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The interferon-induced protein 44-like gene (i.e., IFI44L gene) codes for the interferon-induced protein 44-like protein (i.e., IFI44L protein). This gene is located in band 1, region 1 (see band and gene nomenclature) on the short, i.e., "p", arm of chromosome 1 (location abbreviated as 1p31.1). A closely related gene, the interferon-induced protein 44 gene (i.e. the IFI44 gene), is a paralog of the IFI44L gene (i.e., the two genes are duplicates of an ancestorial gene).[1] The IFI44L and IFI44 proteins are composed of 452 and 444 amino acids, respectively, share 45% amino acid identity along with 60% homology at the amino acid level, and have many similar or overlapping functions and activities.[2][3] This article focuses on the function and clinical significance of the IFI44L gene and IFI44L protein.

The IFI444L gene is an interferon-stimulated gene in which type I interferons stimulate it to transcribe, i.e., make, its messenger RNA (mRNA) which in turn directs formation of the IFI44L protein.[2][4][5] Type I interferons are cytokines which immune cells secrete in response to the accumulation of cytoplasmic DNA that occurs in virus-infected cells, cancer cells, and cells with other abnormalities or injuries.[6][7] Humans have 13 different type I interferon-α proteins: type I interferon-α1, -α2, - α4, -α5, -α6, -α7, -α8, - α10, -α13, - α14, -α16, -α17, -α21, and 4 other type I interferon proteins, type I interferon-β, -ε, -κ, and -Ω.[8] These interferons bind to and stimulate the interferon-alpha/beta receptors located in a wide range of cells which when so stimulated act to promote or inhibit the inflammatory reactions associated with, e.g., certain infections, cancers, genetic disorders, cancers, and autoimmune diseases.[5][9][10][11][12] Among the many genes that they influence, type I interferons stimulate cells to transcribe the IFI44L gene (see interferon-alpha/beta signaling) thereby increasing production of the IFI44L protein.[5][10][13] Type I interferon-induced alterations in the IFI44L gene's expression can be helpful in diagnosing ,and in some cases may be potential targets for regulating the development and/or progression of, certain diseases.[14] Diseases caused and/or promoted by the type I interferons are termed interferon type I interferonopathies.[15]

n general, IFI44L has a significant involvement in malignant tumors. A huge number of genome sequencing studies have revealed that it is associated with the formation of tumors, can alter tumor growth and migration, and is associated with patient prognosis. The expression level of the IFI44L gene can be used to predict patient survival rates, and it has the potential to be a valuable diagnostic and prognostic marker.

Disorders associated with IFI44L gene abnormalities

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Viral infections

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Respiratory syncytial virus infections

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A 2016 study reviewing former publications on type I interferon-stimulated genes in lung infections caused by the respiratory syncytial virus (i.e., RSV) reported that the IFI44L gene was overexpressed in: a) the whole blood, oral mucosa, nasal mucosa, peripheral blood mononuclear cells (i.e., PBMCs), respiratory epithelium, and nasopharyngeal aspirates (i.e., suctions) in patients hospitalized for RSV-infections; b) the cord blood of RSV-infected newborn infants; c) several different human immortalized cell lines after being infected with RSV; and d) the lung tissue and blood of mice after being infected with RSV.[16] A subsequent study[12] found that: a) RSV stimulated cultured A549 cells (i.e., immortalized cells derived from human adenocarcinoma lung cells) to increase their IFI44L mRNA levels; b) intranasal injection of RSV into BALB/c mice increased the levels of IFI44L mRNA in their PBMCs; c) intranasal injection of RSV into C57BL/6N mice (i.e., mice that lack the IFI44L gene) developed greater weight losses and higher levels of RSV mRNA in their lung tissue than C57BL/6 mice (i.e., mice that have the IFI44L gene); d) cultured A549 cells that had their IFI44R gene disabled using gene knockout methods proliferated more rapidly than A549 cells that did not have this gene disabled; e) forced overexpression of the IFI44L gene in cultured 549 cells decreased their rate of proliferation; f) cultured A549 cells made to overexpress IFI44L mRNA had a lower percentage of cells that could be infected with RSV and a lower number of RSV recovered from their cultures; f) cultures of A549 cells made to express low levels of IFI44L mRNA and infected with RSV had 2-fold higher levels of RSV than cultures of RSV-infected cells that expressed normal levels of IFI44L mRNA; and g) following intranasal inoculation with RSV, C57BL/6N mice, which lack functional IFI44L and IIFI44 genes, developed a far more severe RSV infection that mice lacking only one of these genes. The study also reported that 12 infants with severe RSV infections who were admitted to a hospital had significantly lower levels of IFI44L and IFI44 mRNA in their PBMCs than 6 infants with mild RSV who were admitted to the same hospital.[12] This study concluded that: a) overexpression of the IFI44L gene reduces the growth of RSV and RSV-infected cells in cultured human lung cells and in mice; b) the increased expression of the IFI44L gene in infants infected with RSV is associated with significantly less severe disease than infants who expressed lower levels of the IFI44L gene; c) further studies are needed to confirm that overexpression of the IFI44L gene is associated with less severe RSV in infants infected with RSV, to determine if the IFI44L gene is overexpressed in children and adults with less severe RS, to determine if the levels of this gene's expression would be useful for predicting the severity of RSV infection, and if methods that promote overexpression of the IFI44L gene would be useful in treating RSV infections.[12][14]

Influenza A virus, coronavirus, lymphocytic choriomeningitis virus, and Covid19 infections

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In contrast to the findings in RSV infections, cultured A549 cells infected with the Influenza A virus or the lymphocytic choriomeningitis virus and cultured Huh7 human liver cancer cells infected with the human coronavirus 229E: a) had far higher IFI44L mRNA levels than mock-infected cells; b) had reduced numbers of these viruses in their respective cells when their IFI44L genes were knocked out; and c) knocking out the IFI44L gene also suppressed the expression of two interferon-induced proteins, IFIT2 and IFN-λ1.[3] (IFIT2[5][17] and IFN-λ1[18] proteins inhibit the growth and replication of various viruses.) These studies indicate that the IFI44L protein promotes the proliferation of these three viruses in their respective cultured cells and appears to do so by inhibiting them from making two inhibitors of viral growth/proliferation, i.e., the type I interferon-stimulate IFIT2 and type III interferon-simulated IFN-λ1 proteins.[3] A study of 32 patients who had SARS-CoV-2, (a form of coronavirus that causes covid-19) for 5 to 17 weeks reported that 15 patients with symptomatic covid-19 disease had significantly higher blood cell levels of IFI44L mRNA than 17 patients who did not develop symptoms of this infection. The study suggested that high blood cell levels IFI44L mRNA may contribute to the develop of symptoms in patients with covid-19 infections.[19] An epigenome-wide association study on the DNA methylation of genes in individuals with Covid-19 reported that CpG sites (i.e., cytosine-phosphate-guanine sites) in a promotor (identified as the cg03607951 site ) of the IFI44L gene in the blood cells of 109 patients with Covid-19 had significantly lower levels of cytosine methylation than 71 non-infected individuals.[1] Low levels of cytosine methylation in a gene's CPG promotor are generally associated with increases in the expression of this promotor's gene.[1][20] The study suggested that high levels of IFI44L promote the development of symptomatic Covid-19.[1][14]

Hepatitis B virus

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Hepatitis B virus (i.e., HBV) causes a form of hepatitis that is often chronic and leads to cirrhosis, cancer, and failure of the liver. HBV is a DNA virus that infects hepatocytes (i.e., liver cells) in the form of a virion (i.e., particle) with its genetic material in the form of relaxed circular DNA (i.e., rcDNA).[21] Once inside the hepatocyte, it replicates by converting its rcDNA to covalently closed circular DNA (i.e., cccDNA: see rcDNA and cccDNA). cccDNA forms the proteins that transcribe the HBV DNA into mRNA and translate this mRNA into proteins that make HBV virions which leave the cell to infect other hepatocytes.[22] As of 2024, there were 7 medications licensed to treat chronic HBV hepatitis B infection in the United States[23](see treatment of chronic HBV hepatitis). These medications suppress the replication of HBV but do not remove all the HBV cccDNA, i.e., these drugs as well as various experimental treatments do not completely eliminate or inactivate cccDNA and therefore do not cure HBV-induced chronic hepatitis.[21][22][24] A study [21]quantified the HBV virions made by cultured Hep G2 human hepatocellular carcinoma cells by: a) infecting cultured HepG2 cells with a form of HBV that causes severe liver damage in humans; b) adding the extracellular media of these Hep 2G cultures to cultures of PXB cells (i.e., human hepatocytes isolated from humanized PBX-mice); c) treating the cultured PXB cells with IFN-α or a type II interferon, IFN-γ, on days 4, 8, 13, 18, and 23 days; and measuring the effects of this treatment on the PXB cells' the production of the HBV virion. The experiment showed that the PXB culture media developed progressively increasing levels of HBV virions and the surface antigen of HBV virion, i.e., HBsAg and the PXB cells accumulated increasing levels of cccDNA and IFI44L mRNA as well as HBV virions and HBsAg over this 23 day time period. Knockdown of IFI44L in the cultured PBX cells significantly reduced the levels of extracellular HBV virions and HBsAg and intracellular HBV virions, HBV RNA, and cccDNA caused by either INF-α or INF-γ. Thus, the anti-HBV effect of IFI44L is exerted regardless of IFN-γ and IFN-α.[14][21] Finally, a study Cite error: A <ref> tag is missing the closing </ref> (see the help page). a)rs273259, a missense gene variant (i.e. a variant that causes a change in the amino acid sequence of the protein) in exon 2 of the IFI44L gene that has a quinine rather than adenine nucleotide thereby coding for a histidine rather than arginine at position 73 in the IFI44L protein (change notated as His73Arg[25]);[26] and b) rs1333969 which has an intronic change (i.e., a change that does not alter the ammino acid sequence of the IFI44L protein) of cytosine to either thymine or adenine nucleotide in the IFI44L gene.https://www.ncbi.nlm.nih.gov/snp/rs1333969/ In the STEPS study, children with the rs273259 or rs1333969 forms of the IFI44L gene had a decreased number of days they had RTI symptoms and a decreased rate of developing acute otitis media from birth to 2 years of age. In the FinnBrain Birth Cohort Study, children with the rs273259 and rs1333969 variants of this gene had a decreased rate of developing RTIs during their first year of life. Children with either variant had significant decreases in the expression of the IFI44L protein. The study concluded that these variant IFI44L gene reduced the expression or their IFI44L proteins and these reductions were associated with decreased rates of developing RTIs and acute otitis media.[25]

Other viral infections

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Studies have shown that IFI44L mRNA in the peripheral blood or certain peripheral blood cells is elevated in: a) 11 febrile children aged 1 to 6.4 years old with various viral infections;[27] b) 92 children (median age 1.5 years) with various viral infections;[28] b) febrile infants up to 60 days old with neutropenia caused by various viral infections;[29] c) 59 children less than 14 years of age with a febrile illness due to various viruses;[30] and d) 212 adult patients with an acute febrile illness caused by various viruses.[31] In each of these studies, the levels of IFI44L mRNA were significantly higher in patients with various viral infections than similar numbers of patients with various bacterial infections. These studies suggest that measurements of IFI44L mRNA levels may prove useful for distinguishing viral from bacterial infections in infants, children, and adults.[27][28][29][30][31]

Bacterial infections

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Mycobacterium tuberculosis

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A study testing the function of the IFI44L gene in Mycobacterium tuberculosis (the bacterium that causes tuberculosis) reported that cultures of a macrophage cell line derived from the THP-1 human monocytic cell line developed higher mRNA levels and lower levels of four inflammation-promoting cytokines, (i.e., CCL4, CXCL10, CXCL11, and IL18) after being infected with the H37Rv strain of mycobacterium tuberculosis. The survival of these mycobacteria was greatly increased in macrophages that had their IFI44L gene knocked out. In addition, the levels of IFI44L mRNA rose while the survival of H37Rv mycobacteria and levels of the cited inflammatory cytokines fell in macrophages pretreated with rifampicin, a mycobacterium-killing drug. Finally, rifampicin- based anti-tuberculosis drug treatment of 10 patients with the cutaneous form tuberculosis for 1 to 6 months had decreases in their tubercular skin lesions and decreases in their PMBCs levels of IFI44L mRNA, IFI44L protein, and the cited cytokines. These studies suggest that the IFI44L protein acts to clear mycobacterium from cultured macrophages and mycobacterial skin lesions and may do so, at least in part, by promoting production of pro-inflammatory cytokines. The data support future studies to determine if the IFI44L gene is a target for therapeutic strategies to treat Mycobacterium tuberculosis and a useful biomarker for determining the effectiveness of antituberculosis therapy.[32] A second study reported that 92 patients with tuberculosis had higher levels of IFI44L in their peripheral blood than 61 healthy controls.[33]

Other bacterial infections

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Studies examining various bacterial infections (see above "Other viral infections" section) suggest that, except for Mycobacterium tuberculosis', many types of bacterial infections are not associated with appreciable activations of the IFI44L gene as defined by rises in IFI44l mRNA levels. However, these studies often did not define the types of bacteria examined. Further studies are needed on a wide range and larger sampling of bacteria to support this conclusion.[27][28][29][30][31]

Cancers

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Squamous-cell carcinoma of the head and neck

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Squamous-cell carcinoma of the head and neck are head and neck cancers derive from the mucosal epithelium in the oral cavity, pharynx (which includes the hypopharynx), and larynx. They consist mostly of and therefore are termed collectively as head and neck squamous cell carcinoma, i.e., HNSCC.[34] A study reported that the cells in the HNSCC of patients had significantly higher levels of IFI44L protein (as defined using antibodies directed at this protein) than cells in nearby normal head, neck, and epithelium tissues. Similarly, four immortalized human cell lines, FaDu cells (i.e., cells derived from a squamous cell carcinoma of the hypopharynx[35]), HSC‐3 cells (i.e., cells derived from a tongue cancer[36]), SAS cells (i.e., cells derived from a tongue squamous cell carcinoma[37]), and human embryonic kidney 293 T cells had higher IFI44L protein levels than HOK cells (i.e., cells derived from non-cancerous oral keratinocytes).[2] Long-chain-fatty-acid—CoA ligase 4, also termed long‐chain acyl‐CoA synthetase 4 or ACSL4, is an enzyme that catalyzes fatty acids to form fatty acyl-CoA esters.[2] It is also implicated in increasing the invasiveness, migration, and survival of cultured colon, prostate, breast, lung, and brain cancer cells.[38][39] Similar to IFI44L, ACSL4 protein levels were higher in patient's HNSCC tumor tissues than their nearby normal head, neck, and epithelial tissues. Furthermore, patients with HNSCC tumors that expressed higher levels of ACSL4 protein had significantly shorter survival times than patients with lower ACSL4 protein levels. Finally, cultured OECM‐1 (a human oral squamous carcinoma cell line[40]), SAS, and HSC‐3 cells that had their ACSL4 protein levels reduced using short hairpin RNAs showed significantly decreased levels of IFI44L as well as their rates of proliferation, migration, and invasiveness than the same cell lines that were treated with inactive short hairpin RNAs that did not alter the levels of ACSL4 protein. Thus, high IFI44LK protein levels promote the malignant behavior of cultured HNSCC tumor cells; high levels of ACSL4 protein cause high levels of IFIL44; high levels of ACSL4 and IFI44L are associated with increase aggressiveness of HNSCC and decreased survival times of patients with HNSCC; these actions of high ACSL4 levels may be caused, at least in part, by its promoting increases in IFIL44; and IFI44L and ACSL4 may prove useful parameters of disease severity and therapeutic targets for treating HNSCC.[2] In two other studies, IFI44L mRNA levels were found to be far higher in the nasopharyngeal carcinomas than normal nasopharyngeal tissues based on a large number of samples in the Gene Expression Omnibus[41] and IFI44L mRNA levels were reported to be significantly higher in 209 oral squamous cell carcinomas than normal oral tissues with carcinomas having high levels of IFI44L mRNA associated with poorer overall survival rates.[14][42] Finally, podoplanin, a protein often found in squamous cell carcinomas, was expressed in the TW01 nasopharyngeal cancer cell line. Suppressing podoplanin's levels in cultured TW01 cells inhibited their proliferation, motility, invasiveness, and viability and increased their expression of IFI44L mRNA. This study suggested that activation of the IFI44L gene may contribute to the inhibitory effects caused by suppressing podoplanin's levels.[43]

Hepatocellular carcinoma

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A study reviewing 217 patients with hepatocellular carcinoma in China reported that the levels of IFI44L protein in their carcinomas were significantly lower in patients who had larger tumor sizes, advanced stage disease, a relapse in their disease, and/or shorter survival times. This study also examined cultures of human Hep3B, Hep G2, and PLC hepatocarcinoma cells or the stem cells cells isolated from these hepatocarcinoma cell lines.[4](Stem cells are a small subset of cells in cancers that self-renew, continuously proliferate, form tumors, metastasize, and maintain tumor heterogeneity.[44]). These culture cell studies showed that the forced overexpression of IFI44L protein by transfection with a plasmid containing the human IFI44L gene into Hep3B cells, Hep G2 cells, or the stem cells isolated from these these two cell lines increased their sensitivity to the lethal effects of doxorubicin; reducing IFI44L protein levels using small interfering RNA restored these cells' resistance to this chemotherapy drug. Finally, depletion of the IFI44L gene in cultures of Hep3B, Hep G2, and PLC cells using a gene knockdown method enhanced their migration and tissue invasiveness as measured by in vitro assays as well as pulmonary metastasis as measured by injecting these cells into 6-8-week-old severe combined immunodeficient mice. These results suggest that the IFI44L gene is a tumor suppressor gene for hepatocellular carcinoma at least in the cited Chinese population and, if confirmed in future studies including those conducted outside of China, would indicate that INI44L protein levels can be used as a predictive biomarker of hepatocellular disease severity and a promising therapeutic target (i.e., by lowering its levels) for treating hepatocellular carcinoma.[4]

Non-small cell lung cancer

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A study[45] on two forms of non-small cell lung cancer, lung adenocarinoma (LAD) and lung squamous cell carcinoma (LSC), reported that: a) cell culture assays on the growth, proliferation, and invasiveness of two human lung cancer immortalized cell lines representing LAD and LSC cells, i.e. SPC-A-1 and NCI-H520 cells, respectively, were inhibited by forcing these cells to overexpress the IFI44L gene; b) IFI44L mRNA levels were significantly lower in 497 LAD and 489 LSC tissues than in normal lung tissues; c) the levels of IFI44L mRNA in LAD and LSC tissues increased with increases in the numbers of inflammation-producing and potentially tumor-suppressing immune cell types in these tissues but decreased with the number of relatively inactive or tumor tolerance-promoting types of immune cells in these tissues; and d) dividing LAD and LSC into high and low scores based on the number and types of immune cells in patient LAD and LSC tissues successfully classified patients into low risk and high risk groups with the low risk group having a significantly longer overall survival rate rate than patients in the high risk group. These studies indicate that overexpression of the IFI44L gene inhibits the growth of of cultured SOC-A-1 (i.e., LAD-like) and NCI-h520 (i.e., LSC-like) forms of non-small cell lung cancer, that treatments which stimulate the IFI44L gene may be therapeutically useful for treating these cancers, and that measurements of the levels of the various immune cell types in these cancers offers an indicator for these tumors' aggressiveness and patient survivals.[14][45] A subsequent study[46] found that non-malignant human bronchial epithelial cells (i.e., HBE cells) responded to treatedment with a cancer-causing chemical, 3-methylcholanthrene, by significantly decreasing their levels of IFI44L mRNA and protein. This study also showed that: a) compared to normal lung tissue, the levels of IFI44L mRNA and IFI44L protein were low and methylations of the IFI44L gene at three sites (i.e., cg17980508, cg03607951, and cg27315157) were increased in 486 cases of human lung adenocarcinoma; b) expression of the IFI44L gene was decreased in adenocarcinoma tissues with higher levels of methylation at these three IFI44L gene sites; c) the forced overexpression of IFI44L mRNA in two human lung cancer cell lines that express low levels of IFI44L mRNA, i.e., SPC-A1 cells (cells with characteristics of cancer stem cells[47]) and LTEP-a-2 cells (i.e., cells used in Asian studies of lung cancer[48]) decreased their rate of proliferation and increased their apoptosis (i.e., cell death) while knockdown of the IFI44L gene in A549 cells, which normally express high levels of IFI44L, increased their rate of proliferation and decreased their apoptosis; and d) in a model of in vivo cancer cell growth, nude mice (i.e., mice that have a defective immune system) that were subcutaneously injected with human lung cancer cells that were forced to overexpress the IFI44Lgene grew more slowly than the tumors produced by the injection of human cancer cells that did not ocweexpress the IFI44l gene. These studies indicated that the IFI44L gene functions to inhibit the growth of certain types of human lung cancer cells in culture as well as in mice and suggest that this gene is a tumor suppressor gene.[14][46]

Other cancers

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A review study with various early stage (i.e., not advanced) lung cancers (127 patients), breast cancer (94 patients) or melanomas (15 patients) reported that the peripheral blood monocytes of these patients overexpressed the IFI44L protein compared to similar tissues taken form 148, 31, and 13, respectively, healthy individuals. These results suggest require formal and independent validation, they suggest that high levels of the IFI44L protein may prove to be a useful biomarker for identifying solid tumors at an early stage.[49]

Genetic disorders

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Aicardi–Goutières syndrome

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The Aicardi–Goutières syndrome (i.e., AGS) is a rare childhood genetic disorder caused by mutations in the TREX1, RNASEH2B, RNASEH2C, RNASEH2A, ADAR1, SAMHD1, IFIH1, LSM11, or RNU7-1 gene. Symptoms of the disease are most often detected in infants around 4 months of age but may be detectable in embryos.[50][51][50] These mutations lead to increased type I interferon production thereby triggering autoimmune inflammation-induced damage to nervous tissues that result in cerebral atrophy, various encephalopathies, spastic paraplegia, strokes, microcephaly, intellectual disability,[50] epilepsy, bradykinesia, and/or dystonia (i.e., involuntary, repetitive muscle contractions).[52] The elevated levels of type I interferons may also trigger inflammation-induced skin disorders such as chilblain-like lesions, acrocyanosis, fingernail abnormalities, the Raynaud syndrome, and/or endocrine diseases such as diabetes insipidus, diabetes mellitus, hyperparathyroidism, growth hormone deficiency, and adrenal insufficiency.[52] A recent study showed that the blood levels of mRNA for the IFI44L protein in 334 patients with AGS were higher than the proteins for 35 other interferon signaling genes. The study suggested that elevated IFI44L mRNA blood levels may be a useful marker for diagnosing AGS.[53] A study conducted in Italy examined patients with AGS caused by a mutation in the RNASEH2B gene. In addition to this mutation, 5 patients had a c.529G>A,p.A177T mutation in exon 7 of both of their RNASEH2B genes.[51] That is, the guanine (G) nucleotide at gene position 529 replaced an adenine (A) nucleotide to result in a change in the amino acid from alanine (A) to threonine (T) at position 177 in the mutated RNASEH2B protein.[54] Five AGS patients who had this doubly mutated RNASEH2B gene suffered far more severe forms of AGS than patients with just the singularly mutated RNASEM2B gene. Patients with the adenine form of RNASEH2B mutated protein had low levels of methylation in the promotor regions of the IFI44L gene and significantly higher levels of IFI44L mRNA in their peripheral blood mononuclear cells. If these findings are confirmed in in further studies, the authors suggest that high levels of IFI44L mRNA would be useful marker to diagnose AGS and support studies to determine if suppressing the expression of this gene would be useful for treatin AGS.[51]

Autoimmune diseases

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Systemic lupus erythematosus

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A study of Chinese and European patients with systemic lupus erythematosus (1521 patients), rheumatoid arthritis (782 patients), Sjögren's syndrome (199 patients), and 1703 healthy individuals reported that peripheral blood mononuclear cells of systemic lupus erythematosus (i.e., SLE) patients had significantly lower DNA methylation levels in the promoter sites of their IFI44L genes than rheumatoid arthritis patients, Sjögren's syndrome patients, and healthy individuals.[55] Low methylation levels at gene promotors usually increases the expression of these genes mRNAs and proteins.[56] A follow-up study found that these methylation levels in the IFI44L gene promotor were also lower in SLE patients than patients with discoid lupus erythematosus (i.e., a cutaneous and less severe from of SLE[57]).[58] The two studies suggest that these DNA methylations in the IFI44L gene promotor may be useful for diagnosing SLE from other autoinflammatory diseases including discoid lupus erythematosus.[55][58] A review of studies published up to and including July 2022 on methylations in the promotors of type I interferon-stimulated genes in SLE found 7 other studies besides the Chinese-European study that examined promoters to the IFI44L gene. These studies, which were done in China, Iran, and the USA, reported that IFI44L gene promotor methylations were lower in SLE patients than healthy individuals. However, 2 of these 7 studies (both done in Iran) reported that IFI44L promotor methylations were also lower in patients with rheumatoid arthritis than heathy individuals.[59] This[59] and another[60] review concluded that low methylation levels in the IFI44L gene promoter are a promising diagnostic biomarker for SLE but further studies are needed to determine if these low levels: a) discriminate SLE from rheumatoid arthritis or other autoimmune diseases that can have symptoms similar to and be mistaken for SLE; b) are related to the severity of SLE (e.g., is IFI44L promoter methylation low in mild cases of SLE?); and c) have not been accompanied by information on the diet regimens and drug consumptions which can effect these methylations. Finally, a recent study found that 36 of 49 children with childhood-onset systemic lupus erythematosus had lower methylation levels in the promoter region of their IFI44L gene (measured in the children's whole blood) than those of 12 healthy children. The study suggested that, while further studies are needed, IFI44l promoter methylation levels in children are similar to those found in adults.[61]

Rheumatoid arthritis

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References

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