IFI44 identified as a novel biomarker for primary Sjögren’s syndrome

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Primary Sjögren’s syndrome (pSS), characterized by lymphocyte infiltration into exocrine glands, poses significant challenges due to its heterogeneous presentation and overlap with other autoimmune diseases. Now, a recent study published in the Journal of Inflammation Research highlighted Interferon induced protein 44 (IFI44) as a novel and reliable biomarker for pSS, offering new avenues for accurate diagnosis and targeted treatment strategies. 

The study conducted by Chinese researchers from Tianjin University analyzed gene expression profiles from the Gene Expression Omnibus (GEO) database using advanced statistical methods. They identified differentially expressed genes, highlighting IFI44 as a key candidate. Further analysis demonstrated that IFI44 exhibited a strong negative correlation with resting natural killer (NK) cells, macrophages M0, and eosinophils, while showing a positive correlation with activated dendritic cells, naive B cells, and activated CD4 memory T cells. Additionally, IFI44 was strongly linked to clinical traits, including IgG, SSA, SSB, ANA, and ESSDAI, solidifying its potential as a biomarker. The researchers also investigated the competitive endogenous RNA (ceRNA) network regulated by IFI44, identifying hsa-miR-944, hsa-miR-9-5p, hsa-miR-126-5p, and hsa-miR-335-3p as pivotal regulators, further emphasizing its diagnostic relevance. 

IFI44 is a cytoplasmic protein with a guanosine-5′-triphosphate (GTP)-binding domain, playing a pivotal role in immune responses to autoimmune diseases. Despite containing a GTP-binding domain, IFI44 shares no structural homology with GTPases or G proteins. This unique protein is known to induce an antiproliferative state in cells, highlighting its potential regulatory role in cellular defense mechanisms. IFI44 was first identified as a hepatitis C virus (HCV)-associated microtubular aggregate protein, isolated from the hepatocytes of HCV-infected chimpanzees. It is classified as an interferon-stimulated gene (ISG), with its expression upregulated following infections by various viruses, including rhinovirus. A study by Zheng et al. identified IFI44 as a common biomarker and therapeutic target for rheumatoid arthritis (RA), COVID-19, and Staphylococcus aureus bacteremia (SAB). The research revealed that IFI44 plays a critical role in modulating the immune response by negatively regulating the interferon (IFN) signaling pathway, which facilitates viral replication and bacterial proliferation. 

Identifying IFI44 as a novel biomarker could significantly improve the diagnosis and management of pSS. The findings hold immense promise for the rheumatology community, offering a new avenue for early detection, targeted treatment, and improved patient outcomes. 

References  

  1. Wei B, Yue Q, Ka Y, Sun C, Zhao Y, Ning X, Jin Y, Gao J, Wu Y, Liu W. Identification and Validation of IFI44 as a Novel Biomarker for Primary Sjögren’s Syndrome. J Inflamm Res. 2024 Aug 28;17:5723-5740. 
  2. DeDiego ML, Nogales A, Martinez-Sobrido L, Topham DJ. Interferon-Induced Protein 44 Interacts with Cellular FK506-Binding Protein 5, Negatively Regulates Host Antiviral Responses, and Supports Virus Replication. mBio. 2019 Aug 27;10(4):e01839-19.  
  3. Pan H, Wang X, Huang W, Dai Y, Yang M, Liang H, Wu X, Zhang L, Huang W, Yuan L, Wu Y, Wang Y, Liao L, Huang J, Guan J. Interferon-Induced Protein 44 Correlated With Immune Infiltration Serves as a Potential Prognostic Indicator in Head and Neck Squamous Cell Carcinoma. Front Oncol. 2020 Oct 6;10:557157. 
  4. Zheng Q, Wang D, Lin R, Lv Q, Wang W. IFI44 is an immune evasion biomarker for SARS-CoV-2 and Staphylococcus aureus infection in patients with RA. Front Immunol. 2022 Sep 15;13:1013322.