Liver fibrosis is known as a condition characterized by chronic inflammation and excessive extracellular matrix deposition that causes cirrhosis and liver failure. Stem cell therapy is a promising strategy for the management of liver fibrosis because it not only improves tissue regeneration but also modulates by immunomodulatory mechanisms.
This systematic review aimed to evaluate the immunoregulatory effects of stem cells in both experimental models and clinical studies of liver fibrosis. A total of 29 studies were included, comprising several stem cell sources, including bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord-derived MSCs (UC-MSCs), adipose tissue-derived MSCs (AT-MSCs), and stem cells from human exfoliated deciduous teeth (SHED), among others. Studies reported that stem cells could decrease proinflammatory cytokines (e.g., TNF-α, IFN-γ, IL-17) and fibrosis-related markers, while increasing levels of antiinflammatory cytokines (e.g., IL-10, IL-4) and regulatory immune cells such as Tregs (regulatory T cells). Stem cells could affect immune homeostasis via modulating in macrophage polarization, T cell subsets, and B cell activity, resulting in attenuated fibrotic progression and improved liver function.
Despite variability in cell types, routes of administration, and fibrosis models, the results support the potential of stem cell therapy to reform the hepatic immune microenvironment. However, more standardized protocols and clinical validations are required.
This study emphasizes the immunomodulatory potential of stem cells as a therapeutic method in liver fibrosis. It brings a clear view into their mechanisms of action and the foundation for future translational applications. 

Spinal cord injuries (SCI) lead to complex primary and secondary damage that disrupts neural function. Current treatments are often insufficient and unable to fully repair spinal cord injuries, highlighting the urgent need for new medicines and innovative therapies.
This study aimed to evaluate the therapeutic potential of abscisic acid (ABA) in SCI by examining its effects on immune-inflammatory genes’ expression in rats. This phytohormone possesses anti-inflammatory and neuroprotective properties, rendering it a potential agent for reducing secondary damage following spinal cord injury. Additionally, we performed protein-protein interaction (PPI), pathway enrichment, functional annotation, and gene ontology (GO) analyses to gain a comprehensive understanding of the functions of the affected genes.
Based on the results, SCI led to changes in the expression of immune/inflammation-related genes in rats. However, the administration of ABA alleviated the effects. ABA downregulated proinflammatory genes (IL-6, IL-1β, MCP, TLR2, TLR4) and neural signaling components (NMDA, AMPA, NK1R), while upregulating adrenergic receptors (ADRA1A, ADRB1) and a gamma-aminobutyric acid receptor (AGBRA2). PPI analysis identified FOS, IL-1β, IL-6, MMP9, and TLR4 as crucial nodes in the network, exhibiting the highest degree of interaction. Functional analyses revealed potential impacts on cellular responses, metabolic processes, and synapse-associated extracellular matrix components. Notably, these genes were enriched in inflammatory signaling pathways according to KEGG analysis.
These findings suggest that ABA has a significant modulatory effect on gene expression following SCI, particularly in reducing inflammation and immune responses, thereby highlighting its potential as a novel therapeutic agent for SCI.

MicroRNA (miR)-425-5p is used as a molecular biomarker to identify cervical cancer (CxCa). However, few studies have examined the miR-425-5p-based modulation of the vital activities of CxCa cells.
The levels of neural cell adhesion molecule 1 (NCAM1) and miR-425-5p in CxCa tissues and cells were tested using western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) tests. CxCa cells’ malignant phenotype was examined through clone formation tests, and transwell tests. CD8+T cells were co-cultured with CxCa cells and then analyzed for apoptosis rates and the expression of activation proteins (granzyme B (GZMB) and perforin) as well as immune factors (tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)) using flow cytometry, western blot, and enzyme-linked immunosorbent assay (ELISA) methods. Finally, in nude mouse experiments, the tumor size was measured for subcutaneous tumors, and the expression of CD8+T cell-related factors was detected.
The NCAM1 and miR-425-5p were down-regulated and up-regulated in CxCa tissue and cells, respectively. After silencing miR-425-5p, CxCa cells showed attenuation in vitality, clone formation rate, and their capacities to migrate, penetrate, and evade immune responses. NCAM1 was targeted and silenced by miR-425-5p. When NCAM1 was silenced, it partially counteracted miR-425-5p’s inhibitory effects on the immune escape and proliferation. In nude mice, the tumor size and weight decreased after silencing miR-425-5p, and levels of CD8, IFN-γ, TNF-α, perforin, and GZMB were elevated. However, these changes were reversed when NCAM1 was silenced.
In conclusion, miR-425-5p mediates the biological behavior and immune evasion of CxCa cells by regulating NCAM1.

Premature infants with immature gastrointestinal tracts rely on parenteral nutrition (PN) to meet nutritional and energy requirements for growth. In this study, we compared the nutrition-related immune status of premature infants receiving SMOF emulsions (multiple oil-fat emulsions) versus those receiving MCT/LCT emulsions (medium-/long-chain triglyceride emulsions) at different times during PN, and we analyzed the relationship between immune function and clinical outcomes.
Sixty premature infants from Dongxihu District People’s Hospital, recruited between September 2023 and September 2024, were divided into an observation group and a control group. The observation group received SMOF emulsions, while the control group received MCT/LCT-containing emulsions. We compared immune function, clinical outcomes, and complications between the two groups at different PN timings. The effects of fat-emulsion type on immune indices and their relationship with clinical outcomes were assessed using logistic regression and ROC analysis.
The clinical data of the preterm infants in both groups were similar. Immune function and clinical outcomes were better in the observation group than in the control group, and the complication rate was lower. Logistic and ROC analyses revealed that the type of fat emulsion was closely related to immune indices, and these immune indices were highly correlated with clinical outcomes.
Both interventions improved immunity in preterm infants, with better results in the observation group than in the control group. The use of SMOF emulsions was superior to MCT/LCT-containing emulsions in preterm infants requiring long-term PN, and this immune improvement significantly optimizes clinical outcomes.

This study aims to investigate the role of notopterol in alleviating endometritis induced by lipopolysaccharide (LPS) and to explore its underlying mechanisms.Human endometrial epithelial cells (hEECs) were treated with LPS to establish an in vitro model of endometritis, and the cells were divided into five groups: control, LPS, LPS+notopterol(15 mol/L), LPS+notopterol(305 mol/L) and LPS+notopterol(45 mol/L) groups. The expression levels of inflammatory factors were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). Apoptosis was detected by TdT-mediated dUTP Nick-End Labeling (TUNEL) method. Cell viability was determined by Cell Counting Kit-8 (CCK-8) test. Western blot was used to detect the expression levels of nuclear factor κB(NF-κB) p65, NF-κB inhibitor (IκBα), p-NF-κB p65 and p-IκBα.
Following LPS treatment, cytokine levels significantly increased compared to the control group.; moreover, cell proliferation decreased, apoptosis increased, and the expression level of p-NF-κB p65 was increased. Subsequently, the LPS-treated hEECs were exposed to notopterygium. Compared to the LPS group.
Treatment with LPS + notopterol resulted in a dose-dependent reduction in inflammatory cytokines, increased cell proliferation, and a significant reduction in apoptosis. Furthermore, the expression levels of p-NF-κB p65 and p-IκBα were downregulated.
These findings suggest that notopterol alleviates LPS-induced endometritis by inhibiting the TLR4/NF-κB signaling pathway.

Adenovirus infection is a common cause of pediatric respiratory disease, often misdiagnosed as a bacterial infection. This study compared immune-inflammatory markers in children with adenovirus- vs bacterial-induced suppurative tonsillitis and evaluated their correlation with adenovirus pneumonia.
A retrospective study of 275 children (145 with adenovirus, 130 with bacterial infections) admitted to The First People’s Hospital of Changde, China (January–June 2019), was conducted. Laboratory markers (white blood cell [WBC] count, C-reactive protein [CRP], serum amyloid A [SAA], procalcitonin [PCT], heparin-binding protein [HBP], tumor necrosis factor-alpha [TNF-α], and interleukin 6 [IL-6]) were analyzed. Adenovirus cases were stratified by pneumonia status (58 with pneumonia, 87 without pneumonia) via chest computed tomography.
Compared with the bacterial group, the adenovirus group had lower WBC counts (14.97 [1.37] vs 18.86 [2.65] ×10⁹/L), CRP levels (15.26 [3.44] vs 26.36 [3.18] mg/L), and PCT levels (15.06 [2.12] vs 42.53 [4.58] ng/L) but higher SAA levels (216.75 [39.23] vs 136.55 [28.66] mg/L). Among children with adenovirus, those with pneumonia had elevated SAA (236.39 [38.67] vs 203.65 [33.95] mg/L), HBP (44.30 [8.93] vs 35.62 [6.77] ng/mL), TNF-α (731.52 [99.21] vs 604.21 [95.53] ng/L), and IL-6 (96.86 [17.63] vs 76.55 [15.50] ng/L) levels. A combination of SAA, HBP, TNF-α, and IL-6 predicted pneumonia with an area under the curve of 0.927 (sensitivity, 87.93%; specificity, 88.51%).
SAA, HBP, TNF-α, and IL-6 are strongly associated with adenovirus pneumonia, and their combined measurement improves diagnostic accuracy.

Cow’s milk allergy (CMA) is one of the most prevalent Immunoglobulin E (IgE)-dependent food allergies in children. Currently, the only accepted treatment for food allergy is avoiding the relevant allergen. The purpose of this study is to investigate the immunological changes following the consumption of heated cow's milk products compared to the usual method of oral desensitization in children aged over two years old with cow's milk allergy.
In a prospective double-blind clinical trial study, 25 children aged two years and older with a definite diagnosis of IgE-dependent cow's milk allergy referred to the allergy clinic of the Children's Medical Center from 2016 to 2017 were enrolled. The eligible patients were randomly divided into two groups: the first group was desensitized with raw milk (normal desensitization: n=13), and the second group was desensitized with heated cow's milk products (intervention group, n=12).
The mean ages in the raw milk group and heated milk group were 3.92±1.44 and 4.50±1.73 years, respectively. The rate of anaphylaxis in the heated milk group was higher than in the raw milk group (50% vs. 15.4%), although the incidence of urticaria and angioedema was not significantly different between the two groups. The mean concentration of serum IgE in the two groups decreased after desensitization compared to before, although there was no significant difference between the two groups. The increase in the number of CD4+Foxp3+ and CD4+ CD25+ cells was less in the heated milk group than the raw milk group, but this difference was not statistically significant. Additionally, the number of eosinophil cells was higher in the heated milk group than in the raw milk group, but this difference was not statistically significant difference.
We concluded that the changes in the level of eosinophil, IgE, and regulatory T cells in the conventional desensitization group were not significantly different compared to desensitization with heated milk. Further multicenter studies with a higher sample size are recommended to confirm these results.

The objective of this study was to compare the concentrations of relative and absolute regulatory T cells (Tregs) in preterm neonates diagnosed with necrotizing enterocolitis (NEC) with those in the control group.
The study consisted of 60 preterm neonates, 30 with NEC and 30 without NEC. Blood samples were obtained and processed for the enumeration of Treg cells by multiparameter flow cytometry with markers such as CD4, CD25, and FOXP3, and the activation markers CD45RA, CD45RO, HLA-DR, and CTLA-4.
There were no significant differences in gestational age, body weight, Apgar score, delivery mode, or incidence of maternal infection between the NEC group and the control group. The relative Treg percentage (% of CD4⁺ T cells) in the NEC group was 7.5 ± 1.2%, which was significantly lower than that in the control group (9.8 ± 1.5%). Compared with that in the control group, the absolute Treg count in the NEC group showed the same trend, and the total CD4⁺ T-cell count decreased significantly. The percentage of naive Tregs (% of Tregs) was significantly higher, whereas those of memory Tregs (% of Tregs), Ki-67+ (% of Tregs), and CD39⁺ (% of Tregs) cells were significantly lower. Tregs may be activated more as the severity of NEC increases, and the elevated levels of interleukin (IL)-10 in NEC may reflect attempts at an effective anti-inflammatory response to the proinflammatory effects of IL-6 and TNF-ɑ.
Treg pathways may hold promise for NEC prognosis, although additional samples should be evaluated to validate these results.

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Natural killer (NK) cells contribute to the development of Rheumatoid Arthritis (RA). Increased expression of programmed cell death protein 1 (PD-1), encoded by the PDCD1 gene, indicates NK cell exhaustion, a process that may be influenced by microRNAs (miRNAs). In this study, we examined PD-1 expression on NK cells from RA patients and evaluated whether miRNAs modulate this pathway.
Although antibiotics are critical for treating infections, they can provoke harmful immune responses by releasing bacterial components that overstimulate the immune system. Such responses may lead to excessive inflammation or cytokine storms. To address this risk, we assessed the immune safety of a newly designed chimeric endolysin, ZAM-MSC, and compared its effects with traditional antibiotics using transcriptomic, proteomic, and computational analyses.
We analyzed public gene and protein expression datasets from antibiotic-treated human cells and performed in silico studies on ZAM-MSC. Differential expression analysis and pathway enrichment were conducted, alongside structural modeling of the endolysin and its predicted interactions with immune receptors.
Antibiotic treatment strongly activated inflammatory genes and pathways, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). In contrast, ZAM-MSC minimally affected immune-related gene expression, with downregulation of interleukin-6 receptor (IL6R) and tumor necrosis factor receptor 1A (TNFRSF1A). Structural modeling showed weak interactions with Toll-like receptors, and epitope analysis predicted low immunogenicity. These results suggest ZAM-MSC may offer a safer antimicrobial alternative, though all protein-level findings are based on computational predictions and require experimental validation. 

Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with a poor prognosis, characterized by immune cell activation. The role of T helper (Th) cell transcription factors in IPF pathogenesis remains unclear. In this study, we investigated Th cell transcription factors and related cytokines in IPF patients.
Twelve IPF patients and eight healthy controls (HC) were enrolled in this pilot study. Serum levels of fibrosis-associated mediators (Interferon-inducible protein 10 (IP-10), tumor necrosis factor-α (TNF-α), tumor growth factor-β (TGF-β), CXCL-8, interferon-γ (IFN-γ)) were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assessed Th transcription factors T box transcription factor (T-bet,), GATA-binding protein 3 (GATA-3), Retinoic acid-related orphan recepto (ROR-γt), forkhead box P3 (FOXP3)) and intracellular cytokines (IL-4, IL-17).
SerumTGF-β, CXCL-8, TNF-α, and IFN-γ were significantly elevated, while IP-10 (pT-bet, GATA3, ROR-γt, or FOXP3 were observed. Positive correlations were found between T-bet and GATA3, IL-4, ROR-γt, and TNF-α expression with age, while FOXP3 expression negatively correlated with age.
T-cell transcription factors were unchanged in IPF despite changes in inflammatory protein expression. Reduced IP-10 may serve as a potential marker.

Lipopolysaccharide (LPS)–induced inflammation in macrophages involves complex signaling pathways. This investigation explored the regulatory roles of triggering receptor expressed on myeloid cells-1 (TREM1) and interleukin (IL)-26 in the Janus kinase/signal transducer and activator of transcription (JAK/STAT) and nuclear factor-kappa B (NF-κB) p65 pathways in LPS-stimulated RAW 264.7 macrophages.

RAW 264.7 cells were treated with LPS to assess TREM1 expression. TREM1 or IL-26 was silenced using short hairpin RNA (shRNA), while IL-26 was overexpressed via plasmid transfection. The JAK2 inhibitor AG490 was used to block JAK/STAT signaling. Western blot, reverse transcription–quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were employed to analyze the protein and mRNA levels of inflammatory markers and signaling molecules.
Results showed that LPS upregulated TREM1 expression. In addition, TREM1 knockdown suppressed p65 activation and reduced inflammatory cytokine levels. Moreover, silencing TREM1 inhibited IL-26 and JAK/STAT phosphorylation (p-JAK1, p-JAK2, p-STAT1, and p-STAT3). Similarly, IL-26 knockdown or AG490 treatment attenuated p65 activation and inflammation. Furthermore, IL-26 overexpression reversed the anti-inflammatory effects of TREM1 silencing.
Overall, TREM1 promoted LPS-induced macrophage inflammation via IL-26–mediated JAK/STAT and NF-κB pathway activation, suggesting that TREM1 and IL-26 are potential therapeutic targets.

The risks associated with in vivo tests in the diagnosis of immediate drug hypersensitivities result in evaluating alternative in vitro tests, such as the Basophil Activation Test (BAT). This pilot study aimed to set up a BAT and compare it with a specific Immunoglobulin E (sIgE) assay for penicillin G and Ibuprofen in patients with immediate hypersensitivity to β-lactams or nonsteroidal anti-inflammatory drugs (NSAIDs).
Eleven subjects with a clear history of immediate hypersensitivity to one of the β-lactams (n=5), the NSAIDs (n=3), or both (n=3) entered this study. BAT and sIgE assays were performed regarding the patient’s history.
The most frequent manifestations were angioedema, shortness of breath, urticaria, and nausea. Eight patients had anaphylactic reactions. The results presented a positive BAT for penicillin G and one for Ibuprofen. Moreover, three patients with a history of the β-lactams reaction demonstrated positive sIgE to β-lactams in the ImmunoCAP. Despite a lack of agreement between the positive results of the BAT and sIgE assay, five patients were identified by one of these methods.
Despite positive BAT and sIgE results in two and three patients, respectively, the risks, high cost, and time-consuming nature of drug challenges render these tests valuable for reducing the number of patients who are candidates for a drug challenge.

Predominantly a widespread beta herpesvirus, human cytomegalovirus (HCMV) triggers lifelong latent infection in most of the people, and HCMV vaccine development has been designated a high public health priority.
In the current study, the in vitro safety profile and potential immunotoxic effects of a novel messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccine designed against human cytomegalovirus (HCMV) were assessed. The aim was to measure inflammation, allergic reactions, complement activation, cytotoxicity, and hemolytic effects of the mRNA-LNP vaccine. Proinflammatory cytokine secretion, evident in human peripheral blood mononuclear cells (hPBMCs) treated with unmodified mRNA-LNP, was markedly attenuated by incorporating modified nucleotides.
The vaccine appeared incapable of sparking allergic cytokine production or complement activation. Cell viability assays indicated no pronounced cytotoxicity, and hemolysis assays showed no notable hemolytic activity.
The findings suggest that the modified mRNA-LNP vaccine exhibits a promising in vitro safety profile, supporting further development of this vaccine candidate.

Liver fibrosis is a significant global health issue characterized by an abnormal accumulation of extracellular matrix proteins, that disrupts normal liver architecture and function. Mesenchymal stem cells (MSCs) show therapeutic potential by releasing extracellular vesicles (EVs) containing regulatory microRNAs like miR-10a.
This study evaluates miR-10a-enriched human umbilical cord MSC (hUCMSC)-EVs in a CCl₄-induced model of liver fibrosis, focusing on inflammatory marker modulation. Liver fibrosis was induced in experimental animals using CCl₄ administration. MSCs were isolated from the human umbilical cord and loaded with either a miR-10a mimic or a control sequence through Lipofectamine 3000. EVs were then isolated from the culture media of both miR-control and miR-10a-modified MSCs. The therapeutic potential of these miR-10a-loaded EVs was assessed by treating the CCl₄-induced fibrosis model with these vesicles. The efficacy of the treatment was evaluated by measuring two anti-inflammatory markers interleukin (IL)-10 and IL-4) and three pro-inflammatory markers (tumor necrosis factor-α (TNF-α), IL-6, and interferon-γ (IFN-γ)) using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) techniques.
The administration of miR-10a-loaded MSC-EVs resulted in a significant modulation of inflammatory markers. Our results revealed an increase in the levels of anti-inflammatory cytokines (IL-10 and IL-4) and a concurrent decrease in pro-inflammatory cytokines (TNF-α, IL-6, and IFN-γ) in the treated group compared to the control group.
The study demonstrates the therapeutic potential of MSC-EVs encapsulating miR-10a in ameliorating CCl₄-induced liver fibrosis. By modulating the balance between pro-inflammatory and anti-inflammatory cytokines, miR-10a-loaded EVs show promise as a targeted treatment approach for liver fibrosis.

  The autosomal recessive form of hyperimmunoglobulin E syndrome (AR-HIES), caused by mutations in the DOCK8 (Dedicator of Cytokinesis 8) gene, presents a wide range of clinical manifestations and phenotypically overlaps with several types of combined immunodeficiency disorders characterized by elevated serum IgE levels. Due to the high rates of morbidity and mortality, as well as the potential curability through hematopoietic stem cell transplantation (HSCT), early and accurate differential diagnosis of this syndrome is crucial for optimal management and improved prognosis. Flow cytometry tests can be beneficial for early diagnosis of many inborn errors of immunity (IEIs), including this syndrome. This study, conducted for the first time on Iranian patients, investigated the expression of the DOCK8 protein.
DOCK8 expression was assessed by flow cytometry in 14 patients (6 males and 8 females) with a clinical diagnosis of DOCK8 deficiency. The diagnosis was ultimately confirmed through genetic testing.
The results showed that DOCK8 expression in patients was significantly lower compared to the healthy control group.
Flow cytometric evaluation of DOCK8 protein expression offers a rapid and efficient
diagnostic method with a sensitive detection range suitable for many cases. This approach can facilitate the diagnosis of DOCK8 deficiency, thereby enabling timely and effective disease management. 

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by excessive extracellular matrix (ECM) deposition, largely mediated by activated fibroblasts. Epithelial-mesenchymal transition (EMT), regulated by transcription factors such as TGF-β, Twist1, and Snail, is a critical mechanism in fibrosis progression. AMP-activated protein kinase (AMPK) has been implicated in modulating fibrotic pathways, but its role in EMT remains unclear. This study aimed to explore the interaction between EMT and AMPK signaling in pulmonary fibrosis.
A bleomycin-induced pulmonary fibrosis mouse model was used. Histological analysis assessed fibrosis and inflammation, while gene expression (TGF-β, Twist1, Snail) was measured by qPCR. Protein levels of E-cadherin, α-SMA, and phosphorylated AMPK were analyzed using Western blotting to evaluate EMT and AMPK activity.
Bleomycin-treated mice showed significant lung inflammation and fibrosis, particularly in the lower region of the left lung. Gene expression analysis revealed elevated TGF-β, Twist1, and Snail in fibrotic areas. Protein analysis demonstrated increased α-SMA and decreased E-cadherin, confirming EMT induction. Notably, AMPK phosphorylation was significantly reduced in fibrotic regions, occurring concurrently with EMT activation.
These findings indicate an inverse relationship between AMPK signaling and EMT in pulmonary fibrosis. EMT may serve as a direct therapeutic target, either by inhibiting transcription factors such as Snail and Twist1 or by modulating upstream metabolic regulators including AMPK.

We aimed to investigate the causal relationship between cardiovascular-related proteins and osteoporosis and to assess the influence of immune cell traits and lifestyle factors such as smoking and alcohol consumption on osteoporosis risk.
A two-sample Mendelian randomization (MR) approach was employed using publicly available genome-wide association study (GWAS) data. Univariable and multivariable MR analyses were conducted using the inverse variance weighted (IVW) method to evaluate causal effects. Additional sensitivity analyses were performed to validate findings.
Three cardiovascular proteins showed significant associations with osteoporosis and pathological fractures: TNF-related apoptosis-inducing ligand receptor 2 (OR=0.10), TNF-related activation-induced cytokine (OR=2.90), and C-C motif chemokine 4 (OR=1.12). Lifestyle factors, including household tobacco smoke exposure, daily smoking quantity, and alcohol consumption, were also significantly associated with increased osteoporosis risk. Immune cell traits were identified as potential mediators in the relationship between cardiovascular proteins and osteoporosis.
This study highlights a novel link between cardiovascular health and osteoporosis, suggesting that specific proteins increase risk, while immune traits mediate this effect, and lifestyle factors are independent risk factors. These findings underscore the importance of integrated strategies addressing inflammation and lifestyle in osteoporosis prevention and management.

Component- Resolved Diagnosis (CRD) is an effective tool in allergy diagnosis, that detects specific IgE to allergenic molecules. The ALEX (Allergy Explorer) test, commercially available since 2019, measures specific IgE to allergenic extracts and components associated with inhalant, food, animal, latex, and insect allergens. CRD results should be interpreted based on the patient's clinical history.
Since Children's Medical Center Hospital is one of the largest referral centers for allergic patients, we evaluated the results of the ALEX2 test in patients referred to this center and compared them with the patients’ clinical symptoms.
Clinical symptoms were concordant with positive CRD (ALEX2) test in 76.7% of cases. The overall agreement between positive allergen components and clinical symptoms was 58%.
These findings indicate that the ALEX2 test can improve diagnostic accuracy in allergic patients; however, positive test results should be interpreted in the context of the patient’s clinical history.

Adenosine deaminase 2 (ADA2) deficiency is an autosomal recessive disease with varying degrees of clinical phenotypes and disease severity. The phenotypic spectrum of the disorder has expanded from vasculitis with stroke to include pure red cell aplasia, bone marrow failure, autoimmune cytopenia, lymphoproliferation, and variable degrees of immunodeficiency.
Here, we describe two cases of ADA2 deficiency: one presented with an early-onset stroke that resembled an early-onset polyarteritis nodosa (PAN), and the other as an adult-onset vasculitis that progressed to severe neutropenia with recurrent infection and lymphoproliferation. Patient 1, a 10-year-old male, had a reported pathogenic ADA2 homozygote variant; c.139G˃C (p.Gly47Arg), and patient 2, a 34-year-old male, had a reported likely pathogenic homozygous ADA2 variant; c.578C>T (p.Pro193Lys).
Our second patient was the first DADA2 patient who showed that DADA2 is not a static disease and can progress from vasculitis to bone marrow failure in the course of the disease. Therefore, the previous recommendation introducing anti–TNF-α as a preferred treatment for vasculitis manifestations and hematopoietic stem cell transplantation as the preferred treatment for bone marrow failure can no longer apply. We should consider HSCT for DADA2 patients from the very beginning.
The Physician has to be aware of this monogenic disorder's varied presentation and multi-organ involvement. Early recognition and proper treatment are crucial for this potentially fatal disease.

Common variable immunodeficiency disorder (CVID) is the most prevalent primary immunodeficiency in adults. Pathogenic mutations of the TNFRSF13B gene were identified in CVID patients and associated with autoimmunity and lymphoproliferation. A study on Swedish children unaffected by CVID has shown that rare variants in the TNFRSF13B gene increase the risk of asthma. To the best of our knowledge, asthma has not been reported in CVID patients with TNFRSF13B gene mutations. We described a patient suffering from asthma and CVID with a heterozygous mutation in the TNFRSF13B gene. According to our findings and previous studies, mutations in the TNFRSF13B gene seem to be possibly associated with the occurrence of asthma in CVID patients.