We report a case of epidermolysis bullosa acquisita (EBA) in a 47-year-old man who suffered for more than 10 years. To evaluate the longitudinal immunological changes, we measured serum levels of anti-basement membrane zone (BMZ) IgG antibodies by indirect immunofluorescence and anti-type VII collagen antibodies by enzyme-linked immunosorbent assay throughout the clinical course. In addition, serum concentrations of B-cell activating factor (BAFF), interleukin (IL)-9, and IL-10 were measured. Titers of anti-BMZ antibodies and anti-type VII collagen antibodies fluctuated during the follow-up period and corresponded broadly with clinical disease activity. Serum BAFF levels increased before the marked elevation of anti-type VII collagen antibody titers, although they did not closely parallel disease activity. Serum IL-9 showed a transient peak around the time when the anti-type VII collagen antibody titer reached its maximum. Serum IL-10 increased after the peak of the anti-type VII collagen antibody titer. These temporal changes in BAFF, IL-9, and IL-10 observed may provide useful information for understanding the immunological phases of EBA.

Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL) is a rare, aggressive variant of diffuse LBCL with an immunoblastic/plasmablastic morphology, a plasmacytic immunophenotype with loss of conventional B-cell antigens, and granular cytoplasmic ALK expression. Involvement of the gastrointestinal tract has been documented only in the stomach, duodenum, and ileum. To the best of our knowledge, we report the first case presenting at the esophagogastric junction. A 71-year-old immunocompetent man with Parkinson's disease was referred for progressive anemia that had been detected incidentally, and was found to have a submucosal tumor-like lesion with surface ulceration at the esophagogastric junction, despite a normal serum lactate dehydrogenase level. An endoscopic biopsy revealed diffuse sheets of large immunoblastic and plasmablastic cells. The cells were positive for CD138, multiple myeloma oncogene 1 (MUM1), epithelial membrane antigen (EMA), c-Myc, and CD4; exhibited lambda light-chain restriction; displayed granular cytoplasmic ALK positivity; and weakly expressed CD79a and paired box 5 (PAX5) in Golgi pattern and diffuse patterns, respectively. They were negative for CD30, CD3, CD5, CD8, Epstein-Barr virus-encoded small RNA, human herpesvirus-8, and pan-cytokeratin. Break-apart fluorescence in situ hybridization confirmed ALK rearrangement. Positron emission tomography demonstrated Ann Arbor stage IV disease, with nodal region involvement on both sides of the diaphragm in addition to the gastric cardia. This case illustrates a multilayered clinical, morphological, and immunophenotypic diagnostic pitfall, which was nonetheless resolved through endoscopic biopsy alone. The diagnostic value of this report lies in the lessons for avoiding misdiagnosis rather than in the rarity of the anatomical site.

Bipolar disorder (BD) is a heterogeneous mood disorder that lacks robust biomarkers for biological stratification. We used high-throughput plasma proteomics to characterize case-control differences, identify proteomic subgroups within BD, and examine their associations with blood-based markers and clinical features. Plasma samples from the French I-GIVE (Immuno-Genetics, Inflammation, retroVirus, Environment) cohort, including 248 participants with BD and 76 healthy controls, were assessed using the Olink Reveal panel (1,034 proteins). Age-, sex-, and BMI-adjusted case-control analyses identified 527 differentially expressed proteins in the imputed analysis and 136 in the complete-case analysis, with high agreement in effect estimates and involvement of immune, metabolic, oxidative stress, and endothelial-related processes. Despite the large number of differentially expressed proteins, pathway enrichment was limited to B-cell receptor and chronic myeloid leukemia-related signaling in BD. Unsupervised clustering within BD identified two proteomic subgroups, with enrichment between clusters in longevity-regulating pathways, cellular senescence, FLT3 signaling, and transcription-related pathways. Among four measured inflammatory/endothelial markers, serum amyloid A was the only marker showing a significant difference between groups (FDR < 0.05). Clinical characteristics were similar across clusters, although childhood physical abuse and a greater somatic comorbidity burden were associated with the subgroup showing higher protein abundance. Our findings support biological heterogeneity within BD and suggest that proteomic subgrouping may capture variation not evident in pooled case-control analyses.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, and its onset and progression are closely related to age-related remodeling of the immune system. Immunosenescence refers to age-related changes in the overall structure and function of the immune system; inflammaging is a persistent, low-grade, systemic inflammatory state; cellular senescence refers to a relatively stable cell cycle arrest and functional remodeling of cells under continuous stress. These three are interrelated but correspond to the immune system, systemic inflammatory environment, and cellular state, respectively; therefore, they should not be used interchangeably. In RA, especially elderly-onset RA (EORA), immune age-related changes may occur earlier or be more severe. Human studies on RA mainly support that immune cell lineage remodeling, senescence-associated cell phenotypes, and changes in inflammatory mediators are associated with disease activity, structural damage, and some extra-articular comorbidities. Immunosenescence may compromise T-cell, B-cell, and innate immune functions; concurrently, local cellular senescence and the senescence-associated secretory phenotype (SASP) may drive synovial and bone marrow microenvironment remodeling, while inflammaging may further amplify systemic inflammation. Impaired immune clearance, accumulation of senescent cells, and SASP release may establish a self-perpetuating cycle and are associated with autoantibody production, bone loss, cartilage damage, and cardiovascular and neuropsychiatric comorbidities. However, causal evidence for SASP-driven RA synovitis and the efficacy of senolytic interventions is still primarily derived from experimental arthritis, osteoarthritis, and other non-RA disease models. This article clarifies the definitions and delineates the applicable boundaries of these three terms, reviews their systemic phenotypes, cell lineage characteristics, and molecular basis in RA, especially EORA, analyzes the links between immune age and disease activity, autoantibodies, synovial microenvironment, bone and cartilage damage, and extra-articular manifestations, and evaluates the potential benefits, risks, and evidence limitations of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, and emerging senescence-targeting strategies. By constructing an integrated framework covering immune system remodeling, local cellular senescence, inflammatory amplification, and clinical outcomes, this article aims to provide a theoretical basis for further research on EORA risk stratification and immunosenescence-related interventions, rather than directly translating unverified mechanisms into clinical conclusions.

Primary amoebic meningoencephalitis (PAM) is caused by Naegleria fowleri, a free-living amoeba. It is a fatal infection with more than 95% mortality rate. Even though several combinations of antimicrobial agents were used to treat the condition, the overall survival remains poor and no effective vaccine is currently available. In this study, an immunoinformatic approach was utilized for designing a multi-epitope vaccine against N. fowleri. The sequences of antigenic proteins were retrieved for epitope prediction. The computational prediction identified 400 CTL, 590 HTL, and 65 B-cell high-binding epitopes. After evaluating their antigenicity, allergenicity and toxicity, 5 CTL, 5 HTL and 3 B-cell epitopes were selected and assembled into a multi-epitope vaccine construct using linkers and a human β-defensin-3 adjuvant. The 3D structure of the vaccine was predicted using AlphaFold and refined with GalaxyRefine. Ramachandran plot analysis indicated that 96.5% of the residues of the refined vaccine are present in the most favored regions, indicating good stereochemical quality. The molecular docking analysis was performed using HADDOCK to evaluate the interaction between the vaccine and the Toll-like Receptors (TLRs), which predicted favorable binding affinities of -15.6 kcal/mol, -14.2 kcal/mol, and - 13.1 kcal/mol for TLR1 & 2, TLR3, and TLR4, respectively. The codon was optimized using JCat and cloned into the pET-28a(+) plasmid. The in silico immune simulation analysis predicted potential humoral and cellular immune responses to the vaccine construct. Overall, the proposed multi-epitope vaccine represents a promising computational candidate, however, further experimental validations have to be performed to confirm its efficacy against the pathogen.

Infectious bronchitis virus (IBV) causes severe economic losses to the poultry industry. The IBV S1-CTD mediates receptor binding and serves as a key target for antibody recognition. In this study, the S1-CTD protein of the QX-type IBV QXL87 strain was expressed in HEK293F cells. Four monoclonal antibodies (10H5, 11D11, 12H7, and 13H1) were generated via hybridoma technology and characterized by indirect ELISA, Western blotting, and immunofluorescence assay; variable-region sequencing showed that the four mAbs are clonally related and recognize the same antigenic region. Using overlapping peptide scanning, a novel linear B-cell epitope (283AQPNSGGVNTFHLYQ297) was identified within the S1-CTD. Alanine scanning mutagenesis revealed that residues 286N, 293F, 295L and 296Y are critical for antibody recognition. Additionally, residue 292T was identified as an ancillary contact site that contributes to the binding of a subset of the mAbs. Computational structural modeling suggested that this epitope is located within a predicted surface-exposed flexible loop of the S1-CTD, a conformation that may be favorable for antibody binding. Sequence analysis revealed that, among the representative genotypes circulating in China examined in this study, the critical residues of this epitope are conserved only in GI-19 and GI-13, with variations observed in the other genotypes; the critical residues were also fully conserved in the North American GI-9 (Arkansas) strains included for comparison. This study provides the first fine mapping of a linear B-cell epitope within the S1-CTD of QX-type IBV, and identifies a candidate target that may inform the future development of genotype-specific serological detection tools for IBV.

Loss of immune tolerance to commensal microbial antigens is a central driver of inflammatory bowel disease. While regulatory T cells are well recognized in maintaining intestinal homeostasis, the contribution of B cells-particularly IgA-secreting cells-remains incompletely defined. In the T cell transfer colitis model, cotransfer of splenic B cells attenuates disease, an effect largely attributed to IL-10-producing regulatory B cells (Bregs). However, alternative B cell-dependent mechanisms have not been fully explored. Here, we investigated whether splenic B cells regulate T cell transfer colitis through IgA-dependent mechanisms independent of Breg-associated cytokines. We show that splenic B cells from wild-type C57BL/6 (B6) mice reconstitute bone marrow and peripheral B cell compartments in RAG1⁻/⁻ recipients, undergo class switching, migrate to the colonic lamina propria as sIgA⁺ B lineage cells, and partially restore luminal secretory IgA. B cell cotransfer significantly attenuated clinical and histological colitis without increased expression of canonical Breg-associated cytokines, including interleukin-10, transforming growth factor β, and interleukin-35 subunits. In contrast, splenic B cells from IgA-deficient mice failed to attenuate colitis despite comparable peripheral B cell reconstitution. Restoration of secretory IgA was associated with increased bacterial IgA coating, reduced fecal bacterial burden, and remodeling of the colonic microbiota, including enrichment of beneficial commensal taxa. Importantly, because IgA-deficient B cells failed to attenuate colitis despite comparable peripheral B cell reconstitution, these findings support an important role for IgA in mediating the protective effect of B cell transfer. Collectively, these findings identify IgA-mediated modulation of the microbiota as an alternate mechanism by which B cells attenuate T cell transfer colitis, highlighting a Breg-independent regulatory pathway with potential relevance to inflammatory bowel disease pathogenesis.

Despite effective antivirals, Hepatitis C remains a global health burden, reflecting the difficulty of eliciting broadly neutralizing antibodies (bnAbs). For the Hepatitis C virus, bnAb responses are biased toward VH1-69-encoded Abs targeting a conserved epitope on the E2 glycoprotein, suggesting that effective immunogens must engage the corresponding germline (GL) B cell receptors. However, the structural basis of GL recognition remains unclear. Here, we show that GL-reverted VH1-69 bnAbs recognize the E2 core domain in a manner closely resembling mature Abs binding. High-resolution structures reveal a conserved mode of engagement, indicating that key epitope features are accessible prior to affinity maturation. Guided by these insights, we engineered E2 variants to enhance GL Ab interactions and stability. Although these designs increased affinity, they did not improve engagement of naïve B cells, highlighting a key constraint in GL-targeting strategies. Together, our findings define principles governing GL recognition and inform the rational design of an HCV vaccine.

Primary cardiac tumors are rare, and cardiac lymphomas are particularly uncommon. Their presentation can mimic benign tumors, but perioperative management is highly challenging due to risks of tumor-related obstruction or invasion of surrounding cardiac structures. We present a 76-year-old woman with rapidly progressing dyspnea, found to have large biatrial masses, significant pericardial and pleural effusions, and evidence of tamponade. The patient underwent successful surgical resection of bilateral atrial tumors after careful anesthetic preparation and intraoperative monitoring. Histology revealed diffuse large B-cell lymphoma, and systemic chemotherapy was commenced. This case highlights the critical importance of multidisciplinary collaboration, preoperative hemodynamic stabilization, careful anesthetic planning, and prompt histological diagnosis in managing primary cardiac lymphoma presenting with tamponade physiology.

Rheumatoid arthritis pathogenesis is perpetuated by a self-sustaining oxidative stress-immunodysregulation circuit. To address the limitations of conventional antioxidants, including unclear catalytic structures and single catalytic activity, we engineered copper single-atom carbon dots via topological transformation of sodium copper chlorophyllin. Encapsulated within a pH-responsive injectable hydrogel, this system achieves targeted delivery to inflamed joints, where it simultaneously scavenges superoxide anions and hydrogen peroxide, breaking the reactive oxygen species-inflammation cycle. Treatment reprograms macrophage polarization, suppresses pathogenic B-cell infiltration, and mitigates cartilage erosion. By integrating nature-inspired atomic catalysis with intelligent biomaterial engineering, this approach establishes a paradigm for resetting oxidative-immune microenvironments in autoimmune diseases.

Multiple myeloma (MM) is frequently associated with renal impairment, most commonly due to cast nephropathy. We report a case of severe and persistent postoperative acute kidney injury (AKI) in an 84-year-old man with smoldering MM who underwent posterior lumbar fixation for a lumbar burst fracture. Twelve hours after surgery, he developed profound hypotension and severe anemia due to surgical-site bleeding, followed by progressive renal dysfunction despite prompt transfusion and fluid resuscitation. Urinalysis revealed heavy proteinuria, and kidney biopsy demonstrated marked accumulation of eosinophilic casts within the tubules, consistent with cast nephropathy. In addition, marked renal interstitial infiltration by λ light-chain-restricted monoclonal plasma cells and focal peritubular capillary (PTC) occlusion were observed. Congo red staining was negative, and no significant glomerular immune deposits were detected. Renal function partially improved with supportive care but did not return to the preoperative baseline. This case suggests that postoperative AKI in MM may be multifactorial, with perioperative circulatory failure precipitating clinically overt cast nephropathy, while coexisting interstitial myeloma cell infiltration and focal PTC occlusion may increase susceptibility to ischemic injury and contribute to the severity and persistence of renal dysfunction. In patients with MM, latent myeloma-related kidney injury should be considered a potential contributor to perioperative AKI even when serum creatinine is preserved, particularly in those with marked proteinuria or elevated free light chain levels.

Trogocytosis is a unique intercellular process that can occur when two cells become in contact to each other and one cell "nibbles" portions of another cell's membrane and surface molecules. This phenomenon is widely observed among immune cells such as B cells, T cells, NK cells, and antigen-presenting cells (APCs). Through trogocytosis, molecules including major histocompatibility complexes (MHC), costimulatory receptors, and antigens are transferred, influencing cellular communication and immune regulation. While trogocytosis supports processes like antigen presentation, immune activation, and neural remodeling, it also contributes to pathological conditions, including tumor immune evasion, therapeutic resistance, and pathogen dissemination. This duality raises critical questions about its overall impact: is trogocytosis a friend or foe to the immune system? By comparing trogocytosis to phagocytosis, exploring molecular mechanisms, and examining its roles in health and disease, this review synthesizes current findings and highlights areas for future investigation. Understanding the precise mechanisms governing trogocytosis could pave the way for innovative therapies targeting infections, cancers, and autoimmune disorders.