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1.
Article in English | MEDLINE | ID: mdl-38715896

ABSTRACT

Immunoglobulin G4 (IgG4)-related diseaseis a systemic inflammatory condition of unknown etiology characterized by increases in serum IgG4 and in the number of IgG4-positive cells in affected tissues. One of the commonly involved locations is the pancreas; this condition is known as type 1 autoimmune pancreatitis (AIP). Type 1 AIP, which shows a biliary stricture in the intrapancreatic bile duct, can be misdiagnosed as a malignancy due to similar cholangiography findings and clinical presentation. In rare cases complicated by post-bulbar duodenal ulcers, differentiating between type 1 AIP and malignancies is even more difficult. An 81-year-old male was referred to our hospital for the treatment of a pancreatic head mass and obstructive jaundice. Serological and radiological findings were consistent with both type 1 AIP and a malignancy. Gastroduodenoscopy revealed a post-bulbar duodenal ulcer with endoscopic features that evoked malignant duodenal invasion. Although biopsies were negative for malignant cells, subsequent bleeding from the lesion suggested the progression of malignancy, which led to surgical resection. Pancreatoduodenectomy and pathological examination indicated that type 1 AIP was present. Simultaneously, the involvement of IgG4-related disease in the ulcerative lesion was suggested. To our knowledge, this is the first reported case of type 1 AIP complicated by post-bulbar duodenal ulcers, which was misdiagnosed as malignancy and considered an IgG4-related gastrointestinal disease associated with type 1 AIP.

2.
J Investig Med High Impact Case Rep ; 12: 23247096241286368, 2024.
Article in English | MEDLINE | ID: mdl-39369317

ABSTRACT

Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan, fibro-inflammatory condition that presents with painless organ swelling, lymphoplasmacytic infiltration, and obliterative phlebitis, often showing a favorable response to corticosteroid therapy. The most affected organs include the pancreas, kidneys, retroperitoneum, lacrimal glands, and salivary glands. Diagnosis relies on serological, imaging, and histopathological findings, with glucocorticoids as the primary treatment. Despite its reversible nature and good prognosis in many cases, long-term complications such as organ dysfunction or malignancy can still occur. International collaborative efforts have enhanced the understanding, diagnosis, and management of IgG4-RD, emphasizing the importance of comprehensive diagnostic criteria and appropriate therapeutic strategies. Herein, we present an interesting case of a geriatric male who was referred to our clinic because of concern for pancreatic cancer. We diagnosed the patient with autoimmune pancreatitis, a manifestation of IgG4-RD. The patient experienced a dramatic response to steroid therapy and is currently on maintenance therapy.


Subject(s)
Autoimmune Pancreatitis , Immunoglobulin G4-Related Disease , Humans , Immunoglobulin G4-Related Disease/complications , Immunoglobulin G4-Related Disease/drug therapy , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/pathology , Male , Autoimmune Pancreatitis/drug therapy , Aged , Glucocorticoids/therapeutic use , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/drug therapy , Tomography, X-Ray Computed , Immunoglobulin G/blood
3.
Front Immunol ; 15: 1376723, 2024.
Article in English | MEDLINE | ID: mdl-39364411

ABSTRACT

Primary Sjögren's syndrome (pSS) is an autoimmune disease, with B cell hyperactivation and autoantibody production as its immunological hallmarks. Although the distinction between immunoglobulin G4-related disease (IgG4-RD) and pSS, based on the presence or absence of certain autoantibodies, seems easy to make, possibility of elevated serum IgG4 concentration and often similar organ involvement may lead to a misdiagnosis. The increased serum concentration of IgG4 in IgG4-RD is not clearly linked to the pathogenesis of IgG-RD and it has been suggested that it may constitute just an epiphenomenon. The aim of this article is to discuss the presence of IgG4 in pSS and IgG4-RD and its potential significance for these two diseases.


Subject(s)
Immunoglobulin G4-Related Disease , Immunoglobulin G , Sjogren's Syndrome , Sjogren's Syndrome/immunology , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/blood , Humans , Immunoglobulin G/immunology , Immunoglobulin G/blood , Immunoglobulin G4-Related Disease/immunology , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/blood , Autoantibodies/immunology , Autoantibodies/blood , Biomarkers/blood
4.
Sci Rep ; 14(1): 23138, 2024 10 04.
Article in English | MEDLINE | ID: mdl-39366976

ABSTRACT

The antigen-mediated B cell isolation method, based on the detection of surface IgG (sIgG), has increased the efficiency of therapeutic antibody (Ab) discovery. However, the reduction in sIgG expression on B cells during plasma cell differentiation presents challenges as it enables Ab production from only a small subset of B cells (e.g., memory B cells). The present study aimed to addressed this problem by developing a workflow to isolate human-IgG-secreting hybridoma cells produced by cell fusion, the majority of which express sIgG. We showed that our sIgG-based antigen-coated bead separation method efficiently enriched hybridoma cells expressing antigen-specific Abs with a yield of 83.5% (from the cell fusion pool) and a positive rate of 73.2%. Furthermore, because the separation could be performed after only a short (1-2-day) culture period following cell fusion, diverse hybridoma clones could be obtained, minimizing clonal selection and the incidence of duplicates. Given that the expression of membrane-bound IgG and sIgG are regulated by different splicing mechanisms, we speculate that the cell fusion step potentially attenuated the suppression of human sIgG expression. Overall, our proposed method is expected to markedly improve the efficiency of therapeutic Ab candidate production, which will have important clinical implications.


Subject(s)
Hybridomas , Immunoglobulin G , Workflow , Hybridomas/metabolism , Hybridomas/immunology , Humans , Immunoglobulin G/immunology , Animals , Cell Separation/methods , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , B-Lymphocytes/cytology , Mice , Cell Fusion/methods
5.
Encephalitis ; 4(4): 87-90, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39397529

ABSTRACT

Immunoglobulin G4 (IgG4)-related disease is an immune-mediated, fibroinflammatory condition that causes multisystemic contrast enhancement and is predominantly observed in elderly male patients. The most prominent features of IgG4-related disease are systemic involvement affecting from two to six systems. In the central nervous system, these contrast enhancements are typically found in the meninges and orbit. This case study describes a 78-year-old female patient with persistent headaches and constant diarrhea who underwent treatment for IgG4-related disease. Despite two months of treatment with non-steroidal and opioid analgesics, the patient remained unresponsive and continued to experience diarrhea for 4 months. Brain magnetic resonance imaging revealed contrast enhancement in the leptomeningeal surfaces, and a biopsy of the gastrointestinal mucosa confirmed the diagnosis of IgG4-related disease, showing widespread plasma cell infiltration and IgG4 expression on plasma cells. The patient was initially treated with 1.0 g/day of pulse therapy for 5 days, followed by a maintenance dose of 1.0 mg/kg oral azathioprine. When azathioprine caused significant pancytopenia, rituximab therapy was initiated. The patient's headaches resolved completely, and the diarrheal attacks were controlled. This case highlights the importance of considering IgG4-related disease as a potential cause of headache or multiorgan symptoms in elderly patients with new-onset headache unresponsive to conventional analgesics. IgG4-related disease can often be effectively treated with steroids and monoclonal antibodies.

6.
Int Immunopharmacol ; 143(Pt 1): 113314, 2024 Oct 11.
Article in English | MEDLINE | ID: mdl-39395381

ABSTRACT

Gliomas are the most common malignant brain tumor in the central nervous system. They are characterized by high invasiveness and heterogeneity. In recent years, cancer-derived immunoglobulin G (Cancer-IgG) has received significant attention from researchers. Cancer-IgG, identified from tumors, can promote tumorigenesis and tumor progression. In this study, we explored the expression patterns of Cancer-IgG using available datasets and validated these patterns in our patient samples. Several loss-of-function and gain-of function assays were performed to investigate the roles of Cancer-IgG. Potential mechanisms underlying these roles were investigated using co-immunoprecipitation and RNA sequencing. Our result demonstrated that Cancer-IgG is expressed in gliomas. Furthermore, the expression of Cancer-IgG is associated with a poor prognosis and malignant molecular characterization. Functional assays confirmed that Cancer-IgG can promote glioma cells proliferation, migration, invasion, and resistant to apoptosis. The cGMP/PKG/VASP pathway is potentially involved in the effects of Cancer-IgG. Evidence from co-culture assay suggest that Cancer-IgG can induce M2 polarization of macrophages. In conclusion, Cancer-IgG can be identified in glioma cells and promotes the development of a malignant biological phenotype in vivo and in vitro. In glioma microenvironment, Cancer-IgG can induce M2 polarization of macrophages.

7.
J Rheum Dis ; 31(4): 230-243, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39355543

ABSTRACT

Objective: This study aimed to elucidate the clinical and laboratory differences between chronic sclerosing sialadenitis (CSS) and primary Sjögren's syndrome (pSS), highlighting CSS as a distinct pathological entity within the spectrum of salivary gland pathology. Methods: This retrospective, single-center study was conducted at Seoul St. Mary's Hospital between January 2000 and December 2022. Patients diagnosed with CSS via salivary gland biopsy were included, and those with IgG4-related disease (IgG4-RD) or other confounding factors were excluded. Clinical and laboratory CSS profiles were compared with those of a control group of patients with typical pSS from the Korean Initiative of Primary Sjögren's Syndrome (KISS) prospective cohort study. Twenty-one with CSS and 501 patients with pSS from Seoul St. Mary's Hospital were retrospectively analyzed. Results: Patients with CSS were older at diagnosis, had a lower prevalence of ocular symptoms, and exhibited distinct immunological markers compared to those with pSS. Logistic regression analysis revealed that anti-Ro antibody positivity, elevated erythrocyte sedimentation rate levels, low serum complement 3 levels, and accompanying dry eye symptoms were factors distinguishing pSS from CSS. Conclusion: Even after excluding IgG4-RD, CSS was significantly different from pSS in terms of clinical and laboratory findings. Recognition of these differences is crucial for the accurate diagnosis and management of CSS, underscoring its status as a distinct pathological entity among salivary gland pathologies.

8.
Immunol Rev ; 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39340138

ABSTRACT

Antibodies provide an essential layer of protection from infection and reinfection with microbial pathogens. An impaired ability to produce antibodies results in immunodeficiency and necessitates the constant substitution with pooled serum antibodies from healthy donors. Among the five antibody isotypes in humans and mice, immunoglobulin G (IgG) antibodies are the most potent anti-microbial antibody isotype due to their long half-life, their ability to penetrate almost all tissues and due to their ability to trigger a wide variety of effector functions. Of note, individuals suffering from IgG deficiency frequently produce self-reactive antibodies, suggesting that a normal serum IgG level also may contribute to maintaining self-tolerance. Indeed, the substitution of immunodeficient patients with pooled serum IgG fractions from healthy donors, also referred to as intravenous immunoglobulin G (IVIg) therapy, not only protects the patient from infection but also diminishes autoantibody induced pathology, providing more direct evidence that IgG antibodies play an active role in maintaining tolerance during the steady state and during resolution of inflammation. The aim of this review is to discuss different conceptual models that may explain how serum IgG or IVIg can contribute to maintaining a balanced immune response. We will focus on pathways depending on the IgG fragment crystallizable (Fc) as pre-clinical data in various mouse model systems as well as human clinical data have demonstrated that the IgG Fc-domain recapitulates the ability of intact IVIg with respect to its ability to trigger resolution of inflammation. We will further discuss how the findings already have or are in the process of being translated to novel therapeutic approaches to substitute IVIg in treating autoimmune inflammation.

9.
Talanta ; 282: 126949, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39341058

ABSTRACT

The efficient and accurate separation of immunoglobulin G (IgG) plays a vital role for disease diagnosis and therapy, but it is always hampered by the huge geometric size and complex structure of IgG. In this work, an amorphous Fe/Co bimetallic organic framework (denoted as PMOF-Fe/Co) is fabricated for IgG separation, with octa-carboxyl polyhedral oligomeric silsesquioxane (OCPOSS) as modulator for the first time. Benefiting from the rigid nanostructure and competitive coordination of OCPOSS, the aperture of PMOF-Fe/Co is enlarged to ∼20 nm along with the generation of enormous structural defects, which enables the accommodation of protein species with high molecular weights and large sizes. OCPOSS is also found exerting a positive impact on mediating the specific recognition and adsorption ability of PMOF-Fe/Co towards IgG through metal affinity, hydrophilic and hydrophobic interactions. Consequently, the multimode and multivalent affinity of PMOF-Fe/Co gives rise to an extraordinary adsorption capacity (2691.7 mg g-1) and satisfactory practical application performance. This study is convinced to provide a simple avenue for the efficient separation of specific large-sized proteins, as well as the engineering of abiotic affinity reagents with compositional and architectural complexity.

10.
World Allergy Organ J ; 17(8): 100940, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39247520

ABSTRACT

Antigen-specific IgG2 and IgG3 are rarely measured in food allergy clinical trials despite known function in preventing mast cell and basophil activation. Our objective was to determine whether measuring peanut-specific IgG2 and IgG3 levels would correlate with peanut allergy status. Peanut-specific IgG subclasses were measured via ELISA assays in Learning Early About Peanut allergy (LEAP) trial participants at 5 years of age and were correlated with peanut allergy vs peanut sensitization vs non-peanut allergic and peanut consumption vs peanut avoidance. Peanut-specific IgG1, IgG2, IgG3, and IgG4 levels were significantly different between participants with peanut allergy vs peanut sensitization vs non-peanut allergic, and a multivariate logistic regression model and stepwise selection found that IgG1 most closely associated with peanut allergy status. Similarly, all subclasses differentiated those consuming vs those avoiding peanut, but subsequent modeling found that IgG4 most closely associated with consumption status. Amongst the peanut-specific IgG subclasses, IgG1 was the best biomarker for peanut allergy, while IgG4 was the best biomarker for peanut antigen exposure in this highly atopic cohort. Our study did not find added value from evaluating peanut-specific IgG 2 and 3 as biomarkers of peanut allergy, although they did correlate with peanut allergy. Subsequent studies should assess the value of adding IgG subclasses to multivariate models predicting peanut allergy status.

11.
BMC Neurol ; 24(1): 318, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39237872

ABSTRACT

BACKGROUND: To report a case of IgG4-related pachymeningitis presenting with cystic lesions mimicking neurocysticercosis. CASE PRESENTATION: A 40-year-old female patient with tetraparesis, dysphagia and dysphonia was evaluated with clinical examination, magnetic resonance imaging, and meningeal biopsy. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement involving the cranial, cervical, thoracic, and lumbar segments with spinal cord compression and cystic lesions. CSF immunology was initially positive for cysticercus cellulosae. After disease progression a meningeal biopsy was compatible with IgG4 related disease. The patient had partial response to rituximab and needed multiple surgical procedures for spinal cord decompression and CSF shunting. CONCLUSIONS: This case highlights the possibility of IgG4-related disease in patients with diffuse pachymeningitis causing spinal cord compression, even with cystic lesions on MRI. Diagnosis of IgG4-related pachymeningitis is paramount due to the possibility of treatment response to immunotherapy, particularly to anti-CD20 agents.


Subject(s)
Immunoglobulin G4-Related Disease , Meningitis , Neurocysticercosis , Spinal Cord Compression , Humans , Female , Adult , Meningitis/diagnosis , Neurocysticercosis/complications , Neurocysticercosis/diagnosis , Neurocysticercosis/diagnostic imaging , Spinal Cord Compression/etiology , Diagnosis, Differential , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/complications , Magnetic Resonance Imaging , Immunoglobulin G/blood , Immunoglobulin G/cerebrospinal fluid
12.
Tex Heart Inst J ; 51(2)2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39279267

ABSTRACT

Myocarditis is a potentially life-threatening inflammatory disease of the myocardium, often resulting from infectious and immune-mediated responses. Clinical presentation in severe cases often results in a devastating illness requiring extracorporeal membrane oxygenation support as a result of cardiogenic shock. Although endomyocardial biopsy is still considered the gold standard for diagnosis, it often reveals nonspecific lymphocytic infiltration. Because the precise cause is usually unknown, the initial treatment typically involves immunosuppression and frequent assessment of myocardial contractility. This report presents 3 rare cases of autoimmune diseases (polymyositis, immunoglobulin G4-related disease, and systemic lupus erythematosus) that require extracorporeal membrane oxygenation support as a result of fulminant myocarditis, including their follow-up periods.


Subject(s)
Extracorporeal Membrane Oxygenation , Myocarditis , Humans , Myocarditis/therapy , Myocarditis/diagnosis , Myocarditis/physiopathology , Myocarditis/immunology , Extracorporeal Membrane Oxygenation/methods , Male , Female , Adult , Biopsy , Middle Aged , Autoimmune Diseases/diagnosis , Autoimmune Diseases/therapy , Autoimmune Diseases/immunology , Autoimmune Diseases/complications , Myocardium/pathology , Myocardium/immunology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/therapy , Shock, Cardiogenic/therapy , Shock, Cardiogenic/etiology , Shock, Cardiogenic/diagnosis , Treatment Outcome , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/therapy , Immunoglobulin G4-Related Disease/complications
13.
Animals (Basel) ; 14(17)2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39272365

ABSTRACT

The aim of this research was to evaluate the effects of postpartum day and parity season on the lactoferrin (LF), immunoglobulin G (IgG), and chemical composition of Murciano-Granadina goat colostrum during the first 96 h after kidding, and the use of the Brix refractometer to estimate IgG content. A herd of 3500 intensively managed Murciano-Granadina dairy goats (45-50 kg body weight) was used. Colostrum samples were collected from days 1 to 4 postpartum in the winter, spring, summer, and autumn. The colostrum composition was assessed using an automated infrared method; the LF and IgG concentrations were measured using an ELISA, and for the Brix percentage, we used a digital refractometer. Colostrum taken on the first postpartum day showed the highest concentrations of LF, IgG, proteins and non-fat solids (NFSs). As the postpartum days progressed, a rapid decrease in the LF, IgG, protein, and NFS contents and the Brix value was observed. In contrast, the lactose content increased steadily until the fourth postpartum day (p < 0.001). The season influenced milk yield, LF, IgG, protein, fat, and somatic cell content (p < 0.05). LF contents were significantly higher in the spring season, IgG contents were higher in autumn colostrum, and fat components were higher in the winter season. The colostrum Brix value showed a positive correlation with the ELISA colostrum LF (r = 0.716, p < 0.001) and IgG (r = 0.894, p < 0.001) determination; a 20 mg IgG/mL colostrum concentration corresponded to 18 °Brix. Our results corroborate the importance of feeding colostrum to newborns on the first day after birth, not only because of its high level of IgG but also because of its greater presence of the other bioactive protein compounds such as lactoferrin.

14.
Med Mycol Case Rep ; 46: 100668, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39314642

ABSTRACT

Miliary coccidioidomycosis is a severe manifestation of diseases caused by Coccidioides immitis and Coccidioides posadasii that is endemic to the southwestern United States as well as Central and South America. While most cases of coccidioidomycosis present with pulmonary disease, certain risk factors increase the risk for disseminated disease. We present a case of miliary coccidioidomycosis in a 46-year-old patient with uncontrolled diabetes. Additionally, we review the features of thirty-seven cases of patients with miliary coccidioidomycosis.

15.
J Eval Clin Pract ; 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39308303

ABSTRACT

RATIONALE: The change of IgG of COVID-19 vaccine was thought to be an effect of diet quality or daily habits. AIMS AND OBJECTIVES: This study aimed to correlate diet quality and healthy living factors with serum IgG response in the blood. METHODS: Participants were selected from volunteers who had their first vaccination and did not have COVID-19 disease (Male = 21 Female = 40). Serum IgG levels were measured on average (avg) 28 days after the COVID-19 vaccine. Information was obtained directly from the participants by questionnaire method (Food consumption record, frequency of food consumption, Diet Quality Index [(DQI], etc.). RESULTS: A significant difference was observed in the IgG levels of the second measurement of age (young/middle) and gender (male/female) (p < 0.05). A significant difference was found in the first measurement of serum IgG levels and IgG avgs of those with medium diet quality and those who did not drink alcohol (p < 0.05). When the IgG2/1 ratio was examined between alcohol users and nonalcohol, a significant increase was observed about two times in non-alcohol users (p = 0.039). There is a positive significant moderate strength relationship between the second measurements of IgG and anthropometric measurements and the first, second, and avg measurements of IgG with DQI. It was found that there was a negative significant medium-strength relationship between individuals' amount of alcohol consumption and IgG avg (r = -0.535, p = 0.009). CONCLUSIONS: Medium diet quality has been seen to affect antibody levels positively. At the same time, it is thought that alcohol use negatively affects serum IgG antibody response in the long term. Other than that, there was shown to be a correlation between IgG levels and DQI.

16.
Mult Scler Relat Disord ; 91: 105859, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39236649

ABSTRACT

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory disease affecting the central nervous system that may require long-term immunotherapy in relapsing cases. While immunotherapies utilized in neuromyelitis optica spectrum disorder have shown varying efficacy in MOGAD, intravenous immunoglobulin G (IVIG) recently emerged as a promising treatment. Tocilizumab, a monoclonal antibody that targets the interleukin-6 (IL-6) receptor, has been reported to be effective in refractory MOGAD in several case studies, where tocilizumab was introduced primarily due to rituximab failure. METHODS: This retrospective study was conducted in a single center and focused on MOGAD patients receiving tocilizumab therapy, who have shown limited response to various immunotherapies, including intravenous immunoglobulin G (IVIG) maintenance. RESULTS: This study included four patients, three adults, and one child. They experienced a median of 9 attacks (range 6-9) throughout their disease course despite at least two immunotherapies. All patients transitioned to tocilizumab after experiencing a median of two relapses (range 1-3) while on IVIG maintenance for a median of 21.9 months (range 21.3-49.6 months). Following the monthly tocilizumab administration at a dose of 8g/kg, all patients remained relapse-free with a median follow-up duration of 25.0 months (range 9.8-51.3 months) without reported adverse events. CONCLUSION: Targeting the IL-6 pathway appears to offer therapeutic benefits in highly relapsing MOGAD patients who poorly respond to IVIG maintenance therapy.

17.
Article in Russian | MEDLINE | ID: mdl-39269300

ABSTRACT

OBJECTIVE: To study the relationship of the parameters of immunity and systemic inflammation with the structural magnetic resonance imaging (MRI) parameters in patients with mild cognitive impairment (MCI) and pre-MCI undergoing neurocognitive rehabilitation to search for candidate markers of its effectiveness. MATERIAL AND METHODS: The main group included 49 patients, aged ≥60 years, with MCI and pre-MCI with memory impairment, who underwent a course of neurorehabilitation for 5 weeks. The control group included 19 volunteers of similar age with a total MoCA score of ≥25, who did not have cognitive impairment and immuno-inflammatory disorders. The parameters of cellular and humoral immunity and markers of inflammation were studied, and structural MRI was performed. RESULTS: The content of activated natural killer cells (NK-cells) was increased in MCI and pre-MCI (0.63±0.12% vs. 0.22±0.07% in the control group, p=2.2·10-7). The level of immunoglobulin G (IgG) <12.5 g/l in patients with MCI and pre-MCI with the Montreal Cognitive Assessment Scale (MoCA) score <22 was associated with a decrease in the volume of the right nucleus accumbens (376±35 mm3 in patients with IgG <12.5 g/l (p=0.0013) and 480±44 mm3 at IgG <12.5 g/l, 480±44 mm3 in the control group), as well as with a decrease of the thickness and volume of a number of other cortical zones. A logistic regression model including the level of immunoglobulin G, NK cells, CD8+ NK cells and right amygdala volume was constructed to predict the number of MoCA scores 6 months after the course of rehabilitation (R2=0.57; p<1·10-5; standard error of estimate: 2.93). CONCLUSION: As a result of this work, the perspectives of assessing the immunological parameters in combination with socio-demographic data and morphometric changes of the brain as potential prognostic markers of the dynamics of cognitive impairment in patients with MCI and pre-MCI after neurorehabilitation has been shown.


Subject(s)
Biomarkers , Cognitive Dysfunction , Killer Cells, Natural , Magnetic Resonance Imaging , Humans , Cognitive Dysfunction/immunology , Male , Female , Aged , Middle Aged , Killer Cells, Natural/immunology , Immunoglobulin G/blood , Inflammation/immunology
18.
Biomol NMR Assign ; 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39269603

ABSTRACT

Research on camelid-derived single-domain antibodies (sdAbs) has demonstrated their significant utility in diverse biotechnological applications, including therapy and diagnostic. This is largely due to their relative simplicity as monomeric proteins, ranging from 12 to 15 kDa, in contrast to immunoglobulin G (IgG) antibodies, which are glycosylated heterotetramers of 150-160 kDa. Single-domain antibodies exhibit high conformational stability and adopt the typical immunoglobulin domain fold, consisting of a two-layer sandwich of 7-9 antiparallel beta-strands. They contain three loops, known as complementary-determining regions (CDRs), which are assembled on the sdAb surface and are responsible for antigen recognition. The single-domain antibody examined in this study, sdAb-mrh-IgG, was engineered to recognize IgG from rats, mice, but it also weakly recognizes IgG from humans (Pleiner et al. 2018). A search of the Protein Data Bank revealed only one NMR structure of a single-domain antibody, which is unrelated to sdAb-mrh-IgG. The NMR chemical shift assignments of sdAb-mrh-IgG will be utilized to study its molecular dynamics and interactions with antigens in solution, which is fundamental for the rational design of novel single-domain antibodies.

19.
Clin Res Hepatol Gastroenterol ; 48(8): 102442, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39103121

ABSTRACT

BACKGROUND: Autoimmune hepatitis (AIH) patients can present with advanced fibrosis at diagnosis or may progress to the same if biochemical remission on treatment is not achieved. METHODS: We conducted a single-center retrospective analysis of 34 pediatrics and 39 adult AIH patients. Three pathologists, blinded to clinical information, reviewed the diagnostic liver biopsy (DLB) slides of AIH patients. We evaluated the impact of clinical, laboratory, and histopathologic parameters on outcomes including biochemical remission (BR). RESULTS: Incidence of advanced (Ludwig stage 3 or 4) fibrosis on DLB was 45.2 %. AIH patients with advanced fibrosis had higher median Ishak score (p < 0.001) and higher IgG level (p = 0.01) at diagnosis. The incidence of BR at 6-month (31.2% vs. 88.6 %, p = 0.001) and 1-year (68.8% vs. 88.6 %, p = 0.04) post-diagnosis was significantly lower in AIH patients with advanced fibrosis. Although not statistically significant, a higher proportion of AIH patients with advanced fibrosis were on high dose of steroids (58% vs. 37.9 %, p = 0.1) at 1 year post diagnosis. Higher serum IgG level at diagnosis was associated with lower odds of achieving BR at 6-month (p = 0.004) and 1-year (p = 0.03) post-diagnosis in multivariate analysis. Pediatric age at diagnosis (p = 0.02) was associated with higher steroid dose at 1-year post-diagnosis in univariate analysis. CONCLUSIONS: Findings of advanced fibrosis on DLB of AIH patients was accompanied by more pronounced necro-inflammatory activity and higher serum IgG level, which translated to lower rates of BR and higher exposure to steroids during the first year after diagnosis.


Subject(s)
Hepatitis, Autoimmune , Liver Cirrhosis , Remission Induction , Humans , Hepatitis, Autoimmune/blood , Hepatitis, Autoimmune/pathology , Hepatitis, Autoimmune/drug therapy , Hepatitis, Autoimmune/diagnosis , Hepatitis, Autoimmune/complications , Retrospective Studies , Female , Male , Adult , Biopsy , Child , Liver Cirrhosis/pathology , Liver Cirrhosis/blood , Liver Cirrhosis/diagnosis , Adolescent , Middle Aged , Liver/pathology , Young Adult , Child, Preschool , Immunoglobulin G/blood
20.
Lupus ; 33(11): 1212-1219, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39129197

ABSTRACT

BACKGROUND: The exact cause of systemic lupus erythematosus (SLE) is still unknown. However, hormonal, genetic, and environmental factors may play significant roles in its development. Infection has been recognized as a crucial trigger for SLE development. Several studies have reported a higher prevalence of Toxoplasma gondii infections in patients with SLE than in healthy individuals. However, these results were inconsistent. Therefore, this study aimed to conduct a systematic review and meta-analysis of published studies to provide a definitive conclusion regarding the relationship between T. gondii infection and SLE. MATERIALS AND METHODS: We conducted a comprehensive search across diverse databases using an array of search tools to uncover pertinent literature. Following the stringent application of the inclusion and exclusion criteria, we carefully selected the appropriate reports for our meta-analysis. Using Comprehensive Meta-Analysis software v4, we analyzed the data and determined the prevalence of antibodies against T. gondii in patients affected with SLE. To investigate the correlation between T. gondii seropositivity and SLE, we computed the risk ratios (RRs) and 95% confidence intervals (CI). RESULTS: Eleven studies were considered eligible for inclusion in the present study. The prevalence of anti-IgG and IgM antibodies against T. gondii was 33.9% and 7.7%, respectively. A significant association between T. gondii IgG seropositivity and SLE was observed when compared to the controls (risk ratio = 2.14, 95% CI = 1.42 to 3.22, p = .000). However, IgM seropositivity against T. gondii was comparable between patients with SLE and healthy controls. CONCLUSIONS: In summary, this study suggests that T. gondii IgG is more prevalent in patients with SLE than in healthy individuals in areas where T. gondii infections are more frequent. However, an exact cause-and-effect relationship still needs to be established. Therefore, additional research is necessary to validate these findings and to investigate the underlying mechanisms.


Subject(s)
Antibodies, Protozoan , Lupus Erythematosus, Systemic , Toxoplasma , Toxoplasmosis , Humans , Antibodies, Protozoan/blood , Antibodies, Protozoan/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/immunology , Seroepidemiologic Studies , Toxoplasma/immunology , Toxoplasmosis/blood , Toxoplasmosis/complications , Toxoplasmosis/epidemiology , Toxoplasmosis/immunology
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