Immobilized recombinant FcγRIIIa and FcRn receptors as a tool for characterization of human IgG antibodies.

Serum antibody levels against microbial biomarkers of periodontitis, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, are associated especially with the presence of these species in the oral cavity. We investigated the genetic basis of host antibody responses against these species through a genome-wide association study (GWAS) to identify the genetic determinants of this immune reactivity. Serum immunoglobulin A (IgA) and immunoglobulin G (IgG) antibody levels against A. actinomycetemcomitans and P. gingivalis were determined using multiserotype enzyme-linked immunosorbent assay in 3,719 participants from 4 Finnish cohort studies: FinnTwin, Parogene, FINRISK97, and Health-2000. The associations of genetic polymorphisms and imputed human leukocyte antigen (HLA) alleles with antibody levels were investigated. All antibody levels presented significant increasing trends with periodontitis stage and grade. A. actinomycetemcomitans IgG displayed association with single nucleotide polymorphisms (SNPs) in chromosome 6 with lead SNP rs574581129 (near HLA-DRB1, P = 3.6 × 10-8) and P. gingivalis IgG in chromosome 14 with lead SNP rs146761521 (near NUBPL, 5.5 × 10-8). In addition, all antibody levels presented suggestive associations with several loci. Detailed HLA analyses revealed that A. actinomycetemcomitans IgG was associated with DQA1*01:01, DQB1*05:01, and DRB1*01:01 and P. gingivalis IgG with HLA-A*02:01 alleles. Both IgA and IgG antibody levels against microbial biomarker species of periodontitis increase with periodontitis stage and grade, but genetic variation is also a significant predictor. Specific alleles within the HLA region may influence antibody responses to A. actinomycetemcomitans and P. gingivalis, highlighting potential genetic contributions to the immunological mechanisms underlying periodontitis.

N-glycosylation remodeling in aging: Biomarkers and modulators of biological age across organ systems.

Effect of alterations in closeup dietary neutral detergent fiber content on colostrum, transition, and mature milk production and composition in primiparous and multiparous Holstein dairy cattle.

This study hypothesises that a high-starch (HS) diet during the last month of gestation enhances colostrum yield and composition as well as the dam and goat kid metabolism, immune status and performance. Thirty multiparous and pregnant Majorera dairy goats were randomly assigned to a prepartum dietary treatment (CON vs. HS) on wk -4 relative to the expected parturition. Goats were fed either a control (n = 15; 25% DM of starch) or HS (n = 15; 32% DM of starch) diet during the last month of gestation. Blood samples were collected on wk -4, -3, -2 and -1 relative to expected parturition, immediately at parturition (d0) and on d 1, 2, 3, 5, 10, 15, 30 postpartum in dams and goat kids. Colostrum and milk yield were recorded, and gross chemical composition, somatic cell count (SCC), Brix degrees and immunoglobulin G (IgG) concentration were determined on d 0, 1, 2, 3, 5, 10, 15, 30 postpartum. In addition, dam and goat kid blood serum metabolites and plasma IgG concentrations were determined. Data was analysed using linear mixed models in SAS (SAS 9.4) including the prepartum diet, time (T), and the interaction between both as fixed effects. The statistical significance was set as p ≤ 0.05. The high-starch diet did not have any effect either on colostrum nor on milk yield, gross chemical composition, SCC and Brix degrees. However, the excess of starch on the prepartum diet increased colostrum IgG concentration on d 0 (i.e. first milking) in the HS group compared to the control group (i.e. 85.4 and 61.2 mg/mL, respectively). Serum BHB concentration in the HS group increased progressively from wk -3 to parturition (i.e. 0.20 and 0.24 mmol/L, respectively), whereas the control group showed a sharp increase from wk -1 to parturition (i.e. 0.22 and 0.29 mmol/L, respectively). Calcium, total protein, lactate dehydrogenase, urea and albumin concentrations were lower in the HS group compared to the control group during the prepartum period. The high-starch diet prepartum did not influence serum metabolites in the postpartum period except for lactate dehydrogenase, being lower in the first 5 days after parturition in the HS group. In the goat kids, body weight (BW), milk intake and plasma IgG concentrations were not affected by the high-starch diet offered to the dams prepartum except for an increased serum total protein concentration observed on d 1 in the HS group compared to the CON group (i.e. 7.1 vs. 6.5 g/dL, respectively). The present results indicate that a high-starch diet during the last month of gestation does not affect either colostrum yield or composition but increases colostrum IgG concentration, although it did not affect circulating IgG concentrations in goat kids from both groups. Based on the slower fat mobilisation in the HS group, high-starch diets prepartum could promote a smoother transition from late gestation to early lactation in dairy goats. However, other metabolic variables should be considered in future studies.

Oral corticosteroids remain a cornerstone of therapy for generalized myasthenia gravis (gMG) but are associated with substantial long-term toxicity. Efgartigimod, a human immunoglobulinG1 (IgG1) antibody Fc fragment targeting the neonatal Fc receptor (FcRn), has demonstrated efficacy in gMG; however, no prospective trial has evaluated whether regularly scheduled efgartigimod administration can safely reduce oral prednisolone (PSL) dosage. We designed a prospective clinical study to evaluate the steroid-sparing effect of efgartigimod in patients with gMG who remain dependent on ≥ 6mg/day of oral PSL. This is a single-arm, open-label, single-center clinical study. Patients with gMG who are receiving ≥ 6mg/day of oral PSL on a stable dose for at least 4weeks prior to enrollment, with any concomitant oral immunosuppressants also at stable doses for at least 4weeks, and scoring ≥ 5 on the MG Activities of Daily Living (MG-ADL) scale will be enrolled. Efgartigimod will be intravenously administered at 10mg/kg once weekly for 4 consecutive weeks (one cycle), repeated for four cycles with a 28-day interval between cycles. On the fourth administration day of each cycle, oral PSL will be tapered if MG symptoms have not worsened, defined as no ≥ 1-point increase in the MG-ADL score from both baseline and the first administration day of that cycle. The primary endpoint is the change in PSL dosage from baseline at the end of the study. Secondary endpoints include the proportion of patients achieving minimal manifestations (MM) or better status with PSL ≤ 5mg/day (MM-5mg), the time to reach ≤ 5mg/day, the cumulative PSL dose over the study period, the proportion of patients completing the protocol, changes in MG-ADL and other clinical scales, responder rate to efgartigimod, comparison of clinical course between MG subtypes (anti-acetylcholine receptor (AChR) antibody-positive, anti-muscle-specific kinase (MuSK) antibody-positive, and double-seronegative cases) and between patients who are anti-AChR antibody positive, with and without thymoma, changes in indicators of steroid toxicity (HbA1c, lumbar spine bone mineral density, and blood pressure), and the safety profile. The study will also explore biomarkers predictive of efgartigimod response through proteomic and immunologic analyses of serially collected blood samples. Graphical abstract available for this article. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT), CRB3180028; registered on 1 October 2024 (prospectively registered).

Autoimmune hepatitis (AIH) is associated with a high rate of relapse following treatment withdrawal. Identifying noninvasive markers that predict disease recurrence is crucial for long-term management. This study evaluated the prognostic performance of the Fibrosis-4 (FIB-4) Index and the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) in predicting post-treatment relapse in AIH. This retrospective, single-center cohort study included 65 patients with AIH between January 2010 and October 2025 who achieved sustained normalization of transaminase under corticosteroid based therapy and were followed up for at least 12 months. Baseline demographic, laboratory, and noninvasive fibrosis parameters were analyzed. Relapse was defined as alanine aminotransferase or aspartate aminotransferase elevation ≥2 times the upper limit of normal and/or serum immunoglobulin G (IgG) above the upper limit, occurring after complete discontinuation of immunosuppressive therapy. Receiver operating characteristic (ROC) curve analysis and logistic regression were performed. Relapse occurred in 26 patients (40.0%). Patients with relapse had higher baseline serum IgG (P < .001), lower platelet counts (P = .004), and higher APRI and FIB-4 scores (P < .001 for both). ROC analysis identified optimal cutoff values of APRI >1.54 (area under the curve (AUC) = 0.81) and FIB-4 > 3.84 (AUC = 0.80). In multivariate analysis, baseline IgG (odds ratio (OR) = 1.09; 95% CI = 1.00-1.18; P = .049) and FIB-4 > 3.84 (OR = 6.68; 95% CI = 2.02-22.10; P = .002) remained independent predictors. Baseline FIB-4 and serum IgG independently predict relapse following discontinuation of immunosuppressive therapy in AIH and may support individualized follow-up strategies.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) that can lead to end-stage kidney disease and increased mortality. Immunoglobulin G (IgG) from LN patients displays abnormal glycosylation, contributing to podocyte injury. CLEC7A (C-type lectin domain family 7 member A) is a transmembrane lectin receptor that recognizes fucose on IgG. This study investigates the role of lectin-glycan interactions in LN-related podocyte dysfunction. IgG isolated from patients with active lupus nephritis and healthy controls was exposed to differentiated human podocytes. Gene and protein responses were assessed by qPCR, western blotting, immunofluorescence, phalloidin staining, calcium flux, and wound-healing assays. Human kidney biopsies and MRL/lpr mouse kidneys were examined to validate CLEC7A-SYK pathway activation and the glycan-dependent effects of LN-IgG. Human podocytes exposed to the CLEC7A ligand curdlan or LN-IgG, but not healthy control IgG or IgG from SLE patients without nephritis, showed increased CLEC7A expression, impaired motility, cytoskeleton disruption, and reduced nephrin expression. Deglycosylation of LN-IgG blocked CLEC7A binding and preserved podocyte function. Mechanistically, curdlan and LN IgG increased calcium flux and activated spleen tyrosine kinase (SYK). MRL/lpr mice with nephritis exhibited elevated podocyte CLEC7A and SYK expression. Similarly, podocytes in kidney biopsies from patients with active LN exhibit increased expression of SYK and CLEC7A compared to healthy controls. Pharmacological SYK inhibition or CLEC7A silencing prevented podocyte injury. We reveal a novel IgG lectin-glycan-CLEC7A-SYK axis involved in the pathogenesis of LN, which can be targeted therapeutically in patients with LN.

Ribonuclease A (RNase A) is a pancreatic enzyme that rapidly degrades single-stranded RNA and is widely used as a representative enzyme in studies of RNase-mediated RNA degradation. Therefore, effective RNase A inhibitors are needed to regulate RNase activity and protect RNA from enzymatic degradation. Fv-antibodies represent the antigen-binding region of immunoglobulin G (IgG) and are composed of complementarity-determining regions (CDRs) and framework regions (FRs). Previously, CDR3 sequences with RNase A inhibitory activity were screened using RNase A as a probe from an autodisplayed Fv-antibody library constructed by site-directed mutagenesis of the 11-residue CDR3 region and expressed on the outer membrane of Escherichia coli. In this study, these screened CDR3 sequences were synthesized as cyclic peptides by introducing cysteine residues at both the N- and C-termini, enabling intramolecular disulfide bond formation. The metabolic stability of the peptides was enhanced through cyclization, as demonstrated by a significant increase in half-life (t1/2) during liver microsome assays. The RNase A inhibitory activities of Fv-antibodies, linear peptides, and cyclic peptides were analyzed using cyclic cytidine monophosphate (cCMP) hydrolysis, fluorogenic RNA probe-based fluorescence, and RNA cleavage assays. Among these formats, cyclic peptides exhibited enhanced RNase A inhibitory activity compared with both Fv-antibodies and linear peptides. The influence of peptide conformation on RNase inhibitory activity was further analyzed using docking simulation. These results demonstrated that cyclization of RNase A-inhibitory CDR3 sequences improved inhibitory activity and supported the development of cyclic peptide-based RNase A inhibitors.

Patients with severe infectious diseases may require admission to intensive care units (ICUs) when the infection progresses to severe forms, as observed in sepsis or, more recently, in COVID-19. Despite advances in critical care, the risk of progression toward severe or fatal outcomes remains difficult to predict, highlighting the need for reliable prognostic biomarkers. Immunoglobulin G (IgG) N-glycosylation has emerged as a key modulator of immune responses and may represent a valuable biomarker for assessing disease severity. In this study, we investigated the IgG N-glycans profiles to evaluate their potential association with clinical outcome in critically ill patients with sepsis or COVID-19. Serum IgG N-glycans were characterized using online hydrophilic interaction liquid chromatography (HILIC) solid-phase extraction, followed by HILIC separation and fluorescence and mass spectrometry detection. The study cohort included healthy controls, ICU patients with sepsis or severe COVID-19, the latter being further stratified according to survival outcome. Distinct IgG N-glycosylation patterns and relative abundances of specific N-glycan structures in serum were associated with disease etiology (sepsis versus COVID-19) as well as with patient outcomes for COVID-19 group. These findings suggest that IgG glycosylation profiling may provide a promising approach for stratifying ICU patients according to their risk of developing severe or fatal diseases.

Effects of dietary chitosan oligosaccharides on the laying performance, egg quality and serum biochemical parameters of aged laying hens.

Expansion and CAR engineering of granulocyte-monocyte progenitors for cellular immunotherapy.

Diarrhea is characterized by excessive intestinal secretion and motility, often linked to inflammatory activation. Although synthetic antidiarrheal drugs are effective, their prolonged use can cause side effects, underscoring the need for safe, natural alternatives.This study investigated the antidiarrheal and anti-inflammatory activities of Bacillus subtilis DKU_09-fermented soybean (FS) powder in a mouse model of castor oil-induced diarrhea.Male ICR mice were orally administered FS (100, 200, or 300 mg/kg) for 7 days before the induction of diarrhea with castor oil. Diarrheal onset, frequency, fecal water content, and gastrointestinal (GI) transit were recorded. Inflammatory mediators in the small intestine were analyzed using real-time polymerase chain reaction and Western blotting, while serum immunoglobulin A (IgA) and immunoglobulin G (IgG) were measured by enzyme-linked immunosorbent assay.Pretreatment with FS significantly delayed the onset of diarrhea (FS200: 132.0 ± 9.8 min vs. castor oil-treated control [DC]: 76.9 ± 5.6 min, P < .05) and reduced diarrheal frequency (FS200: 32.9 ± 5.4% vs. DC: 51.9 ± 6.1%, P < .05). FS normalized the accelerated GI transit and markedly suppressed intestinal inflammation. The expression of Il-1β, Cox-2, mPGES-1, and NF-κB (p65) mRNA was significantly decreased by FS, accompanied by inhibition of mitogen-activated protein kinase (MAPK) phosphorylation (ERK, JNK, and p38). Serum IgG and IgA levels were unaffected, indicating that the effects were localized to intestinal tissue.Soybeans fermented by B. subtilis DKU_09 exert potent antidiarrheal effects through suppression of the NF-κB/Cox-2/PGE2 and MAPK signaling pathways, thereby reducing intestinal inflammation and motility. These findings suggest that the FS used in the present study may serve as a safe and natural functional food for the management of acute diarrhea.

BackgroundCoronary angiography induces oxidative stress through contrast media exposure and ionizing radiation, potentially contributing to vascular and renal injury. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exert antioxidant and anti-inflammatory effects beyond glycemic control. We investigated whether a single pre-procedural dose of empagliflozin modulates oxidative stress and inflammatory glycosylation patterns in non-diabetic patients undergoing elective coronary angiography.MethodsIn this prospective, randomized, double-blind study, 60 patients undergoing elective coronary angiography were assigned to standard care or empagliflozin 10 mg administered 2 h before the procedure. Blood samples were collected at baseline, 4 h, and 24 h post-procedure. Total antioxidant capacity (TAC), oxidative DNA damage (alkaline comet assay), and N-glycosylation profiles of immunoglobulin G (IgG) and total plasma proteins were analyzed. Longitudinal changes were assessed using mixed-effects models with correction for multiple testing.ResultsBaseline characteristics and procedural variables were comparable between groups. Empagliflozin administration was associated with attenuation of oxidative DNA damage 24 h after angiography and stabilization of antioxidant capacity compared with standard care. Directional shifts in IgG N-glycosylation toward a less pro-inflammatory profile were observed in the intervention group, including reduced agalactosylated and core-fucosylated glycans and relative preservation of galactosylated structures. Similar modulatory trends were detected in total plasma protein glycosylation patterns. Although several glycomic changes did not reach statistical significance after correction for multiple testing, the overall biological signal consistently favored reduced oxidative and inflammatory activation in the empagliflozin group.ConclusionsA single pre-procedural dose of empagliflozin was associated with attenuation of oxidative stress-related DNA damage and modulation of inflammatory glycosylation patterns following coronary angiography. These findings suggest a potential peri-procedural cytoprotective role of SGLT2 inhibition that warrants confirmation in larger studies.Trial registrationISRCTN11022820. Registered 13 October 2025. Retrospectively registered.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s40842-026-00304-5.

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of multiple sclerosis (MS). Elevated immunoglobulin G (IgG) titers against EBV nuclear antigen 1 (EBNA1) represent the most consistent serological marker of MS risk, with levels remaining persistently elevated following disease onset. We conducted high-dimensional profiling of virus-specific antibody-associated immune features in 60 individuals with relapsing-onset MS followed over time and in 54 age- and sex-matched EBV-seropositive healthy controls. EBNA1-specific IgG in MS patients exhibited a distinct proinflammatory Fc signature, characterized by increased affinity for Fc γ receptors (FcγRs) and enhanced Fc-mediated effector functions, including antibody-dependent phagocytosis, complement activation, and natural killer cell engagement. This signature was not observed for antibodies against other common viral antigens and showed a strong association with MS. Increased FcγR binding by IgG, specific for both EBNA1 and the lytic EBV glycoprotein 350 (EBV-gp350) correlated with disease activity, defined as clinical relapse and/or presence of contrast-enhancing brain lesions (CELs). Both fragment antigen-binding and pro-inflammatory functional Fc-mediated features contribute to the association between EBNA1-specific antibody responses and MS. Fc effector functions of EBV-specific antibodies may actively participate in promoting focal disease activity in MS. ANN NEUROL 2026.

The incidence rate of idiopathic membranous nephropathy (IMN) has been increasing, and its pathogenesis is still unclear. Exploring new diagnostic molecular markers and the molecular mechanisms of IMN. Fifteen healthy controls and fifteen IMN patients were recruited. Clinical baseline data of all participants, including age, gender, and body mass index (BMI), along with histopathological staging (Ehrenreich-Churg classification) and immunohistochemical staining results for phospholipase A2 receptor (PLA2R), were collected and analyzed. Meanwhile, peripheral blood and urine samples were obtained to detect renal function-related biochemical indicators, including serum creatinine (Scr), estimated glomerular filtration rate (eGFR), serum albumin, 24-hour urinary protein (24h UPT), serum total cholesterol (TC), anti-PLA2R antibody titer, and serum immunoglobulin G (IgG). Urine samples (n = 10) were also used for high-throughput sequencing analysis. Serum albumin was significantly downregulated in the IMN group, while 24h UPT, TC, anti-PLA2R Ab titer, and IgG were upregulated. MicroRNA (miRNA) transcriptomic analysis identified 34 differentially expressed (DE) miRNAs. Hsa-miR-576-3p, hsa-miR-766-5p, and NovelmiRNA-837 exhibited strong diagnostic potential via ROC curve analysis (AUC > 0.8). Sixty-four DE mRNAs were identified in IMN tissues, with enrichment in pathways such as Ribosome and MAPK signaling-fly. ENST00000481739 (RXRA) was upregulated in IMN, correlated with anti-PLA2R Ab titer, and exhibited diagnostic potential (AUC = 0.929). Thirty-five DE lncRNAs were identified in IMN, enriched in autophagy, mitophagy, and apoptosis pathways. TCONS_00180924, TCONS_00176280, TCONS_00208611 correlated significantly with TC, 24-h urinary protein, and anti-PLA2R Ab titer. This study provides a foundation for developing non-invasive diagnostic tools and targeted therapies for IMN.

Chikungunya virus (CHIKV) is an emerging arbovirus that causes major morbidity in tropical regions, but its epidemiology in Southern Africa is poorly defined. This study compiles research on CHIKV circulation, clinical characteristics, and surveillance strategies in the region, specifically in the Southern African Developing Community (SADC) block. A systematic search of peer-reviewed publications published between January 2012 and October 2025 that reported CHIKV detection, seroprevalence, or clinical symptoms in eight Southern African countries was conducted. Eligible studies included human studies, outbreak investigations, population-based surveys, diagnostic evaluations, and case reports. Whilst, zoonotic studies, animal studies, letters to editors, comments, and studies not clearly define in terms of country, number participants and method of investigation were considered ineligible. Twenty studies met inclusion criteria, representing data from Madagascar, Mozambique, the Democratic Republic of the Congo (DRC), Angola, Tanzania, Malawi, South Africa (SA), and Mauritius. CHIKV circulation was confirmed in both urban and rural settings, often co-occurring with dengue, Zika, and Rift Valley fever viruses. Seroprevalence estimates varied widely, from sporadic detection in Angola to sustained immunoglobulin G (IgG) positivity in Madagascar and Tanzania, indicating ongoing endemic transmission. Women of reproductive and working age were disproportionately affected. Clinical presentations were dominated by acute febrile illness with arthralgia, though severe neurological outcomes and long-term rheumatologic sequelae were reported. Diagnostic practices relied primarily on serology, with molecular confirmation limited to outbreak contexts. Vector surveillance detected CHIKV in mosquitoes even in the absence of human cases. CHIKV is a common virus in Southern Africa that is not well known. Effective response and early detection depend on strengthened integrated surveillance that combines entomological, molecular, and serological approaches. The findings highlight the necessity of investigating the long-term effects of Chikungunya infection and conducting coordinated regional monitoring.

Melatonin not only regulates circadian rhythms in animals but also supports reproductive health through its potent antioxidant properties and immunomodulatory effects. In this study, the effects of exogenous melatonin administration on blood total antioxidant status (TAS), total oxidant status (TOS), Immunoglobulin G (IgG), Immunoglobulin M (IgM), and prolactin (PRL) concentrations, as well as on pregnancy rates and litter size, were investigated in rabbits. A total of 26 New Zealand rabbits were divided into two groups for the study. Melatonin implants were administered subcutaneously (SC) to group 1 (n=13) (MEL). Saline injections were administered to group 2 (n=13) (CON). Samples were collected from all rabbits before mating, on the 15th day of gestation and after parturition from the ear marginal vein and TAS, TOS, IgG, IgM, PRL concentrations and hemogram parameters were analyzed. Pregnancy rates were 77% and 92.3% in the CON and MEL groups, respectively, while litter sizes were 5.2 and 6 in the CON and MEL groups, respectively. TOS levels were found to be statistically lower (p<0.05) in the MEL group compared to the CON group just after parturition; however, there was no statistical difference between the groups in terms of TAS values at different times (p>0.05). IgG and IgM levels before mating and after parturition did not differ statistically significantly between the experimental groups when melatonin was administered. However, a statistically significant increase in the levels of both IgG and IgM was observed in the MEL group on day 15 of gestation. Exogenous melatonin administration did not alter reproductive parameters in New Zealand rabbits; however, it exhibited immunomodulatory effects on the 15th day of gestation and reduced oxidative stress after parturition.

To investigate integrated biochemical and glycomic signatures in humans related to coordinated metabolic and endocrine adaptations during prolonged fasting, which are essential for maintaining systemic homeostasis. This single-arm longitudinal interventional study enrolled five healthy adults who underwent a 72-hour water-only fast. Blood samples were collected at baseline (T0), immediately after fasting (T1), and after 11 days of refeeding (T2). A broad panel of biochemical, hormonal, inflammatory, and glycomic parameters was determined. Time-dependent differences were evaluated using the Friedman test. Fasting induced a distinct biphasic response across multiple circulating markers, with significant alterations in total cholesterol, C-reactive protein, thyroid-stimulating hormone, and free triiodothyronine at T1 followed by recovery toward baseline at T2. Insulin and glucose concentrations declined during fasting and increased after refeeding, although these changes did not reach statistical significance. Plasma, immunoglobulin G (IgG), and IgA N-glycosylation profiles were extensively remodeled, which indicated dynamic metabolic and immune system adaptation. Liver enzymes, electrolytes, and most lipid fractions exhibited only minor and reversible fluctuations. A 72-hour fast was associated with metabolic and hormonal changes consistent with an environment conducive to autophagy, although autophagy was not measured directly. The protocol appeared feasible and well tolerated in a small cohort of healthy adults. Given the limited sample size, these findings should be considered preliminary and require confirmation in larger studies incorporating direct autophagy markers and additional time points.

Autoimmune hepatitis (AIH) is an uncommon condition among persons living with HIV (PLWH), and its clinical presentation may be influences by immune reconstitution and viral reactivation, potentially affecting disease course and prognosis. In this retrospective case series, we aimed to describe the clinical features, pathological findings, treatment approaches, and outcomes of PLWH diagnosed with AIH in Yunnan Province, China, with a focus on region-specific clinical features. This single-center retrospective case series included PLWH diagnosed with AIH at Yunnan Provincial Infectious Diseases Hospital between June 2017 and February 2025, based on electronic medical records. AIH was diagnosed according to the simplified International Autoimmune Hepatitis Group criteria (definite ≥ 7 points; probable ≥ 6 points), with cases lacking liver biopsy classified as probable AIH. PLWH with other chronic liver diseases, substantial missing data, or follow-up shorter than 15 months were excluded. Among the eight PLWH, seven were female, with a median age of 46.5 years (IQR 39-51). All PLWH had been living with HIV for more than 5 years and were receiving antiretroviral therapy with well-controlled viral loads. Elevated transaminase and immunoglobulin G (IgG) levels were observed in all cases, and four of them presented with jaundice. All cases tested positive for ANA and ASMA autoantibodies; three were positive for LKM-1, two for SLA, and five for EBV-DNA (62.5%), which appeared higher than the ~ 20% reported in the general AIH population. Three PLWH (37.5%) had concomitant autoimmune diseases, including rheumatoid arthritis, Sjögren syndrome, and hyperthyroidism. Serum IL-6 (median 18.9 pg/mL, IQR 14.7-27.8) and IL-7 (median 10.2 pg/mL, IQR 8.7-13.1) levels were elevated. Liver biopsies was performed in six cases, showing inflammatory activity grades A1-A3 and fibrosis stages F0-F4, all consistent with typical features of AIH. The remaining two cases were classified as probable AIH based on the simplified criteria. One PLWH with advanced disease (A3/F4) died early due to acute hepatic failure. Among the six PLWH who received immunosuppressive therapy, five achieved complete remission and one (complicated with Sjögren syndrome) had an incomplete response. During a follow-up of 15-24 months, no relapse was observed in PLWH who achieved complete remission, and SF-36 scores improved. In PLWH in Yunnan, China, AIH presents with complex clinical features and may be potentially associated with EBV reactivation and systemic inflammation. However, the small sample size and retrospective design preclude causal inference. Our findings support the value of early non-invasive assessment and generate a hypothesis regarding the potential role of EBV monitoring. Future multiventer prospective cohorts or randomized controlled trials are required to calidate the long-term safety and efficacy of immunosuppressive therapy.