Background/Purpose: To evaluate the clinical effectiveness of IFI44L gene methylation detection for the diagnosis of Systemic Lupus Erythematosus (SLE) by MS-HRM, to determine  the relative risk (RR) in early suspected cases which were positive and negative respectively with IFI44L gene methylation detection and the relationship between the IFI44L gene biomarker and early onset of SLE.

Methods: In this clinical trial, Methylation Sensitive High Resolution Melting (MS-HRM) method was employed for detecting IFI44L gene methylation level of 1126 peripheral blood mononuclear cell (PBMC) samples in SLE patients and nonSLE patients with other autoimmun diseases ( Adult onset stills disease (AOSD), Rheumataoid arthritis (RA), dermatomyositis (DM) , primary sjogren’s syndrome (pSS),mixed connective tissue disease (MCTD)).  Synchronous blind comparison were conducted  with the 2012 SLICC criteria and suspected cases were followed-up for 6 months till the onset of SLE and clinical diagnostical confirmation.

Results: 1. The relative risk (RR) of early suspected cases was RR=17.06 ,which is RR >10, indicating that hypomethylation in the promoter region of IFI44L gene was strongly  associated with the development of SLE disease (n=576).

2. The results of IFI44L gene methylation levels were in good agreement with the 2012 SLICC criteria,and the sensitivity ,specificty and total coincidence were 90.53%，92.52% and 91.47% respectively.

3. The IFI44L gene biaomarker (Kappa index 0.8166) was significantly better than anti-nuclear antibody,anti-Sm antibody and anti-dsDNA antibody (Kappa index 0.2-0.5)when respectively campared with the clinical 2012 SLICC criteria.

4. The comparasion of IFI44L gene biomarker and the pyrosequencing was also in good relationship with a Kappa index of 0.8606.

Conclusion: The hypomethylation of IFI44L gene promoter region measured by MS-HRM is strongly associated with the occurrence and development of SLE disease, and is not associated with other autoimmun diseases (AOSD,RA,pSS and MTCD) ,which can be used for early diagnosis of SLE onset. The detection results were compared with the results of the the 2012 SLICC criteria and had high positive, negative,and total coincidence, and significantly superior to the three autoantibodies mentioned above.The IFI44L gene biaomarker is a promising and practical laboratory method for clinical use for SLE early diagnosis and treatment.

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-evaluation-on-ifi44l-gene-methylation-detection-for-diagnosis-of-systemic-lupus-erythematosus-by-methylation-sensitive-high-resolution-melting-ms-hrm/