Fibroinflammatory Disorder Research Articles

Slide laryngotracheopexy for idiopathic subglottic stenosis.

Idiopathic subglottic stenosis (iSGS) is a rare fibroinflammatory disorder characterized by scar tissue formation in the subglottic and tracheal regions. This study evaluated the long-term outcomes of a novel, single-step surgical technique that redefines the glottic and subglottic airway using local tracheal grafts. Thirteen patients (2 male and 11 female) diagnosed with iSGS who underwent slide laryngotracheopexy were enrolled in this study. The diagnosis of iSGS was confirmed through endoscopic assessment, CT scanning, and autoimmune blood testing. Patients completed post-operative Voice Handicap Index (VHI), Quality of Life (QoL), and MD Anderson Dysphagia Inventory (MDADI) questionnaires, and spirometry assessments were conducted. All patients were successfully extubated in the operating room following surgery. None of the patients required intensive care unit treatment. The average hospital stay was 14 days. A temporary tracheotomy was needed in one case because of excessive crusting. Adjuvant endolaryngeal laser surgery was performed in three cases. In one case, mitomycin-C therapy was administered to treat granulation. Post-operative quality of life (QoL) assessment, peak inspiratory flow (PIF), and scores from the MDADI and VHI questionnaires were 9.0 (± 2.2), 2.8l/s (± 0.83), 95.6 (± 4.3), and 18.7 (± 13.4), respectively. Slide laryngotracheopexy was a safe and dependable technique for cases classified as Cotton-Myers II-IV grade iSGS. The use of a tracheal flap was advantageous to ensure optimal mucosal function. Slide laryngotracheopexy may be employed following multiple endolaryngeal interventions, whereas adjuvant CO2 laser surgery or mitomycin-c therapy may be considered in cases involving granulation tissue formation. Retrospective case series review.

Update on Autoimmune Pancreatitis and IgG4-Related Disease.

Autoimmune pancreatitis is an increasingly recognized inflammatory type of subacute pancreatitis; two subtypes of autoimmune pancreatitis have been identified so far: the "lymphoplasmacytic" type 1 variant and the "neutrophilic" type 2 variant. Type 1 autoimmune pancreatitis represents the most common manifestation of IgG4-related disease, a fibro-inflammatory disorder characterized by elevated IgG4 levels in the serum and affected tissues. Type 2 autoimmune pancreatitis is a pancreas-specific disorder that frequently occurs in the context of inflammatory bowel diseases. Due to the complexity of both diseases, a comprehensive work up with imaging, laboratory, and histological studies is required to achieve a diagnosis and rule out malignancies. Glucocorticoids represent the cornerstone of the treatment, often supported by other immunosuppressive drugs in case of steroid intolerance or aggressive disease. Maintenance treatment is often employed in type 1 autoimmune pancreatitis because of the higher relapse rate compared with type 2 autoimmune pancreatitis. In this review, we summarize the key concept of autoimmune pancreatitis, delve into the differential diagnosis between the two subtypes, and cover the recent relevant research findings and pressing unmet needs.

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.

Transcriptomic analysis of pancreatic tissue from humans and mice identifies potential gene signatures and unexplored pathways during progression from acute to chronic pancreatitis.

A comprehensive understanding of the molecular pathogenesis of chronic pancreatitis (CP), a fibroinflammatory disorder of the pancreas, is warranted for the development of targeted therapies. The current study focused on comparing the transcriptomes of pancreatic tissues obtained from patients with CP with those of two rodent models of chemically induced CP to identify dysregulated genes/signaling pathways. Pancreatitis was induced in mice using cerulein and L-arginine. Pncreatic tissues were obtained from humans and mice. The RNA was isolated, and the transcriptomes were generated using the GeneChip Human Transcriptome Array 2.0 and Clariom D Mouse Array respectively. Differentially expressed genes with log2-fold changes ≥ +2 and ≤ -2 were considered for functional and signaling pathway enrichment analysis. The expression of NUCB2, which plays a role in β-cell function, was validated by ELISA in acute pancreatitis (AP) and immune cell responses in AP and CP using flow cytometry. The current study identifies L-arginine-induced CP as a better model for investigating the pathogenesis of human CP, with greater similarity in dysregulated genes (22%), transcription factors (34%) and enriched pathways (58%) compared to cerulein model (2%, 11% and 9%) respectively. Nesfatin-1, encoded by NUCB2, was decreased in patients with AP (12% nondiabetic, 41% post pancreatitis diabetes). The Th1 immune cell response was greater in the patients with AP (44%), whereas Th17 immune response was greater in patients with CP (18%). Our study highlights potential novel and unexplored pathways involved in inflammation, fibrosis, and pain in CP and paves the way for testing them as putative drug targets using a severe disease model.

INVESTIGATION OF GEOSPATIAL DISPARITIES IN CHRONIC PANCREATITIS OUTCOMES.

Chronic pancreatitis (CP) is a fibro-inflammatory disorder characterized by abdominal pain and exocrine and endocrine pancreatic insufficiency resulting in significant morbidity. This study evaluates the impact of geospatial parameters, assessed using the Social Vulnerability Index (SVI), a tool comprising sixteen social attributes, on CP outcomes, including opioid use. We conducted a retrospective analysis of CP patients with available addresses followed at our pancreas center. We reviewed demographics, clinical variables including number of CP flares, local complications, pancreatic function, and healthcare-resource utilization (HRU) including imaging, endoscopic procedures, and surgeries, and outpatient opioid prescriptions measured in morphine milligram equivalents (MME). Regression analysis was performed to assess the association between outcomes and SVI [divided into 4 quartiles (I-IV; IV being most vulnerable]. Among 324 CP patients followed over 8 years, we noted trends of higher dependence on governmental insurance or no insurance among patients in higher SVI quartiles (III/IV vs. I/II) but no differences in demographics, comorbidities, or etiology of CP. In patients residing in more vulnerable SVI quartiles, we noted significantly higher frequency of hospitalizations for CP flares and lower daily MME. Rates of exocrine and endocrine pancreatic dysfunction and HRU were similar across all SVI quartiles. Despite multidisciplinary guideline-based care, residence in the most vulnerable neighborhoods may be associated with less opioid use and more frequent CP flares, suggesting possible inadequate pain control in these patients. These findings should guide prospective investigation of the impact of geospatial social determinants of health in CP and efforts to mitigate the above disparities.

Seven Cases of Immunoglobulin G4-Related Disease in Submandibular Glands

Immunoglobulin G4-related disease (IgG4-RD) is a chronic fibroinflammatory systemic disorder. Predominantly, patients with submandibular swelling are diagnosed with this disease in otorhinolaryngology. However, due to its rarity and the limited understanding of the disease, accurate diagnosis can be challenging. Through a retrospective review of seven cases of IgG4- RD patients, our study analyzed the symptoms, diagnostic approaches, treatment modalities, and prognosis of the condition, contributing to a better understanding of IgG4-RD.

Correlations between IgG4-related disease and allergic reactions: implications for future therapeutic strategies.

IgG4-related disease (IgG4-RD) is a chronic multi-organ immune fibroinflammatory disorder. It can affect almost any organ, with the primary treatment being corticosteroids, sometimes supplemented with conventional immunosuppressants or biological agents, such as rituximab therapy. The occurrence of this disease is associated with aberrant adaptive immune responses, but its specific pathological mechanisms remain unclear. Patients with IgG4-RD often have allergic diseases such as asthma, rhinitis, and urticaria.Allergic reactions and IgG4-RD may share similar pathological mechanisms, including activation of Th2 immune responses, excessive secretion of IgG4 and IgE, and increased blood/tissue eosinophils. The aim of this article is to review the allergy-like characteristics of IgG4-RD and emphasise the potential of allergy-targeted therapies in the treatment of IgG4-RD patients.

New Insights into Chronic Pancreatitis: Potential Mechanisms Related to Probiotics.

Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut-pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), the facilitation of short-chain fatty acids' (SCFAs) production, and the activation of glucagon-like peptide-1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we discuss research in other disease models that have used probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut-pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.

IgG4-related disease with subcutaneous involvement and the associated diagnostic challenges with MRI.

IgG4-related disease is a rare fibroinflammatory disorder characterized by the infiltration of IgG4-rich plasma cells. Herein, we report a case of IgG4-related disease of the subcutaneous tissue with atypical MRI findings and difficulties in the histopathological examination using needle biopsy. Based on the clinical presentation and MRI findings, the patient was diagnosed with a benign myxoid or cystic tumor. Additionally, histopathological findings from a needle biopsy suggested a myxoma. Therefore, the correct diagnosis of IgG4-related disease was not made preoperatively. The resected specimens confirmed IgG4-related disease with an IgG4/IgG ratio > 80%. Previous reports have shown that the MRI findings of IgG4-related disease mimic both malignancy and inflammation; surprisingly, the features of subcutaneous IgG-related disease, including tail sign, unclear border, and heterogeneous enhancement, were similar to those found in sarcoma. Therefore, histopathological findings are needed for a correct diagnosis. Furthermore, careful examination is essential because the neoplasm and inflammation may overlap with IgG4-related disease, and needle biopsy is not fully reflective of the tumor. As is highlighted in the present case, IgG4-related disease is often misdiagnosed; therefore, clinicians should adequately recognize that even if the histopathological findings in biopsy were consistent with those observed in the MRI, misdiagnosis may occur.

A case of type 2 diabetes mellitus complicated with IgG4-related retroperitoneal fibrosis and a literature review.

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can affect multiple organs throughout the body, predominantly in middle-aged and elderly males, with a male-to-female ratio of 2꞉1 to 3꞉1. IgG4-related retroperitoneal fibrosis (IgG4-RPF), a rare subtype of IgG4-RD, has an unclear etiology, and its comorbidity with type 2 diabetes mellitus is also uncommon. A lack of awareness of this condition in clinical practice can easily lead to misdiagnosis. On July 14, 2016, the Third Xiangya Hospital of Central South University admitted a patient with type 2 diabetes mellitus complicated by IgG4-RPF. Following comprehensive treatment, including blood glucose and blood pressure control, kidney protection, circulation improvement, and the use of prednisone, the patient's condition significantly improved. The retroperitoneal fibrotic mass decreased in size, renal function improved, and serum IgG4 levels decreased. After 8 years of follow-up, the condition did not recur. Analyzing this case in conjunction with a literature review suggests that the development of IgG4-RPF in diabetic patients may be related to chronic inflammation from metabolic syndrome and atherosclerotic plaques associated with long-standing diabetes. This provides valuable clinical ideas for clinicians in diagnosing and treating this rare comorbidity.

IgG4-related Renal Disease Case Report and Review of Literature

ABSTRACT IgG4-related disease (IgG4-RD) is a clinical entity that involves multiple organs and is characterized by high levels of serum IgG4. We present a case of an elderly male reporting fatigue and weight loss, who after extensive workup, was diagnosed as a case of IgG4-related renal disease on kidney biopsy. Clinical Profile: A 73-year-old male patient, a reformed smoker with a history of acute coronary syndrome and bronchial asthma, presented with fatigue and weight loss for 6 months. Clinical examination was unremarkable. Investigations revealed mild anemia, azotemia, hyperglobulinemia, bland urinary sediment, insignificant proteinuria, and symmetrically enlarged kidneys. A kidney biopsy was performed, which demonstrated features of IgG4-related tubulointerstitial nephritis (TIN). Simultaneous serological investigations revealed a Kappa/Lambda ratio of 2.12, IgG–3110 mg/dL, and IgG4–3.56 g/L. The patient was treated with oral prednisolone for 6 months. Discussion: IgG4-related disease is a multisystem immune fibro-inflammatory disorder of the elderly with a male preponderance, which involves all organs except the synovium. IgG4-related TIN presents with an insidious rise of creatinine, elevated IgG4 levels, peripheral eosinophilia in 40% of individuals, anti-nuclear antibodies (ANA) positive status in many, and hypocomplementemia. It is characterized by lymphoplasmacytic infiltration with IgG4+ plasma cells with IgG4/IgG ratio >40%, eosinophilic infiltrate, storiform fibrosis, and immune complexes in the tubular basement membrane. The mainstay of treatment is oral corticosteroids, with relapse noted in the majority, followed by a chronic indolent course. Conclusion: IgG4-related diseases are an emerging entity and have only been recently recognized. Awareness of the disease and a high index of suspicion is essential for early diagnosis to avoid irreversible organ damage.

Dermatological Manifestations of IgG4-Related Disease: Insights into the Immunopathogenesis and Clinical Spectrum

This review aims to provide insights into the immunopathogenesis and clinical spectrum of dermatological manifestations in IgG4-related disease (IgG4-RD), a systemic fibroinflammatory disorder characterized by tissue infiltration of IgG4-positive plasma cells. Through comprehensive immunohistochemical analyses of skin biopsies from patients with IgG4-RD-associated cutaneous lesions, researchers endeavor to understand the role of IgG4- mediated immune responses, cytokine signaling, and fibrotic pathways in driving skin inflammation and fibrosis. Moreover, this research seeks to characterize the clinical presentation and treatment response of IgG4-RD-related dermatological manifestations to immunomodulatory therapies. Understanding the complex immunopathogenic mechanisms underlying IgG4-RD-related skin lesions may contribute to the refinement of diagnostic criteria and therapeutic strategies for managing this emerging autoimmune condition. Future research directions could include exploring novel biomarkers, identifying potential therapeutic targets, and investigating the long-term outcomes of dermatological involvement in IgG4-RD.

A case of diabetic mastopathy: An unusual breast lesion mimicking cancer in type 1 diabetes mellitus

Diabetic mastopathy is a rare fibroinflammatory disorder seen among middle aged and premenopausal age group. It is also called lymphocytic mastopathy or sclerosing lymphocytic mastitis. This is seen associated with type 1 diabetes mellitus and other autoimmune disorders specially related to endocrine disorders like thyroid. The definite diagnosis of diabetic mastopathy is truly based on biopsy and histopathological examination.A 33 year old female came to hospital with complaints of swelling in right breast since one month and pain since one week. She was a known case of type 1 diabetes mellitus since 10 years and on regular medications. Radiological Impression was possibilities of mastitis with abscess formation more likely to be considered. But infiltrating malignant neoplasm with areas of necrosis is also a differential diagnosis. Our histopathology laboratory, we received incision biopsy from right breast and microscopic examination from multiple tissue sections showed breast parenchyma with extensive fibrosis and periductal inflammatory infiltrate predominantly lymphocytes, plasma cells and a few neutrophils. Some of the ducts show epithelial proliferation forming bridges and micropapillae. Histopathological diagnosis was Lymphocytic Mastitis with features of Atypical Ductal Hyperplasia.: The diagnosis of Diabetic Mastopathy is based on clinical details, radiological evaluation and biopsy correlation. Sometimes it’s difficult to differentiate from carcinoma breast, so histopathological examination is indicated for a definitive diagnosis and management.

Rapid progression of a coronary artery aneurysm caused by IgG4-related disease

BackgroundIgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder that can affect almost any organ. IgG4-RD has also been reported in coronary arteries as periarteritis. IgG4-related coronary periarteritis may cause coronary artery aneurysms, and IgG4-related coronary artery aneurysms (IGCAs) are life-threatening. We describe a case of a patient with IGCA that highlights the usefulness and limitations of various IGCA evaluation modalities and provides insight into disease pathophysiology. Case summaryA 60-year-old man with IgG4-RD diagnosed 2 years before and with IGCA at the proximal right coronary artery (RCA) on coronary angiography (CAG) 9 months prior to admission to the hospital presented with acute coronary syndrome. Emergent CAG revealed the rapid progression of IGCA at the RCA, an obstruction of the diagonal branch, and stenosis of the left anterior descending artery (LAD) and the high lateral branch (HL). The patient underwent percutaneous coronary intervention for the diagonal branch. The RCA aneurysm was resected and bypassed with a saphenous vein graft (SVG); coronary bypass grafting (left internal mammary artery to LAD and SVG to HL) was performed. Pathological findings showed inflammatory cell infiltration and disruption of the elastic plate. ConclusionIGCAs require careful follow-up with computed tomography scans for early detection of aneurysmal enlargement.

IgG4-Related disease with diffuse myopericardial involvement- value of CMR: a case report and literature review of cardiac involvement

BackgroundIgG4-related disease is a fibro-inflammatory disorder with an unknown etiology, which can affect multiple organ systems, including the cardiovascular system. While most reported cases of cardiovascular involvement are primarily associated with the aorta, there have been sporadic reports of isolated cardiac involvement.Case presentationThis paper presents a documented case of IgG4-related systemic disease with symptoms indicative of restrictive cardiomyopathy. Subsequent Cardiac Magnetic Resonance imaging revealed diffuse myopericardial involvement, characterized by pericardial thickening and enhancement, accompanied by subepicardial and myocardial infiltration. Considering the rarity of cardiac involvement in our case, we conducted a thorough review of the existing literature pertaining to various patterns of cardiac involvement in IgG4-related disease, as well as the diagnostic modalities that can be employed for accurate identification and assessment.ConclusionsThis case report sheds light on the importance of recognizing and evaluating cardiac manifestations in IgG4-related systemic disease to facilitate timely diagnosis and appropriate management.

Multimodality Imaging Features of Immunoglobulin G4-related Vessel Involvement.

Immunoglobulin 4 (IgG4)-related disease is a chronic immune-mediated fibroinflammatory disorder. Involvement of the vascular system, including large- and medium-sized vessels, is increasingly recognized. The varied appearances of vascular involvement reflect the sequela of chronic inflammation and fibrosis and can include aortitis and periaortitis with resultant complications such as aneurysm formation and dissection. A diagnosis of IgG4-related large vessel involvement should be considered when there is known or suspected IgG4-related disease elsewhere. Other organs that are typically affected in IgG4-related disease include the lacrimal and salivary glands, thyroid, pancreas, biliary tree, lungs, kidneys, and meninges. Diagnosis typically requires careful correlation with clinical, imaging, serum, and pathologic findings. Patients may be managed with corticosteroid therapy or the anti-CD20 monoclonal antibody, rituximab, if needed. The varied clinical presentations and imaging features of large vessel involvement are discussed herein. Keywords: Vascular, Inflammation, Aorta, IgG4-related Vessel Involvement © RSNA, 2024.

Unveiling the molecular Hallmarks of Peyronie's disease: a comprehensive narrative review.

Peyronie's disease, a fibroinflammatory disorder, detrimentally impacts the sexual well-being of men and their partners. The manifestation of fibrotic plaques within penile tissue, attributed to dysregulated fibrogenesis, is pathognomonic for this condition. The onset of fibrosis hinges on the perturbation of the equilibrium between matrix metalloproteinases (MMPs), crucial enzymes governing the extracellular matrix, and tissue inhibitors of MMPs (TIMPs). In the context of Peyronie's disease, there is an elevation in TIMP levels coupled with a decline in MMP levels, culminating in fibrogenesis. Despite the scant molecular insights into fibrotic pathologies, particularly in the context of Peyronie's disease, a comprehensive literature search spanning 1995 to 2023, utilizing PubMed Library, was conducted to elucidate these mechanisms. The findings underscore the involvement of growth factors such as FGF and PDGF, and cytokines like IL-1 and IL-6, alongside PAI-1, PTX-3, HIF, and IgG4 in the fibrotic cascade. Given the tissue-specific modulation of fibrosis, comprehending the molecular underpinnings of penile fibrosis becomes imperative for the innovation of novel and efficacious therapies targeting Peyronie's disease. This review stands as a valuable resource for researchers and clinicians engaged in investigating the molecular basis of fibrotic diseases, offering guidance for advancements in understanding Peyronie's disease.

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis: A Multicenter, Cross-Sectional Study.

Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations. NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear cells (PBMCs) from controls (n = 16), AP/RAP (n = 17), and CP (n = 15) were measured by cytometry by time-of-flight. Plasma NGAL was elevated in subjects with CP compared with controls (area under the curve [AUC] = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, body mass index, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared with CP without diabetes ( P < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower, whereas dihomo-γ-linolenic and adrenic acids were elevated in CP ( P < 0.05). Linoleic acid was elevated in CP with diabetes compared with CP subjects without diabetes ( P = 0.0471). Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.

Galectin-3 and prohibitin 1 are autoantigens in IgG4-related cholangitis without clear-cut protective effects against toxic bile acids.

IgG4-related cholangitis (IRC) is the hepatobiliary manifestation of IgG4-related disease, a systemic B cell-driven fibro-inflammatory disorder. Four autoantigens have recently been described in IgG4-RD: annexin A11, galectin-3, laminin 511-E8, and prohibitin 1. We have previously reported a protective role of annexin A11 and laminin 511-E8 in human cholangiocytes against toxic bile acids. Here, we explored the potentially protective role of the carbohydrate-binding lectin galectin-3 and the scaffold proteins prohibitins 1 and 2. Anti-galectin-3, anti-prohibitin 1 and 2 autoantibody positivity in IRC and healthy and disease (primary sclerosing cholangitis (PSC)) control sera was assessed by ELISA/liquid chromatography-tandem mass spectrometry (LC-MS/MS). Human H69 cholangiocytes were subjected to short hairpin RNA (shRNA) knockdown targeting galectin-3 (LGALS3), prohibitin 1 (PHB1), and prohibitin 2 (PHB2). H69 cholangiocytes were also exposed to recombinant galectin-3, the inhibitor GB1107, recombinant prohibitin 1, and the pan-prohibitin inhibitor rocaglamide. Protection against bile acid toxicity was assessed by intracellular pH (pHi) measurements using BCECF-AM, 22,23-3H-glycochenodeoxycholic acid (3H-GCDC) influx, and GCDC-induced apoptosis using Caspase-3/7 assays. Anti-galectin-3 autoantibodies were detected in 13.5% of individuals with IRC but not in PSC. Knockdown of LGALS3 and galectin-3 inhibition with GB1107 did not affect pHi, whereas recombinant galectin-3 incubation lowered pHi. LGALS3 knockdown increased GCDC-influx but not GCDC-induced apoptosis. GB1107 reduced GCDC-influx and GCDC-induced apoptosis. Recombinant galectin-3 tended to decrease GCDC-influx and GCDC-induced apoptosis. Anti-prohibitin 1 autoantibodies were detected in 61.5% and 35.7% of individuals with IRC and PSC, respectively. Knockdown of PHB1, combined PHB1/2 KD, treatment with rocaglamide, and recombinant prohibitin 1 all lowered pHi. Knockdown of PHB1, PHB2, or combined PHB1/2 did not alter GCDC-influx, yet knockdown of PHB1 increased GCDC-induced apoptosis. Conversely, rocaglamide reduced GCDC-influx but did not attenuate GCDC-induced apoptosis. Recombinant prohibitin 1 did not affect GCDC-influx or GCDC-induced apoptosis. Finally, anti-galectin-3 and anti-prohibitin 1 autoantibody pretreatment did not lead to increased GCDC-influx. A subset of individuals with IRC have autoantibodies against galectin-3 and prohibitin 1. Gene-specific knockdown, pharmacological inhibition, and recombinant protein substitution did not clearly disclose a protective role of these autoantigens in human cholangiocytes against toxic bile acids. The involvement of these autoantibodies in processes surpassing epithelial secretion remains to be elucidated.

Coexistence of Colorectal Cancer and Immunoglobulin G4-Related Disease in the Same Lesion: A Rare Case with Molecular Classification.

Immunoglobulin G4-related disease (IgG4-RD) is a novel fibroinflammatory disorder characterized by enlargement of the involved organs, elevated IgG4 levels, and abundant infiltration of IgG4-positive plasma cells. Indeed, primary colon cancers arising from IgG4-RD are rare. This case report describes a rare occurrence of simultaneous colorectal cancer and IgG4-RD in the same lesion in a 62-year-old male patient. The patient underwent a right hemicolectomy under the suspicion of primary colon cancer. The mass was grossly well-defined and yellowish tan, and the background colon was fibrotic. Microscopically, the tumor cells showed glandular differentiation characteristic of adenocarcinoma in a background of dense lymphoplasmacytic infiltration with fibrosis and obliterative phlebitis in the pericolic fat tissue. IgG4 immunohistochemical staining showed diffuse positivity in infiltrating plasma cells. The patient was administered adjuvant chemotherapy and prednisolone therapy. The patient's serum IgG4 levels gradually decreased, and a follow-up positron emission tomography-computed tomography scan 1 year after surgery showed no evidence of local or distant recurrence of colorectal cancer. IgG4-RD occurring concurrently with primary colon adenocarcinoma has not been reported. Increased awareness of this rare coexistence can guide clinicians in navigating diagnostic complexities and selecting optimal therapeutic strategies.