Serum IgG Levels Research Articles

The PerioGene North study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunity

IntroductionPeriodontitis is associated with rheumatoid arthritis (RA). One hypothesis posits that this connection arises from the formation of autoantibodies against citrullinated proteins (ACPA) in inflamed gums, possibly triggered by Porphyromonas gingivalis. We previously demonstrated an increased antibody response to P. gingivalis arginine gingipains (anti-Rgp IgG), not only in individuals with severe periodontitis compared to controls, but in RA versus controls, with an association to ACPA. In the present study, we set out to further explore the relationship between anti-Rgp IgG, ACPA and periodontitis, including clinical periodontal parameters, in the large and well-characterized PerioGene North case-control study.MethodsWe measured serum levels of anti-Rgp and ACPA IgG by enzyme-linked immunosorbent assay (ELISA), in 478 patients with periodontitis and 509 periodontally healthy controls within PerioGene North. Subsequently, anti-Rgp IgG levels and ACPA status were analysed in relation to periodontitis and clinical periodontal parameters.ResultsSerum anti-Rgp IgG levels were elevated in cases versus controls (p< 0.001). However, receiver operating characteristic (ROC) curve analysis revealed that anti-Rgp IgG could not efficiently discriminate cases from controls (AUC= 0.63; 95% CI: 0.60 – 0.66). Among cases, increased anti-Rgp IgG levels associated with high periodontal inflammation and advanced alveolar bone loss (p<0.001 for both). An ACPA response was detected in 15 (3.1%) cases and 6 (1.2%) controls (p=0.033), but no association to periodontitis was evident after adjustment for age and smoking and anti-Rgp IgG levels did not differ between ACPA-positive and ACPA-negative individuals.ConclusionWe show that anti-Rgp IgG identifies a subgroup of periodontitis patients with high degree of periodontal inflammation and advanced alveolar bone loss, but we do not find support for a link between periodontitis or anti-Rgp IgG and ACPA status in PerioGene North. Given the association between anti-Rgp and alveolar bone loss, the mechanistic role of gingipains in bone resorption should be experimentally explored.

Immunoglobulin G4 related sclerosing disease mimicking a lytic lesion of the mandible: a case report and review of literature.

Immunoglobulin G4 related disease (IgG4-RD) is an immune-mediated, multifocal, fibroinflammatory disease with varied clinical manifestations. The involvement of head and neck region is infrequent. The objective was to report a case of localized IgG4-RD of mandible that clinically mimicked a lytic lesion. A 22 year old female presented with restricted mouth opening and swelling over right ramus and angle region of mandible. Radiographic imaging showed an ill-defined radiolucent lytic lesion infiltrating adjacent muscles. An incisional biopsy was performed and histopathological picture was suggestive of benign spindle cell neoplasm. Immunohistochemistry was suggestive of IgG4-RD involving mandible adjoining soft tissues. Elevated serum IgG4 levels were noted. Oral steroid therapy was initiated and tapered without maintenance dose. The patient progressed without any sequelae. Imaging 2 years after completion of treatment showed complete resolution of the radiolucent lesion. The precise diagnosis of this lesion is challenging and depends on many different factors. A non-specific localized lesion should be investigated as a systemic condition. Early diagnosis and prompt initiation of steroid therapy should be favored. Continued follow up is critical due to the indolent nature of this disease. The future of management of this disease is the development of specific diagnostic criteria and targeted therapy of head & neck lesions.

Idiopathic multicentric Castleman disease diagnosed after lower extremity venous thrombosis mimicking immunoglobulin G4-related disease - A case report.

It is difficult to distinguish idiopathic multicentric Castleman disease (iMCD) from immunoglobulin G4-related disease (IgG4-RD). A 47-year-old man was diagnosed with venous thrombosis in the right lower extremity. Multiple lymphadenopathies and splenomegaly were incidentally detected. His serum IgG4 levels were high, and the biopsied lymph nodes showed high plasma cell infiltration with many IgG4-positive cells between the follicles. He was initially diagnosed with IgG4-RD and was administered prednisolone 30 mg/day; however, inflammation and IgG4 persisted. The patient was rediagnosed with iMCD and treated with tocilizumab, which led to an improvement of his condition. When diagnosing IgG4-RD, it is therefore important to consider iMCD in the differential diagnosis.

Generation and validation of antibody 42B1 recognizing galactose-deficient IgG for diagnosis of chronic inflammatory diseases.

Galactose-deficient (agalactosyl) IgG is significantly increased in the serum of patients with rheumatoid arthritis, and autoantibodies against it are used in clinical tests. Subsequent studies also show increased agalactosyl IgG in many chronic inflammatory diseases. In this study, we generated antibody 42B1 recognizing agalactosyl IgG and developed a new method to evaluate chronic inflammatory diseases with it. Using an ELISA with antibody 42B1, we measured serum levels of agalactosyl IgG in 32 patients with inflammatory bowel disease (IBD), 60 patients with chronic liver disease, 60 patients with chronic pancreatitis, and 32 subjects undergoing health checkups who did not have IBD. Serum agalactosyl IgG levels were increased in all patients with chronic inflammations and partially correlated with clinical parameters. Among the subjects undergoing health checkups, some subjects showed a 15% elevation of serum agalactosyl IgG levels, suggesting possible latent chronic inflammation. Future studies will examine the 42B1 antibody ELISA in various autoimmune diseases. Altogether, the 42B1 antibody for determination of serum agalactosyl IgG levels is a novel diagnostic tool for chronic inflammation.

Oral-Delivery Lactococcus lactis Expressing mCherry Fusion Lactoferrin Peptides against Infection of Avian Pathogenic Escherichia coli in Chickens

Avian pathogenic Escherichia coli (APEC) infections result in significant economic losses and reduced animal welfare. Historically, antibiotics and vaccinations currently control APEC infections in poultry, however, antibiotic-resistant strains and heterologous serotypes limit their effectiveness. Meanwhile, antibiotic-resistant strains can be transmitted to humans via contact with animals, food or their environment. Probiotics and antimicrobial peptides (AMPs) are potential alternatives to antibiotics and represent promising strategies to combat APEC. Bovine lactoferricin and lactoferrampin possess anti-bacterial, anti-inflammatory, and anti-oxidant properties. Lactococcus lactis (L. lactis) is an excellent vector for delivering recombinant proteins. In this research, we generated a recombinant L. lactis strain MG1363 expressing lactoferrin peptides, which was labeled with a fluorescent marker mCherry and lacked an antibiotic resistance gene (LL-EFLmC). Our investigation focused on the impact of LL-EFLmC strain on the gut microbiota composition and avian pathogenic E. coli O78 challenge. Our findings indicate that LL-EFLmC exhibits inhibitory effects against APEC-O78 and Staphylococcus aureus CVCC26003 (S. aureus CVCC26003) in vitro. Furthermore, the inclusion of LL-EFLmC in chicken feed significantly improved the average daily intake and gain to feed ratio. Additionally, LL-EFLmC treatment resulted in a significant increase in serum IgG and intestinal mucus SIgA levels. Administration of LL-EFLmC was found to effectively suppress APEC-O78 infection and mitigate the expression of pro-inflammatory cytokines, including IL-1β, IL-12, IFN-γ, and TNF-α. Additionally, 16S rDNA sequencing data revealed that LL-EFLmC was able to restore the intestinal flora that had been disrupted by APEC-O78. These findings suggest that LL-EFLmC may serve as a promising feed additive and antibiotic alternative in chicken production, due to its potential to enhance immune regulation, promote growth, and confer resistance against APEC-O78 infection.

Literature review and case study of recurrent EPGA with elevated IgG4 and positive HBsAg successfully treated with rituximab

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of autoimmune vasculitis. The involvement of IgG4 and HBsAg in EGPA is less common but can occur and may present unique challenges in management. Case presentation: We present a case study of a 70-year-old female diagnosed with EGPA confirmed via renal biopsy. She initially presented with recurrent purpura, diarrhea and progressive numbness in the hands and feet, accompanied by general weakness. Complete remission was achieved with a one-year course of prednisone acetate and cyclophosphamide treatment. However, upon discontinuation of self-medication, the disease relapsed, manifesting as a generalized rash and weakness in the extremities. Skin biopsy revealed eosinophil infiltration, with inflammatory cells predominantly surrounding blood vessels. Notably, during treatment, the patient’s hepatitis B markers transitioned from negative to positive for HBsAg. Subsequent administration of entecavir, along with monitoring for a decrease in HBV DNA levels, preceded the initiation of steroids and rituximab to attain remission once more. Among the remaining 15 patients analyzed, all exhibited elevated serum IgG4 levels, with none testing positive for hepatitis B. Notably, only one patient was diagnosed with immunoglobulin G4-related disease (IgG4-RD), suggesting that elevated IgG4 levels alone may not necessarily indicate IgG4-RD. Conclusions Our case report highlights the first instance of recurrent EGPA accompanied by elevated IgG4 and positivity for hepatitis B, which was successfully treated with rituximab. In cases of concurrent hepatitis B, rituximab treatment may be considered once viral replication is under control. However, emphasis on maintenance therapy is crucial following the induction of disease remission.

Phenotypes of primary sclerosing cholangitis in children

Background. Primary sclerosing cholangitis (PSC) in children is a rare chronic immune-mediated disease of the biliary tract, which, unlike in adults, has a less aggressive course with da­mage to the intrahepatic bile ducts and is combined with autoimmune hepatitis, creating a special clinical phenotype of PSC, autoimmune sclerosing cholangitis (ASC). Although immunosuppressive therapy is effective in controlling autoimmune inflammation, it does not inhibit the progression of fibrotic changes around the bile ducts, which, unfortunately, leads to the formation of biliary cirrhosis of the liver. Research aimed at studying the clinical course of PSC in children and improving early diagnosis is relevant, especially given the limited access to modern diagnostic methods, such as magnetic resonance cholangiopancreatography, the need for invasive studies, and the lack of standardized diagnostic criteria adapted to childhood, which complicates the diagnosis and treatment of these patients. Objective: to investigate the clinical features of primary sclerosing cholangitis in children and adolescents depending on di­sease phenotype with the aim of develo­ping individualized treatment approaches. Materials and methods. Retrospective and prospective analysis of the clinical course of primary sclerosing cholangitis in children and adolescents who were treated and followed at the Department of Pediatric Hepatology from 2016 to 2024 was conducted. The study included 68 children (62 % boys and 38 % girls) with PSC aged 3 to 18 years (mean age at diagnosis was (11.0 ± 3.9) years). Of these, 38 patients (56 %) had autoimmune sclerosing cholangitis, and 30 (44 %) had isolated PSC without clinical or histological signs of autoimmune hepatitis. Results. At disease onset, 40 % of children with PSC had liver fibrosis graded F3-F4 on METAVIR, with 24 % showing cirrhosis. The most common phenotype in children with PSC was a mixed one involving both large and small bile ducts (63 %). PSC with large bile duct involvement alone was observed in 11 % of cases, 70 % of these children were diagnosed with cirrhosis. Small duct involvement alone was present in 26 % of cases, with cirrhosis in 12.5 % (p = 0.01). Inflammatory bowel disease (IBD) was diagnosed in 84 % of children with PSC: 32 % had ulcerative colitis, 38 % had indeterminate IBD, and 16 % had Crohn’s disease. Pancolitis occurred in 56 % of cases, while 19 % of patients had histological signs of IBD without clinical or endoscopic manifestations. Asymptomatic IBD was diagnosed in 58 % of cases. The clinical course of ASC differed from isolated PSC with significantly higher rates of anemia (47 vs. 27 %, p = 0.03), elevated serum IgG levels (23.9 vs. 12.5 g/l, р < 0.01), and higher levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin (p < 0.01 for all), non-invasive fibrosis markers (APRI, FIB-4, 2D-SWE) at onset (p < 0.01; p = 0.01; p = 0.04, respectively). Liver fibrosis F3-F4 on METAVIR was more frequently diagnosed in ASC group than in patients with isolated PSC (73 vs. 40 %, p = 0.06). Large bile duct involvement alone was found only in isolated PSC (p < 0.0009). No differences were observed between ASC and isolated PSC in terms of IBD phenotype. Conclusions. PSC in children is represented by 2 phenotypes (ASC and isolated PSC) that occur with almost equal frequency. ASC and isolated PSC have similar phenotypes of biliary and intestinal lesions, however, they differ in terms of clinical course and therapeutic approaches. Involvement of the large bile duct alone in children with PSC is associated with rapid formation of liver fibrosis and cirrhosis. PSC phenotype with involvement of small bile ducts alone has a favorable course in children. Most children with PSC exhibit the PSC-IBD phenotype. Active diagnostic search for biliary and intestinal lesions in children with PSC will facilitate the development of effective personalized approaches to treatment and monitoring, thereby improving disease prognosis.

Unveiling the link: anti-protein disulfide isomerase A3 autoantibody expression and polycystic ovary syndrome risk in euthyroid autoimmune thyroiditis women

BackgroundPolycystic ovary syndrome (PCOS) is a common complication of autoimmune thyroiditis (AIT) in women, but the underlying mechanism remains unclear. Protein disulfide isomerase A3 (PDIA3) is a ubiquitous protein. We have reported that PDIA3 autoantibody (PDIA3Ab) production results from autoimmune responses against thyrocytes, resulting in its high expression in euthyroid AIT patients. This study aimed to explore potential correlations between PDIA3Ab expression and concurrent PCOS in euthyroid AIT women.MethodsThis is a single-center cross-sectional study. All participants, who visited the First Hospital of China Medical University from April 2023 to May 2024, were assigned to four groups according to AIT and PCOS diagnostic criteria. The PDIA3Ab levels of total IgG and IgG subclasses were detected using ELISA.ResultsFrom highest to lowest, PDIA3Ab total serum IgG levels were categorized as follows: AIT-PCOS group > AIT-non-PCOS group > non-AIT-PCOS group > non-AIT-non-PCOS group Significant differences were observed between each pair of groups, except for the non-AIT-PCOS and non-AIT-non-PCOS groups. Further analysis of the subclasses of PDIA3Ab revealed that serum IgG1 levels in the AIT-PCOS and AIT-non-PCOS groups were significantly higher than those in the non-AIT-PCOS and non-AIT-non-PCOS groups. In addition, the AIT-PCOS group had significantly higher serum IgG3 levels than the other three groups. Binary logistic regression analysis revealed that the PDIA3Ab total IgG level was an independent risk factor for concurrent PCOS in euthyroid AIT women (Q4 vs. Q1: OR, 95%CI = 5.082, 1.348–19.16). Furthermore, a trend test demonstrated a titer-dependent increase in PCOS prevalence among AIT women as the PDIA3Ab total IgG level increased.ConclusionsThe expression of serum PDIA3Ab may indicate an increased risk of PCOS in euthyroid AIT women and could potentially serve as new targets for markers or immune intervention.

IgG4-related disease with epithelioid granulomas: a case and a review of the literature.

IgG4-related disease (IgG4-RD) is a systemic, immune-mediated, fibroinflammatory disorder that affects multiple organs. Histopathologically, the supportive findings of IgG4-RD include dense lymphocytic infiltrates, obliterative phlebitis, storiform fibrosis, and elevated numbers of IgG4-positive plasma cells. However, the presence of granulomatous inflammation is generally considered highly atypical, suggesting alternative diagnoses such as sarcoidosis and lymphoma. Here, we present a case of IgG4-RD involving granulomatous lymphadenopathy. Labial salivary gland biopsy findings were consistent with IgG4-related sialadenitis. Elevated serum IgG4 levels, hypocomplementemia, and abnormal imaging findings in the kidneys and pancreas indicated an association with IgG4-RD. The patient was treated with prednisolone, which resulted in a significant improvement in the serum IgG4 and complement levels and a notable reduction in lymph node swelling. Although granulomatous inflammation is rare, integrating clinical, serological, radiological, and pathological parameters can ensure an accurate assessment within the appropriate clinicopathological context.

Effects of supplemental feeding of Chinese herbal mixtures to perinatal sows on reproductive performance, immunity, and breast milk quality of sows.

The aim of this study was to investigate the impact of supplementary feeding with Chinese herbal mixtures on perinatal sows, focusing on their reproductive performance, immunity and breast milk quality. Sixty healthy pregnant sows (Large white, 4 parities) were randomly allocated into five treatment groups (n = 12 per group): the control group received a basal diet, the TRT1 group received a basal diet supplemented with 2 kg/t Bazhen powder (BZP), while the TRT2, TRT3, and TRT4 groups received a basal diet supplemented with 1 kg/t, 2 kg/t, and 3 kg/t Qi-Zhu-Gui-Shao soothing liver and replenishing blood powder (QZGSP), respectively. The trial lasted for a duration of 5 weeks, commencing from day 100 of gestation and concluding on day 21 postpartum. The results showed that supplemental feeding of 2 kg/t and 3 kg/t QZGSP to periparturient sows significantly improved reproductive performance to different degrees, as evidenced by the shortened farrowing intervals and increased average daily feed intake and milk yield. Supplemental feeding of 2 kg/t and/or 3 kg/t QZGSP significantly elevated levels of IL-4, IL-10, IgG, and IgA in sow serum while reduced levels of TNF-α and IL-1β in sow serum. In addition, supplemental feeding of 2 kg/t and 3 kg/t QZGSP to perinatal sows significantly increased the protein and fat content in colostrum and milk. Analysis of 16S rRNA gene amplicon sequencing data in colostrum and milk microbiota revealed that supplemental feeding of QZGSP to perinatal sows is influenced the composition of colostrum and milk composition in sows. Specifically, at the genus level, a decrease in the relative abundance of Escherichia-Shigella, Staphylococcus and Streptococcus was observed in the TRT3 and/or TRT4 groups on day 0 of lactation. The findings from this study indicate that supplemental feeding of 2 kg/t and 3 kg/t QZGSP significantly improved the reproductive performance, immunity and milk quality in sows. Therefore, QZGSP is a beneficial feed additive for perinatal sows.

Pancreatic volume change using three dimensional-computed tomography volumetry and its relationships with diabetes on long-term follow-up in autoimmune pancreatitis.

Several studies found that early pancreatic atrophy detected by computed tomography (CT) within 6 months was associated with a high incidence of diabetes in patients with type-1 autoimmune pancreatitis (AIP) receiving steroid therapy; however, no long-term follow-up studies have been performed. To investigate pancreatic volume (PV) changes using three dimensional (3D)-CT volumetry and their relationship with IgG4 and diabetes in patients with AIP. This retrospective study included 33 patients with type-1 AIP receiving steroid therapy. Patients were divided into diffuse (D-type) and mass-forming type (M-type) AIP. PV was determined by semi-automated 3D-CT volumetry, and changes between initial and follow-up values were calculated. The relationship between PV and serum IgG4 levels was analyzed by Spearman's rank correlation. The PV atrophy ratio compared with the presumed normal PV at the time of last follow-up CT and its relationship with diabetes were investigated. There were 16 D-type and 17 M-type patients with long-term follow-up (mean, 95.8 months). The regression curve of mean relative PV change reduced exponentially and rapidly during the first 25 months and then more slowly in both groups. The overall cumulative pancreas re-enlargement rates at 1, 3, 5, 7 and 10 years were 6.1%, 12.2%, 29.2%, 47.5% and 55.0%, respectively. There was a moderate-to-very strong positive correlation (ρ ≥ 0.4) between PV and serum IgG4 levels in nine (9/13, 69.2%) patients. All 33 patients showed pancreatic atrophy (mean 59.3%) after long-term follow-up. Patients with D-type AIP had a significantly higher atrophy rate and higher incidence of diabetes than M-type patients (P < 0.05). PV change initially reduced exponentially and then more slowly and is considered an important factor associated with diabetes. Serum IgG4 levels were positively correlated with PV during follow-up.

Relationship between pancreatic morphological changes and diabetes in autoimmune pancreatitis: Multimodal medical imaging assessment has important potential.

Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis with clinical symptoms of obstructive jaundice and abdominal discomfort; this condition is caused by autoimmunity and marked by pancreatic fibrosis and dysfunction. Previous studies have revealed a close relationship between early pancreatic atrophy and the incidence rate of diabetes in type 1 AIP patients receiving steroid treatment. Shimada et al performed a long-term follow-up study and reported that the pancreatic volume (PV) of these patients initially exponentially decreased but then slowly decreased, which was considered to be an important factor related to diabetes; moreover, serum IgG4 levels were positively correlated with PV during follow-up. In this letter, regarding the original study presented by Shimada et al, we present our insights and discuss how multimodal medical imaging and artificial intelligence can be used to better assess the relationship between pancreatic morphological changes and diabetes in patients with AIP.

Therapeutic effects and mechanisms of berberine on enteritis caused by Salmonella in poultry.

The present study aimed to investigate the therapeutic effects of berberine (BBR) on Salmonella enteritis in broiler chickens and to elucidate its mechanisms of action preliminarily. Blood samples were collected from 21- to 35-day-old Sanhuang male chicks to measure immune and biochemical indicators and to calculate the organ coefficients for the liver, spleen, bursa of Fabricius, and thymus. The caecal microbiota was analysed through 16S ribosomal RNA (rRNA) gene sequencing, and transcriptome sequencing was conducted. Compared with the positive control group (S), the berberine-treated group (BS) presented increased serum immunoglobulin M (IgM) levels, serum IgG levels, and total antioxidant capacity; berberine ameliorated the increase in the thymus index caused by Salmonella administration. The addition of berberine to the diet increased the abundance of beneficial bacterial genera, including Bacteroides and Lactobacillus. It also decreased the abundance of harmful bacterial genera, including Faecalibacterium and Streptococcus. Transcriptome analysis revealed that gene expression in the S and BS groups was associated with T cell selection and B cell receptor signalling pathways, which are enriched primarily in multiple immune-related signalling pathways, including the B cell receptor signalling pathway, NF-κ B signalling pathway, intestinal immune network for IgA production, asthma, and African trypanosomiasis. The significantly expressed genes included ATAD5, ERP29, MGST2, PIK3CA, and HSP90AA1. The present study demonstrated that berberine has a good therapeutic effect on Salmonella infection in chicks, as it inhibits the occurrence and development of Salmonella-induced intestinal inflammation by regulating the balance of the gut microbiota and the expression of related genes, including ATAD5, ERP29, MGST2, PIK3CA, and HSP90AA1.

Efficacy of ofatumumab combined with corticosteroids in the treatment of autoimmune encephalitis: a 6-month cohort study.

This study investigated the efficacy of ofatumumab (OFA) combined with corticosteroids in autoimmune encephalitis (AE) patients refractory to conventional treatment. Eighteen AE patients admitted to Ruijin Hospital between June 2022 and September 2023 received four subcutaneous 20-mg OFA injections at 0, 1, 6, and 12 weeks combined with standard corticosteroid therapy. Clinical symptoms, modified Rankin scale (mRS) scores, Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores, serum immunoglobulin (Ig) levels (IgG and IgM), and peripheral blood CD20 + B cell levels were documented before OFA administration and at 1, 2, 6, 12, and 24 weeks post-treatment. OFA treatment significantly improved psychiatric symptoms (P = 0.025), cognitive dysfunction (P = 0.008), and seizure frequency (P = 0.014). The mRS and CASE scores improved after two injections in patients with anti-NMDAR encephalitis (P = 0.041), but not in patients with anti-LGI1 encephalitis (P > 0.05). The mRS scores significantly improved at 12 weeks post-treatment in antibody-negative encephalitis. Blood CD20 + B cell levels dropped to zero after an average of 2.5 injections. No significant changes could be observed in serum IgG and IgM levels (P > 0.05). Seven patients had mild fever or pulmonary infections post-treatment. This study suggests that OFA is a safe and effective treatment for a subset of AE patients, particularly in cases of anti-NMDAR encephalitis, though further research is needed on long-term outcomes and recurrence.

Maggot alleviates imiquimod-induced psoriasis-like skin lesions in mice by inhibiting immune stress and complement activation

To explore the therapeutic mechanism of maggot for psoriasis-like lesions in mice from the perspective of immune stress and complement activation regulation. Thirty-six male C57BL/6 mice were randomly divided into control group, model group, maggot (1.25%, 2.5%, and 5%) groups, and Benvitimod (1%) group. Psoriasis-like lesions were induced by application of imiquimod cream, and the severity of skin lesions was assessed using the modified Psoriasis Area and Severity Index (MPASI) score. Auricular swelling of the mice was observed, and histopathological changes of the skin lesions were examined with HE staining. Scratching behavior of the mice was observed and the spleen index was calculated. Toluidine blue staining was used to detect mast cells in the skin lesions, and serum levels of IgG, IgM, the complements CH50, C1s, C3, C3a, C5 and C5a, and the inflammatory factors IL-23, IL-17A and TNF-α were determined with ELISA. In mice with imiquimod-induced psoriasis-like skin lesions, treatment with the maggot at the 3 doses significantly decreased MPASI score, alleviated auricular swelling and pathologies in the skin lesions, reduced scratching behaviors, spleen index, and the number of mast cells in the lesions. Treatment with high-dose maggot significantly lowered serum levels of IgG, C1s, C3a, C5a, IL-23, IL-17A and TNF- α and the levels of C1s, C3, C3a, C5 and C5a in the lesion tissue, and increased serum levels of CH50, C3, and C5. The therapeutic effect of maggot showed a dose-effect dependence. Maggot can alleviate psoriasislike skin lesions in mice by inhibiting immune stress and complement activation.

Synbiotics, a promising approach for alleviating exacerbated allergic airway immune responses in offspring of a preclinical murine pollution model

Exposure to pollutants like environmental cigarette smoke (CS) poses a major global health risk, affecting individuals from an early age. Therefore, this study explores how postnatal synbiotic supplementation affects allergic asthma symptoms in house-dust-mite (HDM)- challenged offspring maternally exposed to CS. In HDM-allergic offspring of CS-exposed dams, lung resistance was elevated, but synbiotic supplementation effectively reduced this resistance. Elevated eosinophil BALF counts following HDM challenge were intensified in pups maternally exposed to CS. Similarly, Th2 cell activation and serum IgE and IgG1 levels were more pronounced in HDM-allergic offspring of CS-exposed mothers. Synbiotics reduced eosinophil numbers and serum IgE and IgG1, and tended to decrease Th2 cell infiltration and activation. Synbiotics promoted beneficial gut bacteria like Bifidobacterium and Akkermansia. In conclusion, early-life synbiotic intervention mitigated allergic asthma associated with maternal air pollution exposure, highlighting the potential of synbiotics for clinical evaluation as a strategy to prevent allergy development in offspring.

Protective effect of Curcuma longa L. leaves and pseudostems extract against 1-chloro-2,4-dinitrobenzene-induced atopic dermatitis in BALB/c mice

Ethnopharmacological relevanceThe perennial herbaceous plant, Curcuma longa L. (turmeric) is primarily grown and harvested for pharmacological purposes in China, Korea, and various tropical regions in South Asia. Turmeric has been used for centuries as an indigenous medicine. In particular, Ayurveda has been extensively used to treat, prevent, and manage multiple illnesses, including inflammation, allergies, arthritis, cancer, diabetes, diarrhea, psoriasis, and digestive issues. Importantly, various studies have confirmed the presence of numerous active compounds with health-enhancing biological properties in turmeric leaves and pseudostems. Aim of the studyAtopic dermatitis (AD) is a long-lasting inflammatory disorder that is associated with abnormalities in the immune system, such as T-helper (Th) cell dysregulation, elevated immunoglobulin (Ig) levels, inflammatory cell infiltration, and skin barrier damage. This study aimed to explore the therapeutic effects of turmeric leaves and pseudostems (CLHW) extract against AD in a BALB/c mouse disease model established using 1-chloro-2,4-dinitrobenzene (DNCB). Materials and methodsAD-like symptoms were induced by topically applying DNCB to the dorsal skin of the mice, which were monitored over five weeks. Fourteen days after induction, the mice were randomly divided into different groups, and the treatment groups received daily oral gavage of CLHW for three weeks. Throughout the monitoring period, we assessed AD-like symptoms, including skin severity score, transepidermal water loss (TEWL), and scratching behavior of the mice. After measuring the body weight and ear thickness, the mice were euthanized. Furthermore, serum Ig and cytokine production levels were measured. Finally, the degrees of spleen and lymph node enlargement were evaluated, and the tissues were used for histopathological and molecular analyses. ResultsCLHW improved AD-like symptoms, including skin severity score, TEWL, scratching frequency, and ear thickness in DNCB-induced AD mice. Additionally, serum levels of IgE, IgG1, and IgG2a, along with various inflammatory cytokines (interleukin [IL]-4, IL-5, and IL-13) and chemokines (Eotaxin and RANTES), were significantly reduced in CLHW-treated mice. CLHW decreased inflammatory cell infiltration and mast cell degranulation while downregulating mRNA expression levels of AD-related innate cytokines (thymic stromal lymphopoietin [TSLP], IL-25, IL-33), inflammatory cytokines (IL-4, IL-10, IL-13), and chemokines (thymus and activation-regulated chemokine [TARC], macrophage-derived chemokine [MDC]) in the dorsal skin. Furthermore, CLHW reduced spleen and lymph node enlargement and downregulated mRNA expression levels of inflammatory cytokines in these tissues in a dose-dependent manner. ConclusionThe results demonstrated that CLHW can effectively suppress DNCB-induced AD-like symptoms by reducing the skin severity score, TEWL, scratching, ear thickness, serum Ig levels, inflammatory cell infiltration, and degranulation of mast cells, as well as the enlargement of the spleen and lymph nodes. Our findings highlight the ethnopharmacological potential of CLHW for treating abnormal immune responses associated with AD.

Extraction and Identification of Polysaccharide from Lentinus edodes and Its Effect on Immunosuppression and Intestinal Barrier Injury Induced by Cyclophosphamide.

Lentinus edodes serves as a significant source of both medicine and food, with its key component, lentinan (LNT), recognized as an effective immunomodulator. However, the mechanisms by which it regulates immune and intestinal functions under conditions of immunosuppression remain unclear. This study aims to investigate the components of lentinan and examine its potential effects on countering cyclophosphamide (CP)-induced immunosuppression, intestinal barrier damage, and dysregulation of gut microbiota. In this study, the effects of LNT were evaluated by serological indicators, histopathological changes in ileum, tight-junction-related protein expression, cytokine expression levels, and gut microbiota 16S rRNA gene sequencing. We found that LNT was effective in mitigating the abnormalities in body weight, immune organ index, and serum levels of IL-6, IL-2, IFN-γ, and IgG in mice induced by CP (p < 0.05). Furthermore, LNT demonstrated the ability to alleviate intestinal barrier damage induced by CP by increasing the mRNA levels of TNF-α, IL-1β, IFN-γ, Occludin, and ZO-1 (p < 0.05). Additionally, 16S rRNA gene sequencing revealed that LNT also normalized the disrupted abundance of Firmicutes, Proteobacteria, and Bacteroidets caused by CP. This restoration brought the gut microbiota back to normal levels and increased the abundance of certain tumor-inhibiting bacteria, such as Alistipes. Overall, lentinan demonstrated the ability to reverse the immunosuppressive effects induced by cyclophosphamide and modulate gut microbiota to restore a healthy microbial balance.

CT Coronary Angiogram in Diagnosing IgG4 of Coronary Arteries Presenting as Acute Coronary Syndrome: A Case Report with Literature Review

AbstractImmunoglobulin G4-related disease (IgG4 RD), first described in 2001, as a case of autoimmune pancreatitis, is a multisystemic condition, involving the salivary glands, bile ducts, pancreas, retroperitoneal organs, and mesentery and is associated with raised level of serum IgG4. Reports of coronary involvement by IgG4 RD are scarce and we could find only 16 case reports in the literature. Here, we present a case of a 61-year-old lady, with no known comorbidities, who presented with rapid progression of coronary artery stenosis. Initially, she presented with mild stenosis of left anterior descending which rapidly progressed to significant triple vessel disease in 3 months. Serological workup for antibodies was negative, except for raised serum IgG4 antibodies. She was managed effectively with steroids.

IFN-associated B cell hyperactivity is highly enriched in SLE patients harboring Sm/RNP antibodies.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by an array of autoantibodies, in particular anti-nuclear antibodies (ANA). The disease is also hallmarked by an expansion of plasmablasts (PB) in peripheral blood. How these relate to autoantibody production is not clear. Here, we aimed to understand B cell alterations in SLE and their relationship to immunoglobulin levels and autoantibody production. We demonstrate that a subgroup of SLE patients is characterized by a high frequency of PB relative to memory B cells (high PB/M). Patients with this phenotype more frequently had high disease activity. Despite low overall frequencies of memory B cells, these patients exhibited an increased activation in the switched CD27+ memory compartment and a strong IFN signature in PB. Repertoire analysis revealed a highly polyclonal expansion and enrichment for IgG1 expressing PB in patients with a high PB/M ratio which was reflected in increased serum IgG levels. Importantly, the hyperactive B cell phenotype was highly enriched in patients harboring Sm/RNP autoantibodies (OR: 9.17 (2.97-26.0)). In summary, we show for the first time a direct relationship between IFN and PB expansion in a subgroup of SLE patients, highly enriched in those harboring Sm/RNP antibodies. These results provide insight into the pathways leading to B cell hyperactivity and autoantibody production which may guide the tailoring of B cell- and IFN-targeted therapies.