BMC Immunology最新文献

Background: The clinical presentation of COVID-19 varies significantly by viral variant; the Delta variant often causes severe lung inflammation, whereas Omicron tends to result in less severe respiratory disease but may more readily affect other organs. The autoimmune mechanisms behind these variant-specific complications, particularly the potential role of anti-neutrophil cytoplasmic (ANCA) antibodies, are still not well defined. This study investigated myeloperoxidase (MPO), proteinase 3 (PR3), and glomerular basement membrane (GBM) antibodies in patients infected with the Delta and Omicron SARS-CoV-2 variants to evaluate their associations with specific clinical complications, such as renal or respiratory involvement.

Methods: Samples were collected during Delta and Omicron outbreaks from hospitalized COVID-19 patients (40 Delta, 40 Omicron) and 40 healthy controls. Serum autoantibodies (MPO, PR3, GBM) were measured via ELISA, and laboratory/clinical data were collected.

Results: All autoantibody levels remained within normal limits. Despite statistical significance (P < 0.05), effect sizes were small (η²=0.085-0.180). Anti-MPO was highest in the Delta group (1.08 U/mL) vs. Control (0.71 U/mL) and Omicron (0.77 U/mL). Anti-PR3 was lowest in the Delta group (0.83 U/mL) vs. Control (1.52 U/mL). Anti-GBM was lowest in the Omicron group (1.48 U/mL) vs. Control (3.48 U/mL) and Delta (3.10 U/mL). Clinically, the Delta group exhibited significantly lower oxygen saturation (92.28% ± 8.69) than the Omicron group (96.15% ± 2.77; P = 0.009). Markers of inflammation and tissue damage-including C-reactive protein (CRP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and coagulation parameters-were markedly elevated in the Delta group compared to the Omicron group (P < 0.001). Conversely, creatinine was significantly higher in the Omicron group (P < 0.001).

Conclusion: While autoantibody levels remained normal, clinical profiles diverged significantly between variants. The Delta variant was associated with heightened systemic inflammation, whereas Omicron was associated with greater organ involvement, suggesting the possibility of distinct pathogenic mechanisms.

Background: Severe combined immunodeficiency (SCID) is a congenital immunodeficiency characterized by significant numerical or functional defects in T lymphocytes and is often accompanied by B lymphocyte dysfunction. It presents early in life with severe, recurrent opportunistic infections. Early diagnosis and hematopoietic stem cell transplantation (HSCT) are vital for patient survival. Cernunnos/XLF deficiency is an autosomal recessive form of SCID caused by mutations in the NHEJ1 gene, which plays a critical role in repairing DNA double-strand breaks. First described in 2006, this condition remains exceedingly rare, with only about 55 cases reported to date. This study aimed to describe a novel infant with Cernunnos/XLF deficiency and to review previously reported patients carrying the same variant, thereby expanding the clinical spectrum of this rare disease.

Methods: With written informed consent, we retrospectively evaluated a pediatric patient with Cernunnos/XLF deficiency followed at our clinic. Demographic, clinical, laboratory, and radiological findings were reviewed. The diagnosis was based on clinical and immunological features and confirmed via clinical exome sequencing. A literature review was conducted to compare the genotype-phenotype correlations of previously reported patients carrying the same NHEJ1 variant.

Results: We report an infant who was hospitalized at 6.5 months of age with a preliminary diagnosis of meningitis and was subsequently diagnosed with Cernunnos/XLF deficiency. The patient exhibited microcephaly, growth retardation, recurrent infections, prolonged SARS-CoV-2 PCR positivity, and localized BCGitis following live Bacillus Calmette-Guérin (BCG) vaccination. Immunological evaluation revealed T- and B-cell lymphopenia and hypogammaglobulinemia. Genetic testing confirmed a homozygous nonsense mutation in NHEJ1. HSCT from a matched sibling donor was performed.

Conclusion: This study describes a rare case of Cernunnos/XLF deficiency diagnosed in early infancy, underscoring the value of early recognition and the critical role of genetic testing and HSCT. It also expands the clinical spectrum of the disease and provides a comparative perspective with previously reported patients carrying the same mutation. In infants presenting with unexplained infections or complications related to live vaccines, inborn errors of immunity should be considered. Our findings emphasize the importance of timely diagnosis and comprehensive, multidisciplinary follow-up, particularly in patients with additional complications.

Objective: Primary Sjögren's syndrome (pSS) is a systemic autoimmune exocrinopathy affecting salivary and lacrimal glands. This study presents an exploratory single-cell transcriptomic analysis of labial salivary glands to generate hypotheses about B-cell-associated gene modules in pSS, and to uncover novel therapeutic targets for B cell modulation in pSS.

Methods: The high-dimensional weighted gene co-expression network analysis (hdWGCNA) was performed on gene expression data obtained from single-cell RNA sequencing (scRNA-seq) of 32,337 cells from labial glands of three pSS patients and three healthy controls. Gene Ontology (GO) enrichment analysis was subsequently conducted to investigate the functional roles of the identified gene modules. Additionally, the scRank method was applied to evaluate the responsiveness of key B cell-related targets across different cell types, providing new insights into the role of B cells in the pathogenesis of pSS.

Results: Through hdWGCNA analysis, we resolved seven co-expression modules in pSS. Module 5, restricted to plasma cells, contains POU2AF1, SLAMF7, SPCS2, CD79A and PDIA6 and is highly enriched for COPI/II-mediated vesicle trafficking and B-cell-receptor signaling, thereby driving autoantibody production and chronic inflammation. Modules 1, 2, 4, 6 and 7 align with extracellular-matrix remodeling, epithelial stress and metabolic reprogramming, underscoring the disease's multifactorial pathobiology. scRank ranked Module 5 as the most drug-responsive cluster and highlighted POU2AF1, SLAMF7 and CD79A as tractable B-cell targets for restoring immune homeostasis in pSS.

Conclusions: Our study identified distinct gene modules associated with pSS, with a particular emphasis on B cells, unveiling novel potential therapeutic targets. The activation of B cells, coupled with immune dysregulation and epithelial dysfunction, appears to play a critical role in pSS pathogenesis, offering valuable insights for developing targeted therapeutic strategies that address both immune activation and tissue repair. These findings nominate B-cell-associated modules-including a plasma cell-enriched module featuring POU2AF1, SLAMF7, and CD79A-as hypotheses for future functional validation.

Background: Type 2 diabetes mellitus (DM) increases both the risk of acquiring latent tuberculosis (TB) infection (LTBI) and progression to active TB. The immunological mechanisms underlying the increased susceptibility remain poorly understood. This study aimed to elucidate the impact of DM on Mtb-specific cytokine and chemokine responses and identify potential biomarkers for LTBI regardless of DM status.

Methods: This cross-sectional study recruited 164 participants with LTBI-DM (n = 51), LTBI-only (n = 63), DM-only (n = 12) and healthy controls (n = 38) at Kiruddu National Referral Hospital. Cytokine and chemokine responses were measured in ESAT-6 and CFP-10 whole blood stimulated supernatants using the Luminex assay. Linear regression with age as a covariate and false discovery rate (p < 0.050) correction were performed on log₂-transformed concentrations. For biomarker analysis, comparisons were performed for LTBI (LTBI-DM + LTBI-only) versus no LTBI (DM-only + healthy controls) groups, and receiver operating characteristic analyses were performed for both univariate and multivariate analyses.

Results: LTBI-DM was associated with decreased Mtb-specific IFN-γ (p_adjusted=0.006), TNF (p_adjusted=0.023), IL-12 (p_adjusted=0.004), IP-10 (p_adjusted=0.004), IL-8 (p_adjusted=0.030) and IL-10 (p_adjusted=0.043) responses compared to LTBI-only. Univariate analysis identified IFN-γ (AUC: 0.80, sensitivity: 81%, specificity: 78%), IL-2 (0.84, 75%, 88%), IL-12 (0.77, 65%, 82%) and IP-10 (0.73, 77%, 62%) as top-performing biomarkers for LTBI identification regardless of DM status. A combined four-marker biosignature yielded an AUC of 0.92 (CI: 0.88-0.97) with 76% sensitivity and 96% specificity.

Conclusion: Diabetes mellitus impairs Th1, inflammatory, and regulatory cytokine and chemokine responses during LTBI. A multivariate biosignature of IFN-γ, IL-2, IL-12 and IP-10 outperforms single-marker assays (e.g., variability in IFN-γ due to immunosuppression in DM) and offers robust identification of LTBI regardless of DM status, highlighting the additive value of combining mediators that capture distinct immunological axes. The improved biosignature specificity may minimise false positives in DM populations, who often exhibit comorbidities that could mimic LTBI-associated inflammation. Our findings support validating combined biomarker approaches to enhance LTBI diagnosis and prognosis in the immunocompromised DM population.

Background and aim: The COVID-19 pandemic has left a lasting imprint on immune function, particularly in the elderly-a population already vulnerable to immunosenescence. While acute and long-COVID immune responses have been widely studied, the long-term apoptotic behavior of peripheral blood mononuclear cells (PBMCs) remains underexplored. This study aims to investigate the legacy of SARS-CoV-2 on PBMC apoptosis in elderly individuals during the post-COVID era, shedding light on potential persistent immune dysregulation.

Materials and methods: In this cross-sectional study, PBMCs were isolated from peripheral blood samples of elderly individuals (> 65 years old) with a documented history of COVID-19 infection at least six months prior. Using multiparametric flow cytometry, we quantified early and late apoptosis markers (Annexin V/PI), mitochondrial membrane potential disruption (ΔΨm), and expression of pro-apoptotic (Bax, Caspase-3) and anti-apoptotic (Bcl-2) proteins. Statistical analyses were performed to assess intergroup differences and correlations with clinical history. This study was conducted in 2025.

Results: Elderly post-COVID individuals exhibited a significantly elevated proportion of apoptotic PBMCs compared to controls (p < 0.01), particularly within the CD4 + and CD8 + T-cell subsets. Mitochondrial depolarization and increased Bax/Bcl-2 ratios indicated a shift toward intrinsic apoptotic pathways. Caspase-3 activation was also heightened in the post-COVID group. Notably, apoptotic burden correlated with time since infection and severity of initial illness.

Discussion: Our findings suggest a prolonged apoptotic signature in the immune cells of elderly individuals following recovery from COVID-19. These alterations may reflect a sustained immune exhaustion or maladaptive remodeling of lymphocyte populations, potentially contributing to impaired immunosurveillance and increased vulnerability to secondary infections or chronic inflammatory conditions.

Conclusion: COVID-19 may cast a long immunological shadow in the elderly, with persistent PBMC apoptosis representing a novel facet of post-viral immune dysregulation. Flow cytometry reveals a unique apoptotic phenotype that could serve as a biomarker for long-term immune health and guide post-pandemic clinical management strategies for aging populations.

The mechanism of epitope mimicry could have implications for the safety of vaccine development. OmpA is one of the most promising antigens of Acinetobacter baumannii. This property convinced us to investigate OmpA's potential to trigger autoimmune responses. To this end, BLAST searches were performed using the OmpA sequence and its overlapping peptides to find identical peptides in the human proteome. These peptides were analyzed for their epitopic and HLA binding properties. The population coverage was then calculated for the peptides. OmpA showed high identity among numerous strains of A. baumannii and had no similar counterparts in the human proteome. Three OmpA peptides (TKNYDSKI, LSLARANS, and GQEAAAPA) shared identity and similarity with human proteins. Amongst, LSLARANS, which was found in Isthmin-1, the one with the highest potential to induce autoimmune responses was identified. LSLARANS was found in a B-cell positive assay of OmpA and acted as an HLA binder (such as HLA-A*03:01). Approximately 18% of the world's population were determined to be more susceptible to probable A. baumannii-post-infection autoimmune disease, which could be rooted in OmpA similarity. Mutation sensitivity analyses indicated that the TKNYDSKI peptide is sensitive to engineering and modification. Given these circumstances, these peptides should be avoided in vaccine design efforts to reduce the risk of autoimmune responses.

Objective: Our research aimed to clarify the roles of M1 and M2 macrophages in leprosy, focusing on their polarization states, phagocytic capacities, and the survival of M. leprae within these macrophage subsets.

Methods: M1-like macrophages were induced by IFN-γ, IL-4 induced M2-like macrophages, and then they were compared with M. leprae-induced macrophages regarding cell-surface antigen expression and cytokine secretion. The phagocytic capabilities of M1-like and M2-like cells were assessed using a laser-scanning confocal microscope. Simultaneously, their bactericidal capacities were evaluated by 16S rRNA/RLEP qPCR to determine the viability of M. leprae.

Results: M1-like macrophages induced by IFN-γ were characterized by CD86 and CD68 expression and an elevated expression of the IRF-5 gene. In contrast, M2-like macrophages induced by IL-4 were distinguished by enhanced expression of CD163 and CD206 markers and the upregulation of the IRF-4 gene. M. leprae-induced macrophages encompass CD86⁺CD68⁺(M1 markers ) and CD163⁺CD206⁺( M2 markers ) subpopulations, potentially displaying characteristics of both M1-like and M2-like phenotypes. M1-like macrophages secreted Th1 cytokines, including IL-1β, IL-6, IL-15, and TNF-α, whereas M2-like macrophages secreted IL-10 and TGF-β. At different stages, macrophages induced by M. leprae released Th1 and Th2 cytokines. The phagocytic ability of M2-like macrophages exceeded that of M1-like macrophages. Nevertheless, M. leprae viability was notably higher in M2-like macrophages, indicating a weaker sterilizing capacity than in M1-like macrophages. Conversely, M1-like macrophages demonstrated potent bactericidal activity, although their phagocytic ability was relatively lower than that of M2-like macrophages.

Conclusion: Our findings suggested the notable significance of macrophage polarization in leprosy. M1 macrophages exhibited a relatively strong bactericidal effect against M. leprae, while M2 macrophages might have been somewhat associated with pathogen persistence.