TITLE: Protocol: HLA-DQB1*0301, HLA-DQB1*0501, and HLA-DQA1*0301 and Their Role in Scleroderma- A Systematic Review 
AUTHORS: Dylan  Thibaut, Jared  Lehman, Alexis  Marquess, Kersten  Schroeder

[DESCRIPTION]
Scleroderma remains a debilitating autoimmune condition with immunological linkage to HLA sequences remaining open for further explanation. Through understanding the linkage of specific HLAs to scleroderma, the immunological processes behind the condition can be elucidated. HLA meta-analysis with scleroderma offers a prognostic application to best interpret the odds of scleroderma given a specific HLA. We hope to conduct a meta-analysis to determine how HLA-DQB1*0301, HLA-DQB1*0501, and HLA-DQA1*0301 are linked with scleroderma.

[STEPS]
SECTION: Administrative Information
1. Title
Protocol: HLA-DQB1*0301, HLA-DQB1*0501, and HLA-DQA1*0301 and Their Role in Scleroderma- A Systematic Review 
SECTION: Administrative Information
2. Registration
Registration is via protocols.io
SECTION: Administrative Information
3. Authors

Dylan Thibaut: Lake Erie College of Osteopathic Medicine - Bradenton, AdventHealth- Sebring, University of Central Florida
ORCID: https://orcid.org/0000-0002-8739-9688

Jared Lehman: Lake Erie College of Osteopathic Medicine - Bradenton, AdventHealth- Sebring
ORCID:  https://orcid.org/0000-0001-7524-9175

Alexis Marquess: Lake Erie College of Osteopathic Medicine - Bradenton
ORCID: https://orcid.org/0000-0001-6799-9072

Principle Investigator
Dr. Kersten T Schroeder, PhD: University of Central Florida
ORCID: https://orcid.org/0000-0002-8412-323X


SECTION: Administrative Information
4. Amendments
None
SECTION: Administrative Information
5. Support

Sources: No financial sources used
Sponsor: Lake Erie College of Osteopathic Medicine- Bradenton
Role of Sponsor: to facilitate ethical research and oversee the research process from start to end
SECTION: Introduction
6. Rationale
Scleroderma remains a debilitating autoimmune condition with immunological linkage to HLA sequences remaining open for further explanation. Through understanding the linkage of specific HLAs to scleroderma, the immunological processes behind the condition can be elucidated. In addition, HLA meta-analysis with scleroderma offers a prognostic application to best interpret the odds of scleroderma given a specific HLA.
SECTION: Introduction
7. Objectives
We hope to conduct a meta-analysis to determine how HLA-DQB1*0301, HLA-DQB1*0501, and HLA-DQA1*0301 are linked with scleroderma.
SECTION: Methods
8. Eligibility criteria
Only studies between 1995 and 2022 are included.
SECTION: Methods
9. Information sources
Google Scholar and Pubmed will be accessed during the duration of the study to gather data.
SECTION: Methods
10. Study records
SECTION: Data Synthesis
14. 15a: Data will be examined using Revman 5.4 and/or MetaXL as needed.

SECTION: Methods
10.1. Data management
Data will be collected by two researchers and will be compiled on a document. 
SECTION: Methods
10.2. Selection process
To be included, articles must: contain odds ratio (or enough data to calculate it), be in English, and must use living human test subjects. 
 Inadequate information for meta-analysis, studies with flawed design, or meta-analyses on the same HLAs are not included. 
SECTION: Methods
10.3. Data collection process
Two researchers will individually find and compare studies for inclusion. If in disagreement, researchers will present the study to the PI for the PI to make the final decision on whether to include the information.
SECTION: Methods
11. Data Items
Data collected will include case numbers, control numbers, associated p values if available, the samples studied, odds ratios, confidence intervals, and the name as well as year of the study examined.
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12. Outcomes and prioritization
HLA-DQB1*0301, HLA-DQB1*0501, and HLA-DQA1*0301 will specifically be examined.
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13. Risk of bias in individual studies
The NIH Quality Assessment of case-control studies tool will be used for risk of bias assessment as well as a generated DOI plot.
SECTION: Data Synthesis
15. 15b: I^2 will be used as a method of examining heterogeneity.

SECTION: Data Synthesis
16. 15c: MetaXL or Revman 5.4 are used if needed for sensitivity analysis.

SECTION: Data Synthesis
17. 15d: Quantitative synthesis is appropriate.
SECTION: Meta-bias and Confidence
18. Meta-bias and confidence in cumulative evidence
GRADE criteria will be used.

19.