndrome.

High-affinity RFs are associated with more severe and long-lasting illness in RA patients, and low-affinity RFs have been shown to be important players in immunological responses to numerous pathogens.

The determination of RA and its consequences, which are brought on by the presence of UA and ADA among rheumatoid arthritis patients, were the main focus of this study. It has been discovered that ADA levels are elevated in RA patients, indicating the value of ADA in illness detection. The extracellular release of ADA during RA inflammation causes cell-mediated immunity to significantly boost its activity. It suggests that while UA may be considered a marker for the diagnosis of RA patients, it is not a meaningful signal in these individuals. In RA patients, UA levels are a significant predictor of renal impairment. Patients with increased UA who have RA may need to be screened for renal failure and given the proper care. According to one study, women who self-reported having RA had noticeably higher serum UA levels. Gout can be brought on by too much of this metabolic waste product in the blood. It results from increasing and crystallising urate. Joints could then become clogged with these crystals, which would hurt and inflame them.³²

By conducting this study, we will be able to carry out early assessment of RA patients with their consent. This study will be helpful for prevention of autoimmune diseases like RA which causes high levels of UA and ADA in patients.

Study limitations

Our study has a smaller sample size.

Data availability

No data are associated with this article.

Ethical considerations

This study was approved by the Datta Meghe Institute of Higher Education Institutional Ethics Committee (DMIHER (DU)/IEC/2023/599).

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Author details Author details

¹ Biochemistry, Datta Meghe Institute of Higher Education Research, wardha, Maharastra, 442001, India
² Biochemistry, Datta Meghe Institute Higher Education Research, Wardha, Maharastra, 442001, India

Priyanka A. Makhe
Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing

Anjali Vagga
Roles: Conceptualization, Supervision, Validation, Visualization

Archana Dhok
Roles: Conceptualization, Investigation, Supervision, Validation

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

Article Versions (1)

version 1

Published: 25 Sep 2023, 12:1202

https://doi.org/10.12688/f1000research.139085.1

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© 2023 Makhe PA et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Makhe PA, Vagga A and Dhok A. Comparison of rheumatoid arthritis factors, adenosine deaminases and uric acid in arthritis and non-arthritis patients: A protocol [version 1; peer review: 1 approved, 1 approved with reservations]. F1000Research 2023, 12:1202 (https://doi.org/10.12688/f1000research.139085.1)

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Reviewer Report 10 Sep 2024

Marta Benito-Miguel, Health Sciences Department, Comillas Pontifical University San Juan de Dios School of Nursing and Physiotherapy, San Rafael, Comunidad de Madrid, Spain

Approved

https://doi.org/10.5256/f1000research.152330.r290130

This article is a protocol and has no data. It addresses an important topic because rheumatic disorders affect thousands of individuals around the world.

Despite the protocol is very simple, they are only 2 variables to evaluate, ... Continue reading

This article is a protocol and has no data. It addresses an important topic because rheumatic disorders affect thousands of individuals around the world.

Despite the protocol is very simple, they are only 2 variables to evaluate, but if there is a correlation, it should make an important contribution to be a simple evaluation method to add to detect rheumatoid arthritis.

Is the rationale for, and objectives of, the study clearly described?

Yes
Is the study design appropriate for the research question?

Yes
Are sufficient details of the methods provided to allow replication by others?

Yes
Are the datasets clearly presented in a useable and accessible format?

Not applicable

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Rheumatoid Arthritis

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

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Reviewer Report 27 Oct 2023

Bogdan Cylwik, Department of Pediatric Laboratory Diagnostics, Medical University of Bialystok, Bialystok, Poland

Approved with Reservations

https://doi.org/10.5256/f1000research.152330.r210010

The study protocol article of Priyanka Makhe et al. evaluates the diagnostic usefulness of serum rheumatoid factor (RF), uric acid (UA) levels and adenosine deaminase activity in rheumatoid arthritis (RA) patients. In short, this is an interesting project and research ... Continue reading

The study protocol article of Priyanka Makhe et al. evaluates the diagnostic usefulness of serum rheumatoid factor (RF), uric acid (UA) levels and adenosine deaminase activity in rheumatoid arthritis (RA) patients. In short, this is an interesting project and research idea, however, the authors should better explain its purpose. The authors need to explain why ADA activity determination in RA would be so important. Finally, the authors stated that ADA could be a promising test for the diagnosis of RA patients. I have a few comments and suggestions to the authors.

The following points need improvement:

Abstract:

Is: “Rheumatoid factors (RF)”. Should be: “Rheumatoid factor(RF)”.

Is: “The levels of serum ADA….”. Should be: “The serum ADA activity…”.

Is: “ Serum ADA rheumatoid factors levels in RA patients is higher in healthy control” (?).

Should be: “Serum ADA activity in RA patients is higher than that in controls”.

Is: “When comparing the uric acid levels of RA patients with healthy controls, there is no change in the uric acid level”. Maybe: “When comparing the uric acid levels between RA patients and controls, there is no significant difference”.

Is: “The degree underlying ADA activity between RA patients and healthy individuals should differ noticeably, confirming the test's value in the diagnosis of the condition”. Maybe more precisely: “The ADA activity between RA patients and healthy individuals should differ noticeably, confirming the usefulness of the test in the diagnosis of the condition”.

Keywords:

Is: “Ra Factor”. Should be: “Rheumatoid Factor”.

Introduction:

Is: “C-reactivity protein”. Should be: “C-reactive protein”.

Objective:

The goals are not clear and poorly written. Rather should be:

To determine the serum ADA activity in RA patients

To determine the serum UA level in RA patients

To determine the serum RF level in RA patients

To determine the serum ADA activity, UA and RF concentrations in patients without RA

Protocol:

The purpose of the research should be clarified. The sentence “Between RA patients and their healthy controls, there should be significant variations in the levels of ADA RA factor…” needs to be corrected.

Material and methods:

The study group collected over a 3-year period appears to be small. Diagnostic criteria for RA should be provided. Exclusion criteria are unclear.
Control group - it should be specified whether these will be healthy people or hospitalized patients. I don't understand what "healthy patients" means.

Sample collection: too detailed description.

Methods: there are no principles of the methods for determining uric acid, rheumatoid factor and ADA.

Statistical analysis:

What will the Wilcoxon test be used for?

What p-value will be considered statistically significant (p<0.001 or p<0.05)?

Why will research results be processed by 3 different software versions?

Is the rationale for, and objectives of, the study clearly described?

Partly
Is the study design appropriate for the research question?

Yes
Are sufficient details of the methods provided to allow replication by others?

No
Are the datasets clearly presented in a useable and accessible format?

Not applicable

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Rheumatic diseases

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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Bogdan Cylwik, Medical University of Bialystok, Bialystok, Poland
Marta Benito-Miguel, Comillas Pontifical University San Juan de Dios School of Nursing and Physiotherapy, San Rafael, Spain

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Reviewer Report

3 Views

10 Sep 2024 | for Version 1

Marta Benito-Miguel, Health Sciences Department, Comillas Pontifical University San Juan de Dios School of Nursing and Physiotherapy, San Rafael, Comunidad de Madrid, Spain

3 Views Cite this report Responses(0)

Approved

This article is a protocol and has no data. It addresses an important topic because rheumatic disorders affect thousands of individuals around the world.

Despite the protocol is very simple, they are only 2 variables to evaluate, but if there is a correlation, it should make an important contribution to be a simple evaluation method to add to detect rheumatoid arthritis.

Is the rationale for, and objectives of, the study clearly described?

Yes
Is the study design appropriate for the research question?

Yes
Are sufficient details of the methods provided to allow replication by others?

Yes
Are the datasets clearly presented in a useable and accessible format?

Not applicable

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Rheumatoid Arthritis

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

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Reviewer Report

11 Views

27 Oct 2023 | for Version 1

Bogdan Cylwik, Department of Pediatric Laboratory Diagnostics, Medical University of Bialystok, Bialystok, Poland

11 Views Cite this report Responses(0)

Approved With Reservations

The study protocol article of Priyanka Makhe et al. evaluates the diagnostic usefulness of serum rheumatoid factor (RF), uric acid (UA) levels and adenosine deaminase activity in rheumatoid arthritis (RA) patients. In short, this is an interesting project and research idea, however, the authors should better explain its purpose. The authors need to explain why ADA activity determination in RA would be so important. Finally, the authors stated that ADA could be a promising test for the diagnosis of RA patients. I have a few comments and suggestions to the authors.

The following points need improvement:

Abstract:

Is: “Rheumatoid factors (RF)”. Should be: “Rheumatoid factor(RF)”.

Is: “The levels of serum ADA….”. Should be: “The serum ADA activity…”.

Is: “ Serum ADA rheumatoid factors levels in RA patients is higher in healthy control” (?).

Should be: “Serum ADA activity in RA patients is higher than that in controls”.

Is: “When comparing the uric acid levels of RA patients with healthy controls, there is no change in the uric acid level”. Maybe: “When comparing the uric acid levels between RA patients and controls, there is no significant difference”.

Is: “The degree underlying ADA activity between RA patients and healthy individuals should differ noticeably, confirming the test's value in the diagnosis of the condition”. Maybe more precisely: “The ADA activity between RA patients and healthy individuals should differ noticeably, confirming the usefulness of the test in the diagnosis of the condition”.

Keywords:

Is: “Ra Factor”. Should be: “Rheumatoid Factor”.

Introduction:

Is: “C-reactivity protein”. Should be: “C-reactive protein”.

Objective:

The goals are not clear and poorly written. Rather should be:

To determine the serum ADA activity in RA patients

To determine the serum UA level in RA patients

To determine the serum RF level in RA patients

To determine the serum ADA activity, UA and RF concentrations in patients without RA

Protocol:

The purpose of the research should be clarified. The sentence “Between RA patients and their healthy controls, there should be significant variations in the levels of ADA RA factor…” needs to be corrected.

Material and methods:

The study group collected over a 3-year period appears to be small. Diagnostic criteria for RA should be provided. Exclusion criteria are unclear.
Control group - it should be specified whether these will be healthy people or hospitalized patients. I don't understand what "healthy patients" means.

Sample collection: too detailed description.

Methods: there are no principles of the methods for determining uric acid, rheumatoid factor and ADA.

Statistical analysis:

What will the Wilcoxon test be used for?

What p-value will be considered statistically significant (p<0.001 or p<0.05)?

Why will research results be processed by 3 different software versions?

Is the rationale for, and objectives of, the study clearly described?

Partly
Is the study design appropriate for the research question?

Yes
Are sufficient details of the methods provided to allow replication by others?

No
Are the datasets clearly presented in a useable and accessible format?

Not applicable

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Rheumatic diseases

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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Comparison of rheumatoid arthritis factors, adenosine deaminases and uric acid in arthritis and non-arthritis patients: A protocol

Abstract

Keywords

Introduction

Objectives

Protocol

Material and methods

Sample collection

Study design

Study settings

Inclusion criteria

Exclusion criteria

Bias

Sample size

Study status

Expected outcomes

Discussion

Implication of the study

Study limitations

Data availability

Ethical considerations

References

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