Serum IFN-α Levels Research Articles

CCL4 as a potential serum factor in differential diagnosis of central nervous system inflammatory diseases and gliomas.

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are commonly utilized to detect brain gliomas and central nervous system inflammation diseases. However, there are instances where depending solely on medical imaging for a precise diagnosis may result in unsuitable medications or treatments. Pathological analysis is regarded as the definitive method for diagnosing brain gliomas or central nervous system inflammation diseases. To achieve this, a craniotomy or stereotaxic biopsy is necessary to collect brain tissue, which can lead to complications such as cerebral hemorrhage, neurological deficits, cerebrospinal fluid leaks, and cerebral edema. Consequently, the advancement of non-invasive or minimally invasive diagnostic techniques is currently a high priority. This study included samples from four glioma patients and five patients with central nervous system inflammatory diseases, comprising both serum and paired cerebrospinal fluid (CSF). A total of 40 human cytokines were identified in these samples. We utilized a receiver operating characteristic (ROC) analysis to assess the sensitivity and specificity for distinguishing central nervous system inflammation diseases and gliomas. Additionally, we examined the correlation of these factors between serum and CSF in the patients. Ultimately, the identified factors were validated using serum from patients with clinically confirmed gliomas and central nervous system inflammation diseases followed by detection and statistical analysis through ELISA. The levels of serum factors IL-4, IFN-α, IFN-γ, IL-6, TNF-α, CCL4, CCL11, and VEGF were found to be significantly higher in gliomas compared with inflammatory diseases of the central nervous system (p < 0.05). Furthermore, a strong correlation was observed between the levels of CCL4 in serum and CSF, with a correlation coefficient of r = 0.92 (95% CI = 0.20-0.99, p = 0.027). We gathered more clinical samples to provide further validation of the abundance of CCL4 expression. A clinical study analyzing serum samples from 19 glioma patients and 22 patients with central nervous system inflammation diseases revealed that CCL4 levels were notably elevated in the inflammatory group compared with the glioma group (p < 0.001). These results suggest that assessing serum CCL4 levels may be useful in distinguishing those patients for clinical diagnostic purposes.

Pathogenic role and diagnostic utility of interferon-α in histiocytic necrotizing lymphadenitis

PurposeHistiocytic necrotizing lymphadenitis (HNL) is an inflammatory disease of unknown etiology clinically characterized by painful lymphadenopathy. This study aimed to investigate the role of interferon (IFN)-α in the pathogenesis of HNL and the clinical significance of serum IFN-α levels for the diagnosis and monitoring of HNL disease activity. MethodsThis study enrolled 47 patients with HNL and 43 patients with other inflammatory diseases that require HNL differentiation including malignant lymphoma (ML), bacterial lymphadenitis, and Kawasaki disease. Expression of IFN-stimulated genes (ISGs) and MX1 in the lymph nodes was measured by real-time quantitative reverse transcription polymerase chain reaction and immunofluorescence staining, respectively. Enzyme-linked immunosorbent assay was used to quantify serum cytokine levels. The results were compared with the clinical features and disease course of HNL. ResultsPatients with HNL had a significantly elevated ISG expression in the lymph nodes compared with those with ML. MX1 and CD123, a specific marker of plasmacytoid dendritic cells (pDCs), were colocalized. In patients with HNL, serum IFN-α levels were significantly elevated and positively correlated with disease activity. The serum IFN-α level cutoff value for differentiating HNL from other diseases was 11.5 pg/mL. ConclusionIFN-α overproduction from pDCs may play a critical role in HNL pathogenesis. The serum IFN-α level may be a valuable biomarker for the diagnosis and monitoring of disease activity in patients with HNL.

Innate Responses to the Former COVID-19 Vaccine Candidate CVnCoV and Their Relation to Reactogenicity and Adaptive Immunogenicity.

Vaccines are highly effective at preventing severe coronavirus disease (COVID-19). With mRNA vaccines, further research is needed to understand the association between immunogenicity and reactogenicity, which is defined as the physical manifestation of an inflammatory response to a vaccination. This study analyzed the immune response and reactogenicity in humans, post immunization, to the former SARS-CoV-2 mRNA investigational vaccine CVnCoV (CV-NCOV-001 and CV-NCOV-002 clinical trials). Immunogenicity was investigated using whole-blood RNA sequencing, serum cytokine levels, and SARS-CoV-2-specific antibodies. The T cell responses in peripheral blood were assessed using intracellular cytokine staining (ICS) and high-dimensional profiling in conjunction with SARS-CoV-2 antigen-specificity testing via mass cytometry. Reactogenicity was graded after participants' first and second doses of CVnCoV using vaccine-related solicited adverse events (AEs). Finally, a Spearman correlation was performed between reactogenicity, humoral immunity, and serum cytokine levels to assess the relationship between reactogenicity and immunogenicity post CVnCoV vaccination. Our findings showed that the gene sets related to innate and inflammatory immune responses were upregulated one day post CVnCoV vaccination, while the gene sets related to adaptive immunity were upregulated predominantly one week after the second dose. The serum levels of IFNα, IFNγ, IP-10, CXCL11, IL-10, and MCP-1 increased transiently, peaking one day post vaccination. CD4+ T cells were induced in all vaccinated participants and low frequencies of CD8+ T cells were detected by ex vivo ICS. Using mass cytometry, SARS-CoV-2 spike-specific CD8+ T cells were induced and were characterized as having an activated effector memory phenotype. Overall, the results demonstrated a positive correlation between vaccine-induced systemic cytokines, reactogenicity, and adaptive immunity, highlighting the importance of the balance between the induction of innate immunity to achieve vaccine efficacy and ensuring low reactogenicity.

Expressions of Type I-III Interferons in Sjögren's Syndrome and Non-Sjögren's Dry Eye.

Systemic implications create a critical need for identification of dry eye patients with Sjögren syndrome (SS). Herein, we aimed to determine expressions of type I-III interferons (IFNs) in dry eye patients with or without underlying SS and their differential diagnosis. A prospective, observational, case-control study was performed on 140 dry eye patients among which 78 patients were diagnosed with SS. Clinical evaluations included ELISA detections of serum type I IFN (IFN-α and IFN-β, type II IFN (IFN-γ), and type III IFN (IFN-λ1/IL-29, IFN-λ2/IL-28, and IFN-λ3/IL-28B), as well as reporter cell assay for serum type I IFN activity. The serum levels of IFN-α and IFN-β were notably higher in dry eye patients with SS than those without underlying SS (p &lt; 0.0001). The functional assay for serum type I IFN activity showed the mean summed scores in dry eye patients with SS were remarkably increased compared to those without underlying SS (p &lt; 0.0001). The serum levels of IFN-γ and IFN-λ1/IL-29 seemed higher in dry eye patients with SS than those without underlying SS (p &lt; 0.0001). The serum levels of type I IFN (IFN-α combined with IFN-β), type II IFN (IFN-γ level), and type III IFN (IFN-λ1/IL-29) used as a test to predict underlying SS among dry eye patients produced an area under the curve of 0.86, 0.73, and 0.94, respectively. Serum levels of type I-III IFNs, especially IFN-α, IFN-β, and IFN-λ1/IL-29, may serve as a useful biomarker for identification of SS dry eye from non-SS dry eye.

TREX1 Mutations in Aicardi–Goutières Syndrome with Congenital Glaucoma

TREX1 Mutations in Aicardi–Goutières Syndrome with Congenital Glaucoma

Regulation of CD47 expression on CD14+ monocytes by interferon-α in PBC patients.

Primary biliary cholangitis (PBC) is a chronic intrahepatic cholestatic autoimmune liver disease characterized by inflammatory injury of small and medium-sized bile ducts in the liver. The pathogenesis of PBC has yet to be entirely understood. CD47/signal-regulatory protein alpha (SIRPα) is closely related to developing autoimmune diseases by promoting inflammatory response. However, the effect of CD47/SIRPα on inflammatory response in PBC patients is still unclear. We investigated the expression of CD47/SIRPα and the effect of inflammatory cytokines on the CD47 expression, analyzed potential autoantibodies against CD47 and the effect of anti-CD47 antibody on the inflammatory response in PBC, provided laboratory basis for the study of the pathogenesis and targets for non-invasive diagnosis and treatment on PBC. The expression levels of CD47 and SIRPα on peripheral blood mononuclear cells (PBMC) were measured in 14 patients with PBC (the PBC group) and 13 healthy subjects (the Control group) by flow cytometry (FCM). The PBMC derived from healthy subjects were stimulated with healthy subjects' serum, PBC patients' serum, IFN-α or TNF-α, and the CD47 expression level on CD14+ monocytes was detected by FCM. The level of serum anti-CD47 antibody or IFN-α in PBC patients and healthy subjects was analyzed by ELISA. FCM was used to examine the TNF-α expression level in CD14+ monocytes of healthy subjects stimulated with isotype control antibody, anti-CD47 antibody, LPS or LPS combined with CD47 antibody. The CD47 expression level on the CD14+ monocytes in PBC patients was statistically higher than that in the Control group (P<0.01). Compared with the Control group (PBMC+healthy serum), the CD47 expression on CD14+ monocyte stimulated with the PBC patients' serum (PBMC+PBC patients' serum) was increased (P<0.001); the CD47 expression on CD14+ monocyte stimulated with IFN-α (PBMC + IFN-α) increased gradually with the increased concentration of IFN-α (P<0.05). However, there was no similar trend on CD14+ monocyte stimulated with the TNF-α (PBMC+TNF-α) (P>0.05). The levels of serum anti-CD47 antibody and IFN-α in the PBC patients were higher than those in healthy subjects (P<0.05). The TNF-α expression level in CD14+ monocyte stimulated with the LPS (PBMC+LPS) or anti-CD47 antibody+LPS group (PBMC+LPS+anti-CD47 antibody) was significantly increased than that in the Control group (PBMC+isotype control antibody) (P<0.01 and P<0.001, respectively). The TNF-α expression level in CD14+ monocyte stimulated with the anti-CD47 antibody + LPS was higher than that with the LPS (P< 0.05). The CD47 may be related to the pathogenesis of PBC by inflammatory response. The CD47/SIRPα signal were imbalanced in PBC patients. The presence of serum anti-CD47 antibodies in PBC patients provides a laboratory basis for clinical diagnosis and treatment.

Serum interferon-alpha predicts in-hospital mortality in patients hospitalised with acute severe lupus

ObjectivesDysregulation of interferon-alpha (IFN-α) is considered central to the immunological abnormalities observed in SLE. Short-term mortality during high disease activity in lupus is up to 30%. Adenovirus vector-introduced IFN-α into...

Host immunity and HBV S gene mutation in HBsAg-negative HBV-infected patients.

Clinically, some patients whose HBsAg becomes negative owing to antiviral therapy or spontaneously still show a low level of HBV DNA persistence in serum. T-lymphocyte subsets, cytokine levels and HBV S gene sequences were analyzed in this study. A total of 52 HBsAg-negative and HBV DNA-positive patients(HBsAg-/HBV DNA+ patients), 52 persistently HBsAg-positive patients(HBsAg+/HBV DNA+ patients) and 16 healthy people were evaluated. T-lymphocyte subsets of these patients were detected by flow cytometry, serum cytokines and chemokines were detected by the Luminex technique, and the HBV S region was evaluated by Sanger sequencing. T%, T-lymphocyte, CD8+ and CD4+T lymphocyte were lower in the HBsAg-negative group than in the HC group. Compared with the HBsAg-positive group, the HBsAg-negative group had lower levels in T lymphocyte %, CD8+T lymphocyte %, CD8+T lymphocyte and CD4/CD8. These difference were statistically significant (P<0.05). Serum IFN-γ, IFN-α and FLT-3L levels were significantly higher in the HBsAg-negative group than in the HBsAg-positive group (P<0.05). However, levels of many cytokines related to inflammation (i.e., IL-6, IL-8, IL10, IL-12, IL-17A) were lower in the HBsAg-negative group. Fifty-two HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., Y100C, S114T, C124Y, P127L, G130R, T131N, M133T, C137S, G145A) and TMD region substitutions (i.e., E2K/R/D, G7D/R, G10D, A17R, F20L/S, L21V, L22V). According to the results of T-lymphocyte subsets and serum cytokines, it can be deduced that the cellular immune function of HBsAg-negative patients is superior to that of HBsAg-positive patients, with attenuation of liver inflammation. HBsAg-negative patients may show a variety of mutations and amino acid replacement sites at high frequency in the HBV S region, and these mutations may lead to undetectable HBsAg, HBsAg antigenic changes or secretion inhibition.

Serum levels of type I interferon (IFN-I) is associated with the severity of COVID-19.

Introduction. Caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, coronavirus disease 2019 (COVID-19) has threatened global public health. Immune damage mechanisms are essential guidelines for clinical treatment and immune prevention.Hypothesis. The dysregulated type I interferon (IFN-I) responses, lymphocytopenia and hypercytokinemia during SARS-CoV-2 infection have been reported. However, whether there is a correlation between levels of IFN-I and the severity of COVID-19 has not been reported yet.Aim. To investigate the source of IFN-I and detect the exact roles of them in the pathogenesis of COVID-19.Methodology. Here ELISA was used to detect serum IFN-I (IFN-α and IFN-β) for 137 cases with laboratory-confirmed COVID-19 admitted into one hospital in Wuhan from December 2019 to March 2020, and the relationships between IFN-α/β concentrations and patients' clinical parameters were conducted by statistical analysis.Results. Both IFN-α and IFN-β concentrations dramatically increased in COVID-19 patients, especially in old patients (>80 years) and severe cases. Statistical analysis demonstrated that serum IFN-α/β concentrations were negatively correlated with the counts of total CD3+T, CD4+ and CD8+T cells, especially in critically ill cases. Moreover, serum IFN-α levels were positively correlated to IL-6 and TNF-α. Finally, immunofluorescent double staining showed that IFN-α and IFN-β are major secretions from macrophages and dendritic cells (DCs) in lymph nodes from COVID-19 autopsies.Conclusion. These results demonstrate that macrophages and DCs are the main origination of IFN-I, and serum levels of IFN-I are positively associated with lymphopenia and cytokine storm, suggesting that IFN-α/β deteriorated the severity of COVID-19. Anti-interferon or IFN-I signalling block drugs are needed to treat ICU patients.

Evaluation of the interaction between tumor growth factor-β and interferon type I pathways in patients with COVID-19: focusing on ages 1 to 90 years

BackgroundEvidence revealed that age could affect immune responses in patients with the acute respiratory syndrome of coronavirus 2 (SARS-CoV-2) infection. This study investigated the impact of age on immune responses, especially on the interaction between the tumor growth factor-β (TGF-β) and interferon type-I (IFN-I) axes in the pathogenesis of novel coronavirus disease 2019 (COVID-19).MethodsThis age-matched case–control investigation enrolled 41 COVID-19 patients and 40 healthy controls categorized into four groups, including group 1 (up to 20 years), group 2 (20–40 years), group 3 (40–60 years), and group 4 (over 60 years). Blood samples were collected at the time of admission. The expression of TGF-βRI, TGF-βRII, IFNARI, IFNARII, interferon regulatory factor 9 (IRF9), and SMAD family member 3 (SMAD3) was measured using the real-time PCR technique. In addition, serum levels of TGF-β, IFN-α, and SERPINE1 were measured by the enzyme-linked immunosorbent assay (ELISA) technique. All biomarkers were measured and analyzed in the four age studies groups.ResultsThe expression of TGF-βRI, TGF-βRII, IFNARI, IFNARII, IRF9, and SMAD3 was markedly upregulated in all age groups of patients compared with the matched control groups. Serum levels of IFN-α and SERPINE1 were significantly higher in patient groups than in control groups. While TGF-β serum levels were only significantly elevated in the 20 to 40 and over 60 years patient group than in matched control groups.ConclusionsThese data showed that the age of patients, at least at the time of admission, may not significantly affect TGF-β- and IFN-I-associated immune responses. However, it is possible that the severity of the disease affects these pathway-mediated responses, and more studies with a larger sample size are needed to verify it.

CD169 expression on monocytes as a marker for assessing type I interferon status in pediatric inflammatory diseases

BackgroundEvaluation of type I interferons (IFNs) in inflammatory or autoimmune diseases is challenging because of their rapid clearance in peripheral blood. The IFN gene expression signature has recently been used to evaluate the IFN status; however, this is often a labor-intensive and time-consuming procedure. Therefore, we assessed the feasibility of measuring expression of an IFN-inducible protein, CD169 (Siglec-1), on monocytes and circulating levels of soluble CD169 as alternative markers for type I IFN status in various pediatric inflammatory diseases. MethodsData from flow cytometric analysis of surface CD169 on monocytes and an enzyme-linked immunosorbent assay of soluble CD169 in peripheral blood were compared with serum IFN-α levels in 8 patients with viral infections, 5 with bacterial infections, 10 with systemic lupus erythematosus (SLE), 5 with Kikuchi-Fujimoto disease (KFD), 7 with Kawasaki disease (KD), and 8 with inflammatory bowel disease (IBD), and in 8 healthy controls. ResultsSurface CD169 expression was detected mainly on CD14+ monocytes and was significantly increased in patients with viral infections, SLE, and KFD, but not in patients with bacterial infections, KD, and IBD. There were similar trends for circulating soluble CD169; however, there was a significant increase only in patients with viral infections. Surface CD169 levels were significantly correlated with serum levels of IFN-α and soluble CD169. ConclusionAnalysis of CD169 expression on CD14+ monocytes may be useful for rapid assessment of type I IFN status for differentiation of pediatric inflammatory diseases from type 1 IFN-mediated diseases.

Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome

Laron syndrome (LS) is a rare genetic disorder characterized by low levels of insulin-like growth factor 1 (IGF1) and high levels of growth hormone (GH) due to mutations in the growth hormone receptor gene (GHR). A GHR-knockout (GHR-KO) pig was developed as a model for LS, which displays many of the same features as humans with LS-like transient juvenile hypoglycemia. This study aimed to investigate the effects of impaired GHR signaling on immune functions and immunometabolism in GHR-KO pigs. GHR are located on various cell types of the immune system. Therefore, we investigated lymphocyte subsets, proliferative and respiratory capacity of peripheral blood mononuclear cells (PBMCs), proteome profiles of CD4- and CD4+ lymphocytes and IFN-α serum levels between wild-type (WT) controls and GHR-KO pigs, which revealed significant differences in the relative proportion of the CD4+CD8α- subpopulation and in IFN-α levels. We detected no significant difference in the respiratory capacity and the capacity for polyclonal stimulation in PBMCs between the two groups. But proteome analysis of CD4+ and CD4- lymphocyte populations revealed multiple significant protein abundance differences between GHR-KO and WT pigs, involving pathways related to amino acid metabolism, beta-oxidation of fatty acids, insulin secretion signaling, and oxidative phosphorylation. This study highlights the potential use of GHR-KO pigs as a model for studying the effects of impaired GHR signaling on immune functions.

Интерфероны I типа, потребность в глюкокортикостероидах и коморбидность у пациентов с системной красной волчанкой

Background: сomorbidity is one of the factors which considerably reduce life expectancy and affect quality of life of patients with systemic lupus erythematosus (SLE). Interferons (IFNs) are molecules whose changing concentrations may induce the active clinical manifestations of SLE and the increase in risk of comorbidities and their higher severity. The involvement of IFN-α in the development of comorbidities in the adult population of SLE patients may have distinguishing characteristics in cases of childhood-onset SLE and will need further research for better understanding its role. Aim: to assess the relationship between the level of IFN-α and the need for glucocorticosteriods (GCs) and the prevalence of comorbidities in adult SLE patients with different onset ages. Patients and Methods: this non-interventional study included SLE patients (n=71) (SLICC (2012) / EULAR (2019) Criteria) who did not receive genetically engineered biological agents: 43 (60%) patients with SLE onset under the age of 18 years comprised the group of juvenile SLE (jSLE) and 28 (40%) patients with SLE onset at 18 years or older age were included in the group of adult SLE (aSLE). For determining SLE activity during physical examination of patients, the SLEDAI-2K index was used. Serum IFN-α levels were measured by enzyme-linked immunosorbent assay (ELISA). The Charlson comorbidity index (CCI) and the CIRS-G scale were used for assessing comorbidities. Results: in patients with aSLE, serum IFN-α levels were higher and associated with higher GC doses. Also, aSLE patients had higher CCI and CIRS-G scores. As regards comorbid diseases, a statistically significant higher prevalence of peptic (stomach and duodenal) ulcers and menstrual disorders in women was observed. These comorbidities correlated with IFN-α levels. Conclusion: serum IFN-α levels are associated with the use of high GS doses and high CCI and CIRS-G scores, as well as the prevalence of GI diseases and menstrual disorders in women. The anti-interferon therapy seems to be a promising option for reducing "steroid addiction" and related comorbidities. KEYWORDS: systemic lupus erythematosus, interferon, anifrolumab, glucocorticosteroids, comorbidity. FOR CITATION: Aliev D.B., Inamova O.V., Maslyansky A.L. et al. Type I interferon, the need for glucocorticosteroids and comorbidities in patients with systemic lupus erythematosus. Russian Medical Inquiry. 2023;7(3):118–123 (in Russ.). DOI: 10.32364/2587-6821- 2023-7-3-118-123.

Serum level of interleukin-6, interleukin-17A, and interferon-α in hospitalized COVID-19 patients and their clinical correlation: A hospital-based case–control study from North-East India

BACKGROUND AND OBJECTIVES: Dysregulation in the homeostasis of the cytokine pool induces severity in COVID-19 disease, which may result in poor clinical outcomes in severely ill patients. The main objective of this study was to evaluate serum interleukin-6 (IL-6), IL-17A, and interferon-α (IFN-α) in hospitalized COVID-19 patients and its association with the disease severity and clinical outcome. MATERIALS AND METHODS: Fifty-one hospitalized COVID-19 patients and 30 age- and sex-matched healthy volunteers were enrolled in this study. Serum IL-6, IL-17A, and IFN-α were quantified by enzyme-linked immunosorbent assay-based method. Receiver operating characteristic curve (ROC) analysis was performed for the cytokines. RESULTS: Serum IL-6, IL-17A, and IFN-α were significantly higher in COVID-19 patients than healthy control volunteers. Across severity groups, serum IL-6 was significantly higher in the severe group, whereas IFN-α was significantly higher in the mild–moderate group. Serum IL-6 was significantly higher in the deceased group compared to the recovered group. ROC analysis suggests that serum IL-6 can be used as a diagnostic and prognostic marker for severity and clinical outcome, respectively. CONCLUSION: Elevated levels of serum IL-6, IL-17A, and IFN-α in COVID-19 patients indicate cytokine dysregulation following severe acute respiratory syndrome coronavirus 2 infection. Elevated serum IL-6 was associated with disease severity and poor clinical outcome. Elevated IFN-α in mild–moderate group compared to the severe group signifies the antiviral effect of IFN-α may help in limiting disease severity in COVID-19 disease. Our data suggest that IL-6 can be used as a diagnostic and prognostic marker for disease severity and clinical outcome, respectively.

Effects of Escherichia coli strain Nissle 1917 on immune responses of Japanese quails (Coturnix japonica) to Newcastle disease vaccines.

The development of proper immune responses to Newcastle disease (ND) vaccines is important in controlling the disease. Escherichia coli strain Nissle 1917 (EcN) is involved in regulating the immune system. The current study evaluated the effects of EcN on immune responses to ND live vaccines in Japanese quails. A total of 150 one-day-old quails were divided into three equal groups. Groups A and B received 107 and 106 CFU/ml/day of EcN, respectively, sprayed on their diets, while group C received 1 ml/day of PBS. All birds were vaccinated with B1 and Lasota vaccines at 10 and 20 days of age, respectively. Serum samples were collected in order to assay the levels of IgA and certain cytokines, including IL4, IFN-α, and IFN-γ, as well as antibody titers to NDV by HI and ELISA methods. No significant difference (P>0.05) was observed in serum IgA and IFN-α levels among the groups. However, concentrations of IFN-γ and IL-4 in 42-day-old chicks in group A were significantly (P<0.05) higher than in both other groups. After 15 days of the second vaccination, the mean HI titer following NDV was significantly higher in group A than group C. Groups B and C showed significantly lower HI titer than group A after 22 days of the second vaccination. Mean ELISA titer to NDV was significantly (P<0.05) higher in group A than in groups B and C after 22 days of the second vaccination. It seems that the spraying of 107 CFU/ml/day of EcN on quail diets enhances the immune response to NDV vaccines by increasing serum levels of IFN-γ and IL-4.

Evaluation of Interferon Alpha (IFN-α) in Women with Systemic Lupus Erythematosus in Iraq

Systemic Lupus Erythematosus (SLE) is a multifactorial chronic systemic autoimmune disease. It is characterized by a lack of immune tolerance to autoantigens such as nuclear antigens. The aim of the study is to assess the interferon-alpha (IFN-α) serum level in Iraqi patients with SLE and determine its potential relation to different clinical and laboratory parameters and disease activity. 100 SLE patients were all females and with a mean of age 31.3 ± 10 years (16-63years) and disease duration of 5.8 ± 3.7years (1 month to 15 years). The average of SLEDAI score ranged from 2 to 22 with a mean of (8.53 ±3.42). Proteinuria, ESR, creatinine and AST were significantly higher (65% vs. 10% and 0.62±0.11 vs. 0.70±0.14 mg/dl respectively) while the PLT was significantly lower (231.9±88.8 vs. 282.3±67.3 103/mL) (p&lt; 0.001) among SLE patients as compared to control. Serum levels of IFN-α were increased in the SLE patients compared to control, and no significant difference has been observed (208.7±530.0 vs. 63.7±34.8 pg/ml) respectively (P=0.245). Interferon-alpha showed a significant negative correlation with the SLE Disease Activity Index (SLEDAI) in the active and inactive groups. There were no significant variations in all study parameters across IFN-α serum levels (p greater than 0.05). In conclusion, the results suggest a risk effect for female gender and age in etiology of SLE. IFN-α could not be considered as biomarker or to have a risk effect in SLE patients or perpetuate the disease activity. No evidence for any correlation between the IFN-α serum level and any clinical manifestations or laboratory investigation of the disease in current study except for age and disease duration, which suggests them as a risk factor for increasing the IFN-α serum level.

Lower disease activity but higher risk of severe COVID-19 and herpes zoster in patients with systemic lupus erythematosus with pre-existing autoantibodies neutralising IFN-α

ObjectivesType-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-β and/or IFN-ω subtypes are strong determinants of...

High prevalence of SARS-Coronavirus-2 in patients with inflammatory bowel disease and the role of soluble angiotensin converting Enzyme2

Context: Patients with inflammatory bowel disease (IBD) were found to have the higher intestinal expression of Angiotensin-Converting Enzyme2 (ACE2) that could consequently increase susceptibility to COVID-19 infection. Objective: This study reports the outcomes of COVID-19 infection in a large cohort of IBD patients. We compare levels of serum ACE and IFN-α between COVID19 patients with and without IBD. We performed a cross-sectional retrospective multicenter study. Methods: We enrolled patients with IBD screened for SARS-COV-2 in six medical centres in Iran from June to November 2020. The blood samples were drawn to measure COVID-19 IgM and IgG, and serum levels of sACE2, sACE1, and interferon-α, regardless of suspicious symptoms have done the molecular test. Results: A total of 534 IBD patients were included in the study. Of these, 109 (20.0%) cases had detectable IgG and IgM against SARS-CoV-2. sACE2 levels were higher in IBD patients than controls, whereas ACE1and IFN-α levels were similar among groups.

OA11 Serum interferon alpha levels as a predictor of short-term mortality in patients of SLE with high disease activity

Abstract Background/Aims Short-term mortality in patients with SLE and high disease activity approaches 30% as reported by various studies. Raised serum interferon-alpha levels are observed in patients with active SLE. In mice studies interferon alpha(IFNα) delivered through adenovirus vector to lupus prone mice, caused rapid development of glomerulonephritis and death within 18 weeks. The aim was to study the value of interferon alpha in predicting short-term mortality in patients of SLE with high disease activity. Methods Serum samples of consecutive SLE patients with high disease activity (SLEDAI&amp;gt;12) and age more than 18 years admitted in NIMS Rheumatology ward and acute medical care (AMC) were analyzed for interferon alpha levels with IFNα ELISA kit (ELAB science). Patients admitted for any other reason and having SLEDAI less than 12 were excluded. Demographic details and SLEDAI were recorded simultaneously. Patients who survived and discharged were considered as survivor group and those who succumbed during admission were considered as non-survivors. Between groups, difference in mean interferon alpha level was calculated using unpaired t test. Binomial logistic regression was applied to IFNα levels, dsDNA and SLEDAI as for predicting in-hospital mortality. Using ROC curve, area under curve was calculated for IFNα as a predictor of in-hospital mortality. Patients or legal guardian provided written informed consent for the study. Study was approved by the Institute ethics committee. Results Seventy patients with SLEDAI &amp;gt;12 were admitted to ward (n = 62) or AMC (n = 18) from November 2020 to August 2021.Those excluded were age&amp;lt;18 (n = 6), SLEDAI&amp;lt;12 (n = 10), overlap syndromes (n = 8), patients with infection (n = 11). Mean age of the patients was 27.6±8.9 years. Mean duration of hospitalization was 8±4 days. 12 patients died in hospital and 58 survived. Mean days to death was 5±1 days. Mean SLEDAI (23.6±6.1, 18±5.6 p = 0.05), mean dsDNA (3.1±2.1, 1.7±1.8 p = 0.05) and mean serum IFNα levels in pg/ml (318.8±190.1, 39.9±74.7 p = &amp;lt;0.001) was higher in non-survivors than survivors. On applying binomial logistic regression, serum interferon alpha predicted in-hospital mortality (p = &amp;lt;0.001) while dsDNA(p = 0.4) and SLEDAI (p = 0.5) did not. Area under curve for predicting death was 0.9 for IFNα,0.74 for SLEDAI and 0.7 for dsDNA. A serum interferon alpha level of 140 pg/ml was the best predictor of in-hospital mortality with sensitivity of 84 %and specificity of 94%. Conclusion In-hospital mortality in patients with high disease activity is 17%. dsDNA, SLEDAI and serum interferon levels are predictors of in-hospital mortality. Among these serum IFNα is the best predictor of in-hospital mortality. Disclosure K. yerram: None. P. Devarasetti: None. L. Rajasekhar: None.

Competitive binding of transcription factors underlies flexibility of T peripheral helper cells and T follicular helper cells in SLE.

Peripheral helper T (Tph) cells interact with B cells and promote immune responses at sites of ectopic lymphoid structures (ELSs). To assess the characteristics of Tph cells, we investigated the phenotype of T helper (Th) cells in patients with SLE and the underlying competitive binding mechanisms using cytokine-mediated signal transducer and activator of transcription (STAT) factors. Peripheral blood mononuclear cells from SLE patients and healthy controls were analysed for phenotypic identification. Serum cytokine levels were detected using Luminex assays. In vitro culture was performed to assess cytokine-induced conversion of phenotypes and transcriptional regulation using flow cytometry and PCR. Chromatin immunoprecipitation was used to evaluate STAT binding and histone modifications. CXCR5-PD-1+Tph-like cells were increased in SLE patients and showed strong association with disease activity and renal involvement. Serum IFN-α levels were increased and associated with Tph frequency. IFN-α promoted the differentiation of IL-10-producing CXCR5-PD-1+Tph-like cells, increased the responsiveness of IL-2 and induced the conversion of Tfh-like cells to Tph-like cells. STAT5 gained a competitive advantage and bound to the BCL6 locus at the expense of STAT1, accompanied by suppression of H3K4me3. Finally, anti-IFNAR1 decreased the differentiation of Tph-like cells, thereby suppressing the generation of CD38highCD27highplasmablasts. Tph cells might be crucial makers to effectively reflect disease activity level in SLE patients. The finding that synergy of IFN-α and IL-2 increases Tph cells through competitive transcriptional regulation could be one of the mechanisms responsible for pathological formation of ELSs and helpful for selection of individualized therapeutic approaches for SLE.