Immunodeficiency Research Articles

A novel mutation in FNIP1 associated with a syndromic immunodeficiency and cardiomyopathy

AbstractGenetic variants in Folliculin interacting protein 1 (FNIP1) were recently discovered as monogenic causes for immunodeficiency and cardiomyopathy, with only a few patients diagnosed thus far. In this study, we describe a patient harboring a novel genetic variant in FNIP1 causing immunodeficiency with cardiac involvement. Clinical and immunological workups were performed. Genetic evaluation utilizing whole-exome sequencing (WES) and Sanger sequencing was conducted. The index patient (subject II-4) presented with hypertrophic cardiomyopathy, recurrent infections, and chronic diarrhea during infancy. Immune workup revealed agammaglobulinemia and a lack of B lymphocytes. Genetic evaluation identified a homozygous 13-bp duplication variant in FNIP1 (c.52_64dupGCGCCCGGCCGCG, p. Asp22GlyfsTer21) resulting in a frameshift in exon 1/18. She was treated with supplemental intravenous immunoglobulins (IVIg) with good control of sinopulmonary and gastrointestinal manifestations. Her sibling (subject II-1) had similar clinical features, along with dysmorphic facial features and hypotony, and succumbed to cardiogenic shock at the age of 2 months, prior to genetic evaluation. Diagnosis of novel immunodeficiencies promotes our understanding of the immune system, enabling genetic counseling as herein, and may assist in the development of novel medical therapies in the future. FNIP1 loss-of-function should be considered in patients presenting in infancy with cardiac manifestations along with agammaglobulinemia (and B-cell lymphopenia).

KINGELLA KINGAE SEQUENCE TYPE 25 MENINGITIS IN AN IMMUNOCOMPETENT TODDLER: CLINICAL AND MOLECULAR APPROACH.

Kingella kingae is a cause of bacteremia, endocarditis, and the leading cause of osteoarticular infections between 6 and 48 months of life. We report on a rare case of K. kingae meningitis in the absence of endocarditis and immune deficiency in a 26-month-old boy emphasizing the distinct genomic determinants of the strain which may be of importance to the pathogenesis of the disease.

Integration of metabolomics and transcriptomics to reveal anti-immunosuppression mechanism of Lycium barbarum polysaccharide

It is well documented that immunosuppression in chickens increases the risk of secondary infections and immunodeficiencies, resulting in significant financial setbacks for the poultry sector. It is crucial to determine if Lycium barbarum polysaccharide (LBP) can counteract immune suppression in young chickens, considering its known ability to modulate immune responses. The aim of this study was to investigate the antagonistic effect and mechanism of LBP on immunosuppression in chicks. A total of 200 seven-day-old Hyland Brown laying hens were used to develop an immunosuppression model and to investigate the optimal time of use and optimal dosage of LBP. A further 120 seven-day-old Hyland Brown laying hens were used to investigate the mechanism of antagonism of LBP against immunosuppression at the optimal time and dosage. The results demonstrated that LBP significantly elevated body weight, spleen index, and peripheral lymphocyte transformation rate, and ameliorated pathological spleen damage in immunosuppressed chickens. A total of 178 differential genes were significantly upregulated following LBP intervention, with a significant enrichment in immune-related pathways, including the chemokine signalling pathway, the C-type lectin receptor signalling pathway, the B-cell receptor signalling pathway, platelet activation, natural killer cell-mediated cytotoxicity, and Th1 and Th2 cell differentiation. A total of 20 different metabolites were identified by metabolomics, which were mainly involved in vitamin metabolism, lipid metabolism, nucleic acid metabolism and amino acid metabolism. The integrated examination of transcriptomic and metabolomic data revealed that the glycerophospholipid metabolic pathway stands out as the most significant among all metabolic pathways. The results demonstrated that LBP regulate the immune system in a multi-pathway and multi-target way.

Innate immunodeficiencies: a group of primary immunodeficiencies predisposing exclusively to common diseases

Abstract Background Innate immune deficiencies can impair both cellular and humoral immune responses. In contrast, other immune functions may appear normal, leading to increased susceptibility to specific pathogens, such as severe viral infections or Mendelian Susceptibility to Mycobacterial Disease (MSMD). Studying these deficiencies is essential for understanding the pathophysiology of these infectious diseases. Main body While primary immunodeficiencies (PIDs) generally cause vulnerability to multiple infections, innate immunodeficiencies increase susceptibility to specific pathogens, despite normal immune responses to others. Patients with these deficiencies show normal immunoglobulins and lymphocyte subpopulations, complicating diagnosis. This review highlights genetic susceptibility to mycobacteria, pneumococci, herpes simplex virus, and candidiasis, emphasizing recognizing this subset of PIDs. Conclusion This review highlights the diverse spectrum of genetic mutations contributing to defects in innate and intrinsic immunity, including Mendelian susceptibility to mycobacterial disease (MSMD), chronic mucocutaneous candidiasis, and predispositions to invasive bacterial and viral infections. Identifying key mutations in pathprovideh such as TLR3, IFN signaling, and IL-17A/F immunity provides valuable insights into the pathogenesis of these conditions. Our findings underscore the need for early genetic diagnosis and targeted interventions, particularly in regions with high undiagnosed cases, to reduce the morbidity and mortality associated with defects in innate and intrinsic immunity.

Characteristics and eye disease distribution of HIV-infected or AIDS patients: a single-center study

Objective: To explore the characteristics and eye disease distribution of human immunodeficiency virus (HIV)-infected or acquired immune deficiency syndrome (AIDS) patients reported by Beijing Tongren Hospital, Capital Medical University. Methods: A retrospective case series study was conducted. Data of HIV-infected or AIDS patients who were reported for the first time in the Chinese Center for Disease Control and Prevention Information System by Beijing Tongren Hospital, Capital Medical University from January 1, 2012 to December 31, 2021 were collected. Epidemiological data such as the patient's gender and age were recorded, and information such as the patient's clinical diagnosis, department classification, and laboratory test results were retrieved from the hospital's outpatient and emergency system and laboratory information system. Results: A total of 191 HIV-infected or AIDS patients were included, with an average age of (36.71±13.52) years, including 177 males and 14 females. The proportion of male and female patients showed no statistically significant change over the years (P>0.05). Most cases were initially diagnosed in the department of ophthalmology (75 cases, 38.22%), followed by the department of dermatology (49 cases, 25.65%). There were 42 cases (56.00%) reported in the fundus group, 10 cases (13.33%) in the cataract group, 8 cases (10.67%) in the refractive center, and other cases in the glaucoma, cornea, and ocular tumor groups. The ophthalmological diagnoses included uveitis (21 cases, 28.00%), retinopathy (13 cases, 17.33%), cataract (11 cases, 14.67%), refractive error (7 cases, 9.33%), glaucoma (4 cases, 5.33%), retinal detachment (3 cases, 4.00%), vitreous hemorrhage (3 cases, 4.00%), cytomegalovirus retinitis (2 cases, 2.67%), ocular tumor (2 cases, 2.67%), optic neuropathy (2 cases, 2.67%), conjunctivitis (2 cases, 2.67%), keratoconus (1 case, 1.33%), chronic dacryocystitis (1 case, 1.33%), lacrimal duct obstruction (1 case, 1.33%), corneal endothelial decompensation (1 case, 1.33%), and ectropion (1 case, 1.33%). Some patients had co-infections with syphilis, hepatitis B, and hepatitis C. Conclusions: There are undiagnosed HIV-infected or AIDS patients in some departments of non-infectious general hospitals, and the ophthalmological manifestations are mostly uveitis and retinopathy. Ophthalmologists should pay attention to the HIV infection or AIDS infection status of patients with eye diseases such as uveitis and retinopathy to reduce the risk of occupational exposure.

Development of Streptococcus pyogenes pneumnonia and pleural empyema post-chickenpox infection in a 5-year-old child: A case report

Background: The introduction of the varicella vaccine has led to a significant decrease in pediatric varicella-induced invasive Streptococcus pyogenes (group A streptococcal [GAS]) infections. However, the development of a pleural empyema following a chickenpox infection is a rare complication in pediatric patients. Case presentation: In this report, we present a 5-year-old male patient who presented to the emergency department with a deteriorating course two days after a chickenpox infection. The patient complained of high-grade documented fever, a congested throat, abdominal pain, shortness of breath, and most importantly, decreased air entry on the right side of the chest, along with the presence of crepitations. Such a deteriorated clinical picture suggested the presence of an infectious cause. The patient’s physical examination and radiological imaging provided evidence for the presence of lower right-sided lobar pneumonia. On the second day of hospitalization, the patient showed worsening respiratory distress, prompting further investigations that confirmed the development of a right-sided pleural empyema through radiological imaging. Pediatric surgery consultation was requested, and 500 cc of pus was drained following the insertion of a chest tube, which was later sent for analysis. The patient’s clinical picture improved significantly following this intervention. Due to the severity of his condition, the patient was transferred to the pediatric intensive care unit (PICU) for close monitoring. After one night in the PICU, during which his condition stabilized and oxygen therapy was gradually weaned off, the patient continued to improve on the general ward. Daily assessments and laboratory tests showed decreasing inflammatory markers and resolution of symptoms. Following three days of admission and confirmation of no underlying immunologic deficiency, the patient was discharged home with appropriate antibiotic therapy and follow-up instructions. Discussion: Similar cases have been sporadically documented in pediatric literature, with notable examples involving older patients. The pathophysiology involves complex immune interactions and virulence factors of GAS, contributing to severe outcomes such as pleural effusion. Conclusion: In this case, the 5-year-old patient experienced a severe progression from chickenpox to pleural empyema but ultimately improved following prompt medical intervention and chest tube drainage. The patient was discharged after a successful recovery, highlighting the efficacy of early recognition and treatment in managing such complications.

Tetracycline and Oxacillin Act Synergistically on Biofilms and Display Increased Efficacy In Vivo Against Staphylococcus aureus.

Oxacillin (bactericidal) and tetracycline (bacteriostatic) are clinically relevant antibiotics that are routinely prescribed to treat Staphylococcus aureus infections but not conventionally used in combination. There is an urgent need for treatment regimens that can act upon biofilms during infection, associated with chronic infections on indwelling devices, as well as acute planktonic (systemic) infection. Here we show that in an in vitro model oxacillin and tetracycline act synergistically against S. aureus UAMS-1 biofilms, reducing the concentration of both antibiotics necessary to eradicatean established biofilm. Using an in vivo zebrafish larval infection model with S. aureus NewHG, they display improved bacterial clearance compared to each drug alone and can counteract a loss of host phagocytes, an important innate defence against S. aureus. In these cases, the bacteriostatic nature of tetracycline enhances rather than dampens the bactericidal action of oxacillin, although an exact mechanism remains to be elucidated. We suggest a dual therapy could be of clinical use against biofilm-forming S. aureus and has a potential use in patients with a compromised immune system.

Prevalence of Vancomycin-Resistant Enterococcus spp. Isolates in Southeast Iran, Zahedan

Background: Enterococci are clinically significant, especially in individuals with compromised immune systems, which are recognized as a critical contributor to nosocomial infections. Objectives: This study aimed to determine antibiotic susceptibility profiles and vancomycin-resistance Enterococcus (VRE) isolates in Zahedan, Iran. Methods: A hospital-based cross-sectional study was conducted at Ali Ibne Abi Talib Hospital from March 2019 to February 2022. Clinical samples included urine, blood, abscesses and other body fluids from patients referred to this hospital during the study period. A total of 3000 patients were included in the study, and the Kirby-Bauer method was used to test isolates identified by morphological and biochemical characteristics for antibiotic susceptibility. Data were analyzed using SPSS software version 20. P-values < 0.05 were considered statistically significant. Results: Out of 3000 culture-positive clinical samples comprised of 82 urine, ten blood, one tracheal, two wound, and one pulmonary isolate, were identified as Enterococcus faecalis (69.1%), Enterococcus faecium (7.3%), and Enterococcus spp. (23.6%). Moreover, two-thirds of isolates were multidrug-resistant (MDR). Although 66.7% and 63.9% were sensitive to nitrofurantoin and linezolid, resistance to ciprofloxacin (74.2%) and ampicillin (65.9%) was frequently observed. Nitrofurantoin or linezolid were the only effective antibiotics for UTIs. In addition, 50% of isolates were resistant to vancomycin. Conclusions: Based on the results, a combination of vancomycin/or linezolid and nitrofurantoin for urine infections was effective against Enterococci in this clinical center. Nevertheless, continuous and frequent surveillance for resistance patterns is necessary for the reasonable and evidence-based use of antibiotics.

Application of a liposomal subunit vaccine in chickens for reduction of Campylobacter gut colonisation

Abstract Introduction Campylobacter are the most common cause of food poisoning, which manifests itself in diarrhoea of varying severity. Additionally, because of the increasing number of people with immune deficiencies, more frequent serious complications of Campylobacter infections are being observed. The main source of infection is the consumption of contaminated poultry meat, which is a consequence of the insufficiency of current hygiene and biosecurity to control Campylobacter or eliminate it from the poultry food chain. Material and Methods Two hybrid proteins, presenting selected epitopes of the Campylobacter antigens CjaD and EF-Tu, were developed based on the highly immunogenic proteins CjaA and CjaC. Four groups of chickens were vaccinated with different preparations (a mixture of both hybrid proteins encapsulated in anionic or neutral liposomes) and different doses (a single dose given on the day of hatching or two doses given on days 1 and 14 of life). The number of Campylobacter was assessed in the intestinal contents of vaccinated birds. Results No statistically significant differences in colonisation levels were observed between chickens immunised with neutral liposomes containing hybrid proteins and their non-immunised counterparts, regardless of dosage regimen. Conclusion Although immunisation of chickens did not produce the expected results, the approach used has great potential, which is worth further investigation and development.

A comprehensive analysis of the defense responses of Odontotermes formosanus (Shiraki) provides insights into the changes during Serratia marcescens infection

BackgroundOdontotermes formosanus (Shiraki) is a highly damaging agroforestry pest. Serratia marcescens is a broad-spectrum insecticidal pathogen and is highly lethal to O. formosanus. However, little is known about the mechanism between them. To improve the biological control of pests, a more in-depth analysis of the interactions between the pests and the pathogens is essential.ResultsWe used RNA-seq, enzyme activity assays and real-time fluorescent quantitative PCR (qPCR) to explore the defense responses of O. formosanus against SM1. RNA-seq results showed that 1,160, 2,531 and 4,536 genes were differentially expressed at 3, 6 and 12 h after SM1 infection, and Kyoto Encyclopedia of Genes and Genomes (KEGG) results indicated that immune response and energy metabolism were involved in the defense of O. formosanus against SM1. Reactive oxygen species (ROS) levels and ROS synthesis genes were significantly elevated, and the antioxidant system were induced in O. formosanus after SM1 infection. In addition, the cellular immune genes were affected, and the Toll, immune deficiency (Imd), Janus kinase/signal transducer and activator of transcription (JAK/STAT), c-Jun N-terminal Kinase (JNK) and melanization pathways were activated. In vitro, Oftermicin, an antimicrobial peptide, had a significantly inhibitory effect on SM1. Furthermore, the expression levels and enzyme activities of phosphofructokinase (PFK), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH) and isocitrate dehydrogenase (IDH) in glycolysis and tricarboxylic acid (TCA) cycles were increased.ConclusionsOur results clearly demonstrated that O. formosanus defended against SM1 by activating the antioxidant system, innate immunity and energy metabolism. This study would provide useful information for the development of biological controls of O. formosanus.

Investigation on improving immunologic reconstitution insufficiency using DiwuYanggan capsules in AIDS patients

BackgroundThis study aimed to explore the mechanism of action of DiWuYangGan (DWYG) capsule in improving Immunological non-responder (INR) by analyzing the active ingredients of DWYG.MethodsThe study employed a randomized, controlled, double-blind, single-simulation method. Patients were randomly divided into control and trial groups and treated with the primal highly effective antiretroviral therapy. To demonstrate the effect of DWYG on INR, patients in the control group were administered simulated DWYG, whereas patients in the trial group were administered DWYG capsules (ChiCTR1900024673). The chemical composition of DWYG was analyzed using ultra-performance liquid chromatography-high-resolution mass spectrometry. Potential targets of DWYG in the treatment of INR were identified and predicted using network pharmacology and molecular docking. The molecular mechanisms underlying the effects of DWYG were validated using a peripheral blood monocyte model.ResultsThe CD4:CD8 ratio in the trial group was significantly higher than that in the control group (p < 0.01). A total of 210 DWYG compounds were identified and network pharmacology revealed 182 potential therapeutic targets for DWYG and INR. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the toll-like receptor signaling pathway is one of the key pathways. This study demonstrated that DWYG reduced the expression level of TLR4 and the levels of IL-2, IL-10, and TNF-α, which are important cytokines involved in the immune response.ConclusionThe efficacy of DWYG in the treatment of INR confirmed the potential practical components of DWYG. Moreover, the results of network pharmacology and experimental validation showed that DWYG could restore the immune function of acquired immune deficiency syndrome patients by inhibiting the expression of TLR4 and related signaling pathways and the overactivation of immune function.Clinical Trial Registration:https://www.chictr.org.cn/index.html, identifier ChiCTR1900024673.

Clinical profile of herpes zoster-related hospitalizations and complications: A French population-based database study

To estimate the incidence of hospitalization with a diagnosis of herpes zoster (HZ) and post-herpetic neuralgia (PHN) in France between 2013 and 2020, overall and stratified by age-group and immune status. Retrospective observational, database study, using the French hospital discharge database, which includes private and public data for all day-care and inpatient stays. Adults aged ≥18 years, hospitalized between January 1, 2013, and December 31, 2020, with a diagnosis of HZ or PHN were included. Overall, 62 077 adults had a first hospitalization with a diagnosis of HZ or PHN during the observation period. HZ and/or PHN incidence ranged between 14.6 and 16.3 hospitalizations/100 000 persons and was highest in people aged ≥80 years (97.6 hospitalizations/100 000 persons). The immunocompromised (IC) population accounted for 22% of the overall study population. IC patients had longer lengths of stay for HZ per episode compared with non-IC patients (15.5 ± 19.4 days vs 12.2 ± 13.5 days) and higher in-patient mortality (8% vs 4%). Average annual hospitalization costs per patient were higher in the IC vs non-IC population (€8018 vs €5603). Older age increases hospitalization rates up to 6-fold and IC status increases in-patient mortality up to two-fold.

Hematologic cancers and infections: how to detect infections in advance and determine the type?

Infection is one of the leading causes of death in patients with hematologic cancers. Hematologic cancer patients with compromised immune systems are already susceptible to infections, which come on even more rapidly and are difficult to control after they develop neutrophil deficiencies from high-dose chemotherapy. After patients have developed an infection, the determination of the type of infection becomes a priority for clinicians. In this review, we summarize the biomarkers currently used for the prediction of infections in patients with hematologic cancers; procalcitonin, CD64, cytokines, and CD14 et al. can be used to determine bacterial infections, and (1-3)-β-D-glucan and galactomannan et al. can be used as a determination of fungal infections. We have also focused on the use of metagenomic next-generation sequencing in infections in patients with hematologic cancers, which has excellent clinical value in infection prediction and can detect microorganisms that cannot be detected by conventional testing methods such as blood cultures. Of course, we also focused on infection biomarkers that are not yet used in blood cancer patients but could be used as a future research direction, e.g., human neutrophil lipocalin, serum amyloid A, and heparin-binding protein et al. Finally, clinicians need to combine multiple infection biomarkers, the patient’s clinical condition, local susceptibility to the type of infection, and many other factors to make a determination of the type of infection.

Immune defense adaptation of Strauchbufo raddei population in heavy metal polluted area: Insights from developmental and environmental perspectives

The adjustment of immune defense mechanisms is a crucial aspect of biological adaptation to stressful environments. Amphibians, with their unique metamorphic process, experience distinct life stages and exhibit diverse immune defense components. While previous studies have focused on specific immune changes during particular life stages under stress, this research addresses a critical gap by exploring the adaptive immune defense strategies of Strauchbufo raddei in heavy metal-polluted environments. We conducted laboratory experiments, exposing offspring from both polluted and unpolluted areas to control and heavy metal treatments, while continuously monitoring changes in immune components during key metamorphic stages. Notably, we examined the role of the skin microbiome, a crucial but often overlooked barrier against pathogens. The results indicated that individuals from polluted areas exhibited some tolerance to heavy metal exposure, though overall immune function remained diminished. During metamorphosis, when immune defenses are most vulnerable, the skin microbiome rapidly enriched beneficial bacteria, preventing pathogenic colonization and playing a pivotal role in maintaining immune defense in contaminated environments. Moreover, our research highlights energy allocation strategies involving corticosterone and body fat content, enabling populations to maintain development despite immune compromise. The immune adaptations observed may be fixed through genetic assimilation, suggesting a rapid evolutionary response to environmental stress. However, this reduces phenotypic plasticity, making populations more vulnerable to future environmental changes. This study provides key insights into the survival strategies of amphibian populations in heavy metal-contaminated areas, laying the foundation for future research on molecular and evolutionary adaptations.

Lumbosacral rotation flap: a simple method for covering sacral pressure injuries.

Pressure injuries (PIs) are among the most common skin and soft tissue wounds occurring in patients who are bedbound and/or immobile. PI management hinges on their prevention; however, reoccurrence poses a challenge to their management and requires a multidisciplinary approach. Here, the authors describe a lumbosacral rotation flap (LSRF) for the coverage of sacral PIs. A single-centre, retrospective analysis of prospectively collected data was carried out. All patients undergoing LSRF for sacral PIs were included. Patients with active systemic sepsis, immune compromise, hepatic or renal dysfunction were excluded. All patients underwent preoperative optimisation and wound cultures to direct antibiotic therapy after surgery. A total of nine patients underwent the procedure (seven male and two female). Mean age was 47.6 years with a mean ulcer size of 92.9 cm2. Bone biopsy indicated the presence of osteomyelitis in three patients. Of the LSRFs, two flaps showed minimal local complications in the form of marginal flap necrosis which was managed conservatively. All flaps healed well with no cases of flap loss or the need for secondary procedures. The results of this analysis showed that LSRF can be considered a first line of treatment of sacral PIs. They can be used to cover large defects. Due to their large base and flap size, readvancement in cases of recurrence is also possible.

Wealth-related disparities of comprehensive knowledge of HIV among reproductive-aged women in Ethiopia: a decomposition analysis

IntroductionHuman Immunodeficiency Virus and Acquired Immune Deficiency Syndrome (HIV/AIDS) remains a major global public health concern, especially in low-income countries like Ethiopia. Insufficient awareness about HIV/AIDS makes women vulnerable to infection. Notably, there is a disparity in the comprehensive HIV knowledge among reproductive-aged women in poorer and wealthier households. However, the contributing factors for wealth-related disparities in comprehensive knowledge of HIV among reproductive-aged women in Ethiopia have not been explored.MethodsWe used the women's record (IR) of the 2016 Ethiopian demographic health survey. Erreygers normalized concentration index and curve were used to analyze the percentage contribution of factors in the comprehensive knowledge of HIV difference across wealth index. The concentration index was decomposed into contributing factors for poor comprehensive knowledge among poorer households.ResultsA total of 14,599 reproductive-aged women were included in the analysis. The comprehensive knowledge of HIV was 14.75% and 29.33% in the poorest and wealthiest households, respectively. The weighted Erreygers normalized concentration index (ECI) was 0.11 with Standard error = 0.015 (P value < 0.05). Age (− 0.17%), residence (1.4%), education (26.2%), occupation (1.38%), region (0.61%), wealth index (30.8%), media exposure (13.4%), and internet access (0.67%) significantly contributed to the wealth-related inequalities.ConclusionThere was a pro-rich distribution of comprehensive knowledge of HIV among reproductive-age women in Ethiopia. Wealth, education, and media exposure were the major contributing factors to the wealth-related inequalities. Policymakers should prioritize media exposure and education, and work to improve the comprehensive knowledge of women in poorer households.

Primary cutaneous infections with non-tuberculous mycobacteria: a report of 6 cases

BackgroundThe incidence of non-tuberculous mycobacterium infection has shown a gradual increasing trend in recent years, among which cutaneous manifestations as an important aspect. This study aimed to describe the clinical features and microbiological findings in 6 cases of primary cutaneous nontuberculous mycobacterium infection.MethodsIn this retrospective study from June 2021 to June 2022, the clinical data and microbiological results of six cases diagnosed with primary cutaneous non-tuberculous mycobacterium infection in department of dermatology, Hangzhou Third People’s Hospital were analyzed.ResultsAll six cases were primary cutaneous non-tuberculous mycobacterium infections, four of which had a history of trauma or exposure, and two had an underlying disease that could lead to compromised immunity. All patients presented with erythema nodular skin lesions, four on the upper or lower extremities, one on the face, and one on the right hip. The histopathological findings of five patients who underwent biopsy were granulomatous inflammatory changes with mixed infiltration. Laboratory cultures using tissue or tissue fluid were all successful, including four Mycobacterium marinum, one Mycobacterium abscessus, and one Mycobacterium avium. Metagenomics next-generation sequencing detected results consistent with culture colonies in only two cases. With the exception of case 4, all patients responded well to oral medication, with a course of treatment ranging from 4 months to 1 year, and the prognosis was good.ConclusionsThe clinical features of primary cutaneous non-tuberculous mycobacterium infection are often lacking in specificity, and the identification of related strains is difficult for a variety of reasons. Although the results of metagenomics next-generation sequencing are useful for pathogen spectrum identification, its diagnostic value should be carefully reevaluated under certain circumstances. Patients with suspected triggers who do not respond well to conventional treatments should be suspected as atypical infection and potential immunosuppression. If diagnosed and treated promptly, the prognosis of primary cutaneous non-tuberculous mycobacterium infection is generally good.

Evaluation of the immunomodulatory effects of a novel synbiotic made of combined use of probiotic-prebiotic-Chinese traditional herbs

BackgroundRecent studies have discussed the preferred activity of synbiotics, which are a combination of probiotics and prebiotics. This study formulates a novel synbiotic that includes Chinese traditional herbs and evaluates its immunomodulatory function. PurposeThis study aims to systematically investigate the effects of synbiotics on immune function using a cyclophosphamide-induced immunosuppressed mouse model. Study DesignA literature-based approach was used to selectively identify medicinal herbs with immunomodulatory properties. Commercially available probiotics were used to investigate the immunomodulatory functions and potential mechanisms associated with the combination of Chinese medicinal herbs and prebiotics as carbon substrates. MethodsThe immunomodulatory effect of the synbiotic will be assessed by measuring indicators such as body weight, organ index, immunoglobulins, cytokines, splenic lymphocyte proliferation status, NK cell cytotoxicity and gut microbiota. ResultsOur results demonstrated that the synbiotic significantly restored the decreased thymus index and the increased spleen index induced by immune deficiency in mice. Among them, the formula of the synbiotics significantly improves the thymus organ index of immune organs from 0.068 to 0.126, which is also significantly superior compared to other single components. Additionally, it significantly enhanced the proliferative capacity of splenic lymphocytes and the cytotoxic activity of natural killer (NK) cells in immune-deficient mice. Furthermore, the synbiotics enhanced the richness and diversity of the gut microbiota, rectifying the dysbiosis in gut microbial composition caused by immune deficiency. It decreased the relative abundance of Firmicutes from 67.41% to 44.06%, while increasing the relative abundance of Bacteroidota from 30.42% to 53.77%. It restored the disrupted gut microbial structure induced by cyclophosphamide damage, thereby ameliorating the disrupted intestinal microbial community associated with immune deficiency. ConclusionThe study demonstrated that the synbiotic was capable of modulating immune function, as evidenced by an increase in organ index, cellular immunity, and the ability to modulate intestinal flora disorders. Furthermore, the synbiotic demonstrated superior performance compared to other single components.

Rare Variants of DNA Ligase 1 Show Distinct Mechanisms of Deficiency

Human DNA ligase 1 (LIG1) performs the final step in DNA repair and recombination pathways by sealing DNA breaks, and it functions as the main replicative ligase. Hypomorphic LIG1 variants R771W and R641L cause immune deficiencies in LIG1 Syndrome patients. In vitro these LIG1 variants have decreased catalytic efficiency and increased abortive ligation and it is not known if either biochemical defect is sufficient on its own to cause immune deficiency. We investigated the enzymatic activity of several new candidate LIG1 Syndrome variants chosen based on their structural proximity to known clinical variants, low minor allele frequency (MAF), high level of conservation, and concurrence in patients with similar symptoms as LIG1 Syndrome patients. The R305Q substitution is in the DNA binding domain, R768W is in the OB-fold domain, and R641S is in the nucleotidyltransferase domain. Biochemical characterization confirmed deficiencies in ligase activity for all three variants, but also revealed marked differences in comparison to the known LIG1 Syndrome variants. Both the R305Q and R768W substitutions increase the KM for DNA and decrease the catalytic efficiency, however, neither exhibit elevated levels of abortive ligation. In contrast, the R641S variant exhibits a greater impairment of activity as well as a more pronounced level of abortive ligation compared to the known LIG1 Syndrome variant, R641L. This work expands the number of LIG1 alleles that are likely candidates for LIG1 Syndrome, and it raises the question of whether distinct enzymatic deficiencies in LIG1 cause unique clinical impacts in patients harboring these alleles.

The role and mechanism of BmsPLA2-1-1 in the IMD pathway in silkworm, Bomybx mori

Lepidoptera are a major source of pests in agriculture and forestry, investigating the immune mechanisms of their model species, Bombyx mori, can provide valuable insights into improving pest management. Although the phospholipase A2 (PLA2) and immune deficiency (IMD) pathway have been extensively investigated, their relationship remains unclear. Here, we found that bacterial infection of silkworm larvae significantly upregulated BmsPLA2-1-1 expression and knockdown of BmRelish in the IMD pathway suppressed this response. Likewise, reducing BmsPLA2-1-1 expression significantly downregulated IMD pathway-related genes, including BmRelish, BmImd, and BmPGRP. In contrast, overexpression of BmsPLA2-1-1 significantly upregulated BmRelish and BmImd expression, suggesting a functional crosstalk between BmsPLA2-1-1 and the IMD pathway in silkworms. Additionally, BmPLA2-1-1 interacted with BmHsp60, BmCNBP, BmCfp1, and BmPFD3. Reducing BmRelish resulted in decreased expression of BmHsp60A, BmCfp1, and BmPFD3, but not BmCNBP, in infected larvae. Overexpression BmHsp60A, BmCfp1, or BmPFD3 led to a significant upregulation of BmRelish and BmImd expression. These suggest that BmHsp60A, BmCfp1, and BmPFD3 are involved in functional crosstalk between BmsPLA2-1-1 and the IMD pathway in silkworms. These findings demonstrate the functional crosstalk and mechanism between BmsPLA2-1-1 and the IMD pathway, revealing a new mechanism in the insect immune network.