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| References | Diseases | Study aim | Research contribution |
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| [53] | Hepatitis B virus (HBV) | To identify the possible causes and pathogenesis of hepatitis B-related acute chronic liver failure (HBV-ACLF); the analysis of the transcriptome of PBMCs has been applied. | DEFA4 gene was indicated as one of the genes that could serve as a potential biomarker for HBV-ACLF detection. |
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| [54] | Hepatitis B virus (HBV) | Analysis of the transcriptome of PBMCs to recognize the gene expression pathways that failed to trigger effective immune response after a hepatitis B vaccination. | DEFA4 gene was up-regulated in the non-responders. |
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| [56] | Hepatitis C virus (HCV) | Gene expression profiles were examined on peripheral blood samples from liver transplant recipients with HCV (n = 6) before and after the seven-day liver transplantation | DEFA4 was detected to be one of the 97 up-regulated genes (>2-fold) in liver transplant recipients with HCV seven days after liver transplantation compared with before transplantation |
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| [57] | Hepatitis E virus (HEV) | RNAseq analysis was applied to understand the causes of HEV in:
-Pregnant women (PR) at their 2nd and 3rd trimesters at two-phase acute and subclinical phases.
-Non-pregnant women (NPR) also with two phases acute and convalescent, all compared with healthy subjects. | The result indicated that there was no presence of DEFA4 in NPR women at all phases while it was up-regulated in all phases for PR women. |
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| [67] | Asthma | To determine the differences between asthma and non-asthma groups, as well as stratify potential subgroups depending on gene expression of blood samples. | DEFA4 was one of the genes that showed significantly higher gene expression in patients with severe asthma compared with healthy individuals. |
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| [68] | Asthma | This study aimed to distinguish between different phenotypes of asthma in children through examining gene expression profiles of PBMCs. | (i) DEFA4 was identified as one of the 19 up-regulated genes in neutrophil-predominant asthma compared with other asthma phenotypes.
(ii) 40% of non-responders to corticosteroid treatment were suffering neutrophil-predominant asthma. |
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| [69] | Idiopathic pulmonary fibrosis (IPF) | In this study, gene expression profile analysis of blood samples was performed to identify biomarkers that would enable determining the severity and monitoring the progression of IPF. | DEFA4 was reported as one of 13 differentially expressed genes that can distinguish between mild and severe IPF cases, wherein DEFA4 was up-regulated in severe cases. |
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| [70] | Idiopathic pulmonary fibrosis (IPF) | This study aimed to examine the gene expression profiles from blood samples of IPF patients compared to controls at the baseline and longitudinal follow-up after (1, 3, 6) months as well as one year (if alive) to monitor changes in the gene expression over time. | DEFA4 was one of the top up-regulated genes in IPF subjects versus controls.
-Moreover, DEFA4 was one of the most significant genes that showed higher expression in IPF patients over 12 months. |
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| [59] | Coronavirus disease 2019 (COVID-19) | Multi-omic analysis was conducted on blood samples of COVID-19-positive patients (n = 102) and COVID-19-negative patients (n = 26) to provide insight into COVID-19 pathophysiology and prediction of its severity. | Increased DEFA4 expression was reported as one of 219 molecular features that significantly correlated to COVID-19 status and severity. |
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| [73] | Periodontitis | In order to understand the pathogenic process in periodontitis, by RT-qPCR, the expression levels of several AMPs genes were measured in gingival smears from 12 patients with moderate or severe chronic periodontitis and 11 healthy subjects. | (i) DEFA4 was one of three genes identified to be associated with periodontal health. DEFA4 was observed to be down-regulated in the periodontitis patients compared with healthy controls.
(ii) Moreover, a significant positive correlation was recorded between the expression level of the DEFA4 gene and the presence of Porphyromonas gingivalis and Parvimonas micra. |
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| [74] | Systemic lupus erythematos-us (SLE) | This study suggests that the low-density granulocytes (LDGs) have a substantial role in the pathogenesis of lupus erythematosus through the comparison with autologous normal-density neutrophils and control neutrophils. | DEFA4 gene was among the genes found to be up-regulated in LDGs. |
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| [75] | Systemic autoimmune diseases (SAID) | RNA microarray analysis has been applied to indicate the gene expression in PMBC from 20 monozygotic twin pairs discordant for multiple SAID as well as 40 unrelated control subjects. | DEFA4 gene was noticed to be up-regulated in subjects with SAID compared to unrelated, matched controls. |
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