Background and Aim Chronic Lymphocytic Leukemia (CLL) is the most commonly occurring leukemia in adults, accounting for about 30-25% of total leukemia. One of the important etiological causes of this leukemia is the disruption of the Nuclear Factor Kappa B (NF-kB) signaling pathway. The two proteins of Apoptosis-Inducing Ligand (APRIL) and B-Cell Activating Factor (BAFF) play a role in the pathogenesis of this leukemia by affecting the NF-kB signaling pathway. In this study, due to the effect of miRNAs in regulating many cellular processes, the prediction of the prominent miRNAs targeting APRIL and BAFF transcripts in B-cell CLL patients was evaluated using specific and different bioinformatics programs. Methods & Materials Afterwards retrieving the sequences of APRIL and BAFF proteins from the NCBI website, by using several programs including miRanda, TargetScan, miRWalk, DIANA and miRDB with different algorithms, the prediction of miRNAs targeting these genes was investigated. Ethical Considerations This study was approved by the Research Ethics Committee of Arak University of Medical Sciences. Results Based on the scoring system of bioinformatics programs, “ hsa-miR-145-5p” and “ hsa-miR-185-5p” were identified as miRNAs targeting APRIL gene, while “ hsa-miR-424” and “ hsa-miR-497” were miRNAs targeting BAFF gene. They were suggested for the practical studies in future. Conclusion Based on the important role of APRIL and BAFF genes in the normal process of cell death and B-cell evolution, it seems that the mi-RNAs predicted by bioinformatics programs using different algorithms can be used as a diagnostic molecular biomarker to identify B-cell CLL patients.

Background: Pemphigus vulgaris, the most common form of pemphigus, is due to the production of auto-antibodies directed against adhesion molecules (desmoglein 1 and 3) that belong to the cadherin family. B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) may play a significant role in autoimmune diseases such as pemphigus vulgaris. Only a few studies have been done on the level of APRIL and BAFF in PV patients but none have investigated both levels; therefore, determination of both proliferation inducing ligands (BAFF and APRIL) in pemphigus vulgaris is of significant importance and was considered as the goal of the present study.Methods: This analysis included 22 patients with PV and 22 sex and age matched healthy controls. None of the patients had previously been treated with corticosteroids or any immunosuppressive drugs in the previous three months. The BAFF and APRIL levels were evaluated in patient and control groups by use of ELISA method.Results: Comparison of the serum levels of BAFF and APRIL between patients and controls was done using Mann-Whitney U test. The BAFF levels in our 22 patients and control sera were undetectable. On the other hand, concentrations of APRIL in 22 cases were 2.09±4.94 and 0.85±2.01 in the control group.Conclusion: BAFF levels were undetectable in cases and the difference in APRIL levels between patient and control groups was not significant (p=0.28). So, it can be concluded that although BAFF and APRIL may play a role in autoimmune diseases, their role in pemphigus vulgaris is doubtable.

Background and Aim: B-cell activating factor (BAFF) belongs to the tumor necrosis factor (TNF) superfamily and plays a critical role in B-cell survival and differentiation. Overexpression of BAFF has been linked to autoimmune diseases and B-cell malignancies. The biologically active segment of this protein is a soluble domain, making it a promising target for antibody-based therapies. This study aimed to develop a polyclonal camel antibody capable of detecting BAFF on cell surfaces. Methods: An expression vector, pET22b, containing the extracellular domain of the BAFF protein (NM_001145645.2), was constructed and introduced into Escherichia coli BL21 (DE3) using the calcium chloride heat shock method (CaCl2). Subsequently, the recombinant protein was induced using 1mM IPTG and protein purification was carried out with Ni2+–NTA resin. A 9-month-old female Camelus dromedaries was immunized with purified recombinant BAFF protein (rBAFF) mixed with Freund's adjuvant. Following immunization, the isolated polyclonal antibody was assessed using ELISA, western blotting, and flow cytometry to detect rBAFF protein. Results: The study confirmed the successful preparation of recombinant BAFF protein and the effectiveness of camel immunization and purification processes. The isolated polyclonal antibody demonstrated the ability to identify recombinant BAFF proteins in ELISA and western blot tests. Flow cytometry demonstrated its capacity to detect BAFF protein on cell surfaces. Conclusion: Given the significance of diagnosing and developing novel adjuvant treatment methods for autoimmune diseases and cancer, this study's findings support the potential use of polyclonal antibodies targeting the BAFF antigen as valuable tools for these purposes.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by a complex immune response. Because of the complex nature of MS pathogenesis, a panel of biomarkers derived from different platforms will be required to reflect disease-related alterations. Monitoring and evaluation of molecules associated with the pathogenesis of the disease would provide useful information on disease progression and therapeutic assessment. In view of this, we evaluated the mRNA expression levels of B-cell activating factor (BAFF), high mobility group box 1 (HMGB-1), Toll like receptor (TLR) 4 and TLR7 in MS. These molecules are implicated in the pathogenesis of MS; however, they have received little attention. PBMCs were isolated from whole blood of 84 relapsing remitting multiple sclerosis patients and 70 healthy controls. Relative quantitative RT-PCR was applied to quantify the transcriptional levels of the immune markers. The mRNA expression levels of TLR7 were significantly elevated in RRMS patients than healthy controls. TLR4 expression was found to be significantly lower in the patients than control group. We found no difference analyzing the mRNA levels of BAFF and HMGB1. Our data highlights the immune marker correlates in RRMS patients. However, further in-depth studies are warranted to check the role and the relevance of these immune markers in autoimmune diseases such as MS.

The pathogenic roles of Interleukine-16 (IL-16), CCL27, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and B-cell activating factor (BAFF) has been shown in some autoimmune and inflammatory diseases. We aimed to correlate the circulatory changes of such factors with the severity of disease in patients with multiple sclerosis (MS). This case-control study was conducted on 84 MS patients and 83 healthy controls. We measured the serum levels of IL-16, CCL27, TRAIL, and BAFF in all participants by enzyme-linked immune sorbent assay. Using the expanded disability status scale (EDSS), we evaluated the severity of MS. Finally, we assessed the correlation between serum levels of such factors with the severity of MS. We found increased serum levels of CCL27, IL-16, and BAFF in patients with MS compared to those in healthy subjects. However, no difference was found in serum levels of TRAIL between the patients and controls. In addition, a significant positive correlation between serum levels of CCL27, IL-16, TRAIL, and BAFF with disease severity according to EDSS score was determined. We showed higher serum levels of CCL27, BAFF, TRAIL, and IL-16 in MS patients with more severe disabilities than mild forms. Such finding may represent their contribution to the pathogenesis of MS. Blocking such molecules may yield new treatments for MS.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a potential trigger for central nervous system (CNS) autoimmune disorders. The most common type of spinal cord pathology following novel coronavirus infection is immune-mediated/autoimmune transverse myelitis (TM); however, there are also rare forms of spinal cord pathology ‒ tract-specific myelitis ‒ previously considered as non-autoimmune-originated.Methods: The current study includes case series of 5 patients with a rare type of myelitis with predominant involvement of the dorsal and lateral columns following coronavirus disease 2019 (COVID-19). We aimed to analyze cytokines parameters in cerebrospinal fluid (CSF) of affected patients. In order to support the autoimmune origin of the disease, CSF cytokine profiles were compared to patients with TM following COVID-19 (n = 12). Scale variables were compared between two independent groups using t-test or Wilcoxon-Mann-Whitney test depending on the distribution.Results: In contrast to patients with TM, patients with tract-specific myelitis demonstrated higher levels of a proliferation-inducing ligand (APRIL), B cell activating factor (BAFF), interleukin (IL)-11, and thymic stromal lymphopoietin (TSLP). The BAFF/APRIL system is renowned for its involvement in the genesis and advancement of autoimmune disorders, and its pronounced increase in this case supports the autoimmune origin of the disease.Conclusion: The heightened activation of BAFF and APRIL cytokines, which promote B-cell maturation, suggests an autoimmune origin of tract-specific myelitis, thereby informing prognosis and treatment strategies for affected patients.

Introduction. To evaluate the impact of TACI fusion protein (TACI-Ig) on IgA nephropathy (IgAN) in rats, and to explore its mechanism and relationship with TLR4/MyD88/NF-κB pathway. Method. Sprague Dawley(SD)rats were divided into six groups: control, model, TACI-Ig low dose (TACI-Ig-L), medium dose (TACI-Ig-M), high dose (TACI-Ig-H), and prednisone acetate (PAT) group. The control group and model group received physiological saline injections, while the TACI-Ig groups were administered doses of 7.18, 14.36, and 28.72 mg/kg of TACI-Ig, respectively. PAT group was pretreated with prednisone acetate. After 8 weeks, kidney weight/body weight ratios, 24-hour urine protein (24 h UP), serum creatinine (SCr), and blood urea nitrogen (BUN) levels were measured. Additionally, concentrations of B cell activating factor (BAFF), APRIL, and Gd-IgA1 were evaluated by using ELISA. Pathological changes in kidney tissues were scored, and TLR4, MyD88, NF-κB expression levels were detected through western blot (WB) and RT-qPCR. Results. Renal function assessments showed that the IgAN model group exhibited increased in 24 h UP, SCr, BUN, and elevated serum levels of BAFF, APRIL, Gd-IgA1, alongside higher TLR4/MyD88/NF-κB protein expression. TACI-Ig treatment significantly reduced proteinuria, SCr, BUN, levels of BAFF, APRIL, and Gd-IgA1 in IgAN rats. Pathologically, TACI-Ig ameliorated glomerular mesangial deposition and fibrosis. It also inhibited TLR4/MyD88/NF-κB protein expression, demonstrating anti-inflammatory and immune regulatory effects. Conclusions. TACI-Ig mitigates renal injury in IgAN rats by reducing inflammatory infiltration and IgA deposition and suppressing the pathway of TLR4/MyD88/NF-κB, offering data for developing effective treatments for IgAN.

Utilizing subunit vaccines is one of the strategies to address influenza infection. Recent innovations have focused on high doses of vaccine antigens and immune enhancers or adjuvants to induce more robust and long-lasting immune responses. Here, an effect of the B cell-activating factor receptor (BAFF-R) to increase the magnitude and durability of immune responses of the recombinant HA1 (rHA1) protein against the H1N1 influenza virus was studied. The HA1 protein and the effector domain of BAFF-R were expressed in the pET-28a (+) vector. Eight-week-old BALB/c mice were equally grouped into five groups (n=20). The 15 and 25 μ, g/μ, L of rHA1 were mixed with 2 μ, g/μ, L of rBAFF-R and injected three times for vaccinated groups. Three control groups received normal saline and two concentrations of rHA1. The ability of rBAFF-R in eliciting HA-specific antibody response and stimulating T lymphocyte proliferation to induce the cell-mediated immunity was assayed. Induction of protection was evaluated following the challenge with PR8 strain. Analysis of immune responses showed that the co-administration of rBAFF-R with rHA1 boosted HI responses to the antigen in mice, whilst it was not able to promote the T cell proliferation responses against influenza. Compared to rHA1alone, the rBAFF-R/rHA1 generated efficient protection for the animals. There were no significant differences in eliciting the immune responses in mice immunized with the lower dose of rHA1 than that with the higher dose. The data indicate the rBAFF-R can enhance the primary and memory immune responses to protect against influenza infection.

Background: Producing IL-17, Th17 cells induce BAFF and APRIL, two important mediators for Bcell survival and activation. Common variable immunodeficiency (CVID) is a group of many primary immunodeficiency diseases with a common set of features (including hypo-gammaglobulinemia) and different underlying causes. The prevalence of CVID is 1 to 50, 000. Hence, the aim of this study was to measure IL-17 gene expression in peripheral blood of patients with CVID.Methods: Total mRNA extracted from whole blood samples of 10 patients with CVID and 10 normal controls; then, IL-17 gene was measured using qRT-PCR.Findings: There was a slight decrease in transcript levels of IL-17 in patients with CVID, even though, it was not statistically significant (P=0.195).Conclusion: We showed that IL-17 is decreased in patients with CVID and this could be an explanation for their humoral immunity response insufficiencies. Absence of statistical significance in this IL-17 reduction may be due to our sample size and increasing the number of samples may result in statistical significance of this in future studies.

Introduction: Textile wastewaters are heavily polluted with dyes and chemicals and have a broad range of pH, high COD concentration and suspended particles. In this study, the efficiency of color and turbidity removal from synthetic textile wastewaters were investigated by a combined process of coagulation/ flocculation and electron beam irradiation.Materials and Methods: The experiments have been done on model dye solution samples, which were prepared from ten dyes supplied from Yazd Baff factory. Aluminum sulphate was employed as coagulant. Then samples were irradiated by electron beam accelerator at different doses. Absorption spectra of the samples were measured using UV-Vis spectrophotometer. The pH and turbidity values of the solutions were measured by a pH meter and turbidimeter.Results: According to results, the degree of decoloration and turbidity removal of synthetic dye solutions increased when the alum concentration increased and reached 64% and 90% respectively at 112 ppm of alum. After irradiation, it is observed that absorbance decreased rapidly at 540 nm by increasing the radiation dose because of macromolecules degradation and then it decreased slowly to a degree of decoloration of 95% at 3 kGy. The level of pH decreased by irradiation and then changed very slowly or remained constant with increasing irradiation dose.Conclusion: The results indicate that a combination of coagulation/ flocculation and irradiation is so effective for turbidity removal and decoloration. Coagulation process eliminates suspended particles from disperse dyes effectively, while destruction of soluble dye molecules happens by irradiation, which considerably increases decoloration efficiency.