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A woman in her 20s presented with 6 weeks of fever, persistent vomiting and 28% loss of body weight. Symptoms were refractory to treatment with antiemetics and broad spectrum antibiotics.Further investigation via oesophageogastroduedenoscopy revealed a large gastric ulcer and pyloric stricture, causing gastric outlet obstruction (GOO). Biopsies of the stomach and duodenum showed plasma cell infiltration with a large proportion being IgG4 positive.Treatment with methylprednisolone, and later prednisolone, quickly improved inflammatory markers and symptoms. Balloon dilatation of the pyloric stricture also improved vomiting, allowing eventual re-establishment of oral nutrition. The patient made a full recovery with maintenance treatment on mycophenolate mofetil.IgG4-related disease (IgG4-RD) is a multisystem disorder with unpredictable presentation. The case highlights diagnostic challenges in IgG4-RD and identifies it as a rare differential in upper gastrointestinal symptoms. To our knowledge this is the first published case of IgG4-RD in the duodenum causing GOO., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: No conflict of interest was declared by the authors.

Competing Interests: The authors declare no conflict of interest.

IgG4-related disease (IgG4-RD) is a complex multi-system inflammatory disorder that can affect various organs in the body. This condition is characterized by elevated levels of immunoglobulin G subclass 4 (IgG4) and the presence of specific histopathological features. While neurological involvement is not as common as in other organs, when it occurs, it can lead to hypertrophic pachymeningitis and hypophysitis. Here, we present a case of a 53-year-old male with right-sided hemicranial headache and diplopia. Computed tomography revealed a soft tissue density lesion in the middle ear cavity and mastoid antrum with the destruction of the mastoid septae. Magnetic resonance imaging revealed a lesion in the right middle ear cavity associated with pachymeningitis and right sigmoid and transverse sinus thrombosis. Tissue pathology revealed dense plasma cell-rich chronic inflammation with storiform fibrosis. Immunohistochemistry was positive for IgG4. Hence, a diagnosis of IgG4-related disease causing mastoiditis, pachymeningitis and cerebral venous thrombosis was made. The patient was successfully operated and treated with steroids. IgG4-RD remains a rare but serious condition. It is crucial to identify and treat this condition promptly as it can lead to permanent organ damage. When patients continue to experience middle ear symptoms after an infection has been treated and cancer has been ruled out, it is important to consider inflammatory conditions as a differential diagnosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Khaladkar et al.)

Context.—: Manifestations of immunoglobulin G4-related disease (IgG4-RD) occur in several organ systems and anatomic locations, including the nasal cavity and paranasal sinuses. Other processes affecting the sinonasal tract, such as chronic rhinosinusitis, aspirin-exacerbated respiratory disease, and nasal polyposis, also involve IgG4., Objective.—: To characterize an association between IgG4 and nasal lesions arising in the clinical context of intranasal drug use., Design.—: The cases of 3 patients (2 with histories of intranasal cocaine abuse, and 1 with intranasal heroin abuse) were evaluated. Clinical features of each case were compiled from the electronic medical record. Histologic morphology of surgical specimens was examined. Immunohistochemical staining was performed to assess involvement of/association with IgG4., Results.—: Clinical features of these lesions included diffuse necrotic fibrinous debris, scarring, and endoscopically evident inflammation. Tissue sections showed acutely and chronically inflamed respiratory-type mucosa with abundant IgG4-positive plasma cells. Although these cases share some aspects in common with IgG4-RD, other definitive characteristics are absent, and notable differences exist., Conclusions.—: This series provides the first demonstration of increased IgG4 expression in nasal lesions associated with intranasal drug use. Despite some similarities, the pathologic processes and IgG4-rich infiltrates in these 3 cases seem to represent a different phenomenon that is not IgG4-RD. Although these lesions contain abundant IgG4-positive cells, they should not be mistaken for or conflated with IgG4-RD., (© 2024 College of American Pathologists.)

IgG4-RD is a multisystem fibroinflammatory disease characterized by the infiltration of tissues by IgG4 plasma cells. Combined skin and biliary tract involvement in IgG4-RD has not been described. We present perhaps the most comprehensive analysis of lymphocyte subsets in the first case of IgG4-related generalized skin rash and first case of combined skin and biliary tract manifestations. A 55-year-old male presented with painful jaundice and generalized macular pigmented pruritic eruptions, and CT abdomen revealed biliary obstruction. Ampulla and skin biopsies were subjected to histology and immunostaining. Naïve, central memory (T CM ), effector memory (T EM ), terminally differentiated effector memory (T EMRA ) subsets of CD4+ and CD8+ T cells, T follicular helper subsets, naïve, transitional, marginal zone (MZ), germinal center (GC), IgM memory, and class-switched memory (CSM) B cells, and T follicular regulatory, regulatory B cells, CD4 Treg, and CD8 Treg were analyzed. Serum IgG4 was elevated at 448 mg/dL. Ampula biopsy showed lamina propria fibrosis and increased IgG4-positive plasma cells. Skin punch biopsy showed lymphoplasmacytic infiltrates with a 67% ratio of IgG4+:IgG+ plasma cells. CD4+T N and CD4+T CM decreased, whereas CD4+T EM increased. Naïve B cells increased; transitional, MZ, CSM, GC B cells, and plasmablasts decreased compared to control. CD4 Treg increased, whereas CD8 Treg and Breg decreased. In conclusion, IgG-RD may present with combined biliary tract and generalized dermatological manifestations. Changes in regulatory lymphocytes suggest their role in the pathogenesis of IgG4-RD.

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a systemic inflammatory disease characterised by elevated serum IgG4, IgG4+ cell infiltration, storiform fibrosis, and obliterative phlebitis. While IgG4-RD can affect various organs, gastrointestinal tract involvement is less common. Here, we report a 70-year-old female with IgG4-RD complicated with diffuse and chronic gastrointestinal inflammation, which led to small intestinal perforation. She had been suffering from anorexia, abdominal pain, vomiting, and diarrhoea and hospitalised due to recurrent ileus. Consequently, she was referred due to small intestinal perforation required for surgical intervention. Pathology revealed acute and chronic inflammation with massive IgG4+ plasmacyte infiltration into mucosa of the small intestine and ischaemic change secondarily caused by chronic inflammation. Random biopsies from the mucosa of stomach, duodenum, ileum, and colon also revealed diffuse and massive IgG4+ plasmacyte infiltration in stomach, duodenum, small intestine, and colon. She was diagnosed with IgG4-RD based on the pathological findings and elevated serum IgG4 levels. Glucocorticoid rapidly ameliorated the symptoms. IgG4-RD may cause gastrointestinal manifestations, and histopathological assessment should be considered, even in the absence of specific characteristics of IgG4-RD., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Mass-forming phenotypes of IgG4-related disease (IgG4-RD) mimic malignancy and histological confirmation can be challenging. A woman in her 70s with HIV infection presented with painless obstructive jaundice and weight loss. Magnetic resonance imaging was suggestive of unresectable cholangiocarcinoma. Tumour markers and serum IgG4 were normal. Percutaneous liver biopsy was consistent with IgG4-RD inflammatory pseudotumour, with complete response to glucocorticoid therapy. Two years later, a new episode of obstructive jaundice occurred, with CT showing a solid lesion in the head of the pancreas with double duct sign and encasement of the portal vein. Re-induction therapy was tried without response. Fine-needle biopsy was consistent with pancreatic cancer. Supportive care was offered and the patient died 8 months later, with no signs of disease progression on subsequent imaging. We discuss the challenges of IgG4-RD diagnosis and treatment and the differential diagnosis between mass-forming phenotypes and malignancy, highlighting the difficulties in managing such patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: WZ reports grants from the Chinese National Key Technology Research and Development Program (2022YFC2703103), and National High Level Hospital Clinical Research Funding (2022-PUMCH-C-006). JZ declares no competing interests.

A woman in her 30s presented with a 12-month history of reduced mouth opening and swelling on the right side of her mandible. The swelling was non-tender and firm on palpation. The swelling began to increase in size after the extraction of her carious wisdom tooth. Histopathological and serological examinations confirmed the diagnosis of IgG4-related disease, manifested as a mass in the mandible. The patient was prescribed oral corticosteroids at a tapering dosage over 8 weeks. After 3 months, there was an improvement in the patient's mouth opening and a reduction in the size of the swelling. The patient remains in follow-up care. Including IgG4-related disease in the list of potential diagnoses for oral soft tissue masses is crucial, given their positive response to medical treatment, highlighting the significance of an accurate diagnosis to prevent unnecessary surgery, with oral lesions potentially serving as early indicators before multiorgan complications arise., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

ObjectiveWe aimed to identify serologic parameters that correlate with the disease activity of IgG4-related disease (IgG4-RD) in patients with normal and elevated serum IgG4 concentrations, respectively.MethodsThis retrospective cohort study included 148 patients with IgG4-RD. Patients were categorized into normal (≤201 mg/dL) and elevated (>201 mg/dL) serum IgG4 concentration groups. Disease activity was assessed using the IgG4-RD responder index (RI). The correlations between IgG4-RD RI and serologic parameters (erythrocyte sedimentation rate [ESR], C-reactive protein, C3, C4, IgG4 concentration, IgG concentration, and IgG4/IgG ratio) were evaluated in each group, using Spearman’s correlation coefficient.ResultsOf the 148 patients with IgG4-RD, 38 (25.7%) and 110 (74.3%) patients were categorized into the normal and elevated serum IgG4 concentration groups, respectively. In the normal serum IgG4 concentration group, IgG concentration was the only serologic parameter that showed a significant correlation with IgG4-RD RI (rho=0.411, p=0.013). However, in the elevated serum IgG4 concentration group, ESR (rho=0.196, p=0.041), C3 (rho=-0.432, p

• Imaging features of IgG4-RD in spinal cord: Mimics tumors, challenging diagnosis. • Successful therapy with glucocorticoid and cyclophosphamide interventions. • Thorough evaluation is crucial for optimizing patient outcomes in IgG4-RD. [ABSTRACT FROM AUTHOR]

Abstract IgG4-related disease (IgG4-RD) was recently described in Japan. It is characterised by extensive organ involvement with tissue fibrosis. We assessed the performance of the 2019 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria and the 2020 revised comprehensive diagnostic (RCD) criteria as well as differences between patients with and without IgG4-RD. In this retrospective, single-centre study of 50 patients admitted with suspected IgG4-RD, we evaluated the sensitivity and specificity of both criteria. We also compared clinical characteristics and laboratory data of patients with IgG4-RD (n = 42) and patients without IgG4-RD (n = 8). The ACR/EULAR classification criteria had 88.1% sensitivity and 87.5% specificity for IgG4-RD diagnosis. The RCD criteria had 100% sensitivity and 50% specificity. Patients with IgG4-RD had significantly more affected organs (p = 0.002). Patients with a single affected organ and IgG4-RD had significantly higher serum IgG4/IgG ratios (p = 0.027), lower serum C-reactive protein levels (p = 0.020), and lower total haemolytic complement activity (p = 0.044) than those without IgG4-RD. The ACR/EULAR classification criteria have high specificity and the RCD criteria have high sensitivity for diagnosing IgG4-RD. The number of affected organs is important for diagnosing IgG4-RD.

Abstract: A 50-year-old woman presented a dry syndrome, joint pain, inflammatory syndrome, polyclonal hypergammaglobulinemia, and tubulointerstitial nephritis. Imaging studies (including FDG PET/CT) revealed infrarenal retroperitoneal fibrosis with periaortitis and hypermetabolic osteosclerotic lesions. Bone scintigraphy demonstrated intense uptake in the femoral, tibial, and radial regions, suggestive of non-Langerhans histiocytosis, specifically Erdheim-Chester disease. A bone biopsy confirmed the presence of IgG4-positive plasma cells but no histiocytes. The patient received corticosteroid therapy followed by rituximab, resulting in a complete response. This case suggests an atypical manifestation of bone lesions in IgG4-related disease, emphasizing the diagnostic challenge between IgG4-related disease and Erdheim-Chester disease., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Follicular lymphoma is clinically classified as a common type of indolent non-Hodgkin's lymphoma, and its clinical diagnosis is difficult because B symptoms and elevated soluble interleukin-2 receptor (sIL-2R) levels are less frequent in follicular lymphoma than in other lymphomas. We report a case of follicular lymphoma masquerading immunoglobulin G4-related disease (IgG4-RD) with elevated IgG4 levels. A 67-year-old man presented to our hospital with a 1-year history of deep right supraclavicular and para-aortic lymph node lymphadenopathy on plain computed tomography (CT) findings along with elevated IgG4 levels, and the 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan showed heterogeneous diffuse FDG uptake in the liver, and FDG uptake was noted at multiple sites in the enlarged right supraclavicular and para-aortic lymph nodes. Excisional biopsy of the right supraclavicular lymph node, performed under general anesthesia, showed a tumor-like structure mimicking a normal germinal center in the lymphoid follicle; immunostaining was positive for B-cell lymphoma 2 and CD10 proteins with some plasma cells stained with IgG, only 30% of them were positive for IgG4, and no marked fibrosis characteristic of IgG4-RD was observed; therefore, follicular lymphoma was diagnosed, and all symptoms, including FDG uptake, improved with rituximab monotherapy. Differential diagnoses of slowly progressive generalized lymphadenopathy over the years with elevated serum IgG4 levels include IgG4-RD, Castleman's disease, and indolent lymphoma. Multiple accumulation in the liver on FDG-PET/CT, if found, may suggest indolent lymphoma among them.

Immunoglobulin G4+ (IgG4+)-related disease may lead to lesions in various systemic organs. Based on several cases of patients with suspected IgG4-related Mikulicz's disease, the definitive diagnosis of IgG4-related Mikulicz's disease has been established, depending on head and neck lesions (e.g., swelling of the salivary glands, enlargement of the lacrimal glands, and bilateral paranasal sinus shadow mainly of the maxillary sinus). In this study, we report a case with suspected IgG4-related disease based on findings of abnormal auditory ossicles obtained accidently by temporal bone computed tomography (CT). The patient was a 27-year-old woman. She was previously diagnosed with IgG4-related dacryoadenitis and rhinosinusitis, which did not lead to a definitive diagnosis. Her temporal bone CT during her visit to our hospital due to left aural fullness during the course showed a soft tissue density shadow around the left auditory ossicles. Thereafter, the presence of the shadow led to slow progression of decalcification, mainly of the left incus. The relationship between the symptoms and decalcification of the auditory ossicles during the course was unclear. Although steroid therapy was performed because of rapidly progressive, severe sensorineural hearing loss, her hearing did not recover. No central nervous system lesions were apparent in magnetic resonance imaging. The biopsy of the left auditory ossicles, obtained after her informed consent, showed jelly-like osteolytic changes in the left incus, and microscopic results showed infiltration of IgG4+ plasma cells in the tissue of the auditory ossicles. The direct relationship between her severe sensorineural hearing loss and the pathological findings of the auditory ossicles is unclear. However, to our knowledge, this is the first case report of suspected IgG4-related disease that had pathological changes, mainly of the auditory ossicles.

Abstract Background With widespread clinical application of imaging techniques, renal space-occupying lesions have been identified at an increasing frequency. Here, we report two rare cases, Castleman disease (CD) and IgG4-related disease (IgG4-RD), presenting primarily with the symptoms and imaging findings of kidney malignancy. Case presentation In case 1, an occupying lesion located in the right renal pelvis was detected using magnetic resonance imaging in a 32-year-old female who presented with hematuria and lumbago. First misdiagnosed as carcinoma of the renal pelvis, the patient underwent right radical nephroureterectomy. However, postoperative pathological and immunohistochemistry studies finally confirmed the diagnosis of CD. In case 2, a 45-year-old male presented with the chief complaint of anuria. Nephrostomy and renal biopsy indicated lymphoma, following which, antegrade urography and computed tomography urography were performed, which revealed bilateral hydronephrosis and mass lesions around the renal pelvis. Partial resection of the masses and frozen section examination indicated the diagnosis of CD. However, the results of postoperative histopathology and immunohistochemistry combined with serum IgG4 were consistent with IgG4-RD. Both the patients recovered well after drug treatment without recurrence of the diseases. Conclusions Inflammatory pseudotumor of CD and IgG4-RD with kidney involvement are primarily diagnosed by postoperative histopathology and can pose a preoperative diagnostic challenge because these lesions can masquerade as kidney malignancy. Therefore, we recommend core biopsy as a nonnegligible procedure to evaluate renal masses and potentially prevent unnecessary surgical treatment.

Abstract Background Paratesticular fibrous pseudotumour is a rare benign growth with unclear pathogenesis and clinical management. It has been linked to Serum IgG4-related disease. This mass can notoriously masquerade around as a malignancy; however, a conservative (testis sparing) approach is sufficient as surgical management. Case presentation We present the case of a 35-year-old gentleman who presented with a slow growing paratesticular mass, raising the suspicion of a malignancy. However, normal tumour markers and benign appearance on imaging modalities compelled us to give trial of local excision with intra-operative frozen section analysis. After confirmation of benign pathology of the mass, the incision was closed. Final histopathology confirmed the diagnosis of benign paratesticular fibrous pseudotumour, and serum IgG levels were noted to be elevated. Conclusion Thus, using tumour markers, radiological imaging and intraoperative frozen section, a potential radical resection can be avoided, testis sparing surgery, employed.

Abstract Background It is difficult to distinguish between multicentric Castleman’s disease (MCD) and IgG4-related lung disease (IgG4-LD), an IgG4-related disease (IgG4-RD) in the lung. Methods We focused on IL-6, which is elevated in MCD, to distinguish between MCD and IgG4-LD by RNAscope, a highly sensitive RNA in situ method. Six cases of MCD and four cases of IgG4-LD were selected. Results In all cases of MCD and IgG4-LD, 10 or more IgG4-positive cells were found in one high-power field. All MCD cases were inconsistent with the pathological IgG4-related comprehensive diagnostic criteria, but 2 of 6 cases had an IgG4/IgG ratio greater than 40%. In all IgG4-LD cases, histological features were consistent with the pathological IgG4-RD comprehensive diagnostic criteria. IL-6 expression was observed in all MCD and IgG4-LD cases except for one IgG4-LD biopsy. IL-6-expressing cells were mainly identified in the stroma. Sites of IL-6 expression were not characteristic and were sparse. IL-6 expression tended to be higher in MCD compared with IgG4-LD. A positive correlation was found between the IL-6 H-score and serum IL-6 level. Conclusion Differences in IL-6 expression may help distinguish between MCD and IgG4-LD. In addition, the presence of high IL-6 levels may help elucidate the pathological mechanisms of IgG4-LD.

Abstract IgG4‐related disease (IgG4‐RD) is a fibroinflammatory disorder signified by aberrant infiltration of IgG4‐restricted plasma cells into a variety of organs. Clinical presentation is heterogeneous, and pathophysiological mechanisms of IgG4‐RD remain elusive. There are very few cases of IgG4‐RD with isolated central nervous system manifestation. By leveraging single‐cell sequencing of the cerebrospinal fluid (CSF) of a patient with an inflammatory intracranial pseudotumor, we provide novel insights into the immunopathophysiology of IgG4‐RD. Our data illustrate an IgG4‐RD‐associated polyclonal T‐cell response in the CSF and an oligoclonal T‐cell response in the parenchymal lesions, the latter being the result of a multifaceted cell–cell interaction between immune cell subsets and pathogenic B cells. We demonstrate that CD8+ T effector memory cells might drive and sustain autoimmunity via macrophage migration inhibitory factor (MIF)‐CD74 signaling to immature B cells and CC‐chemokine ligand 5 (CCL5)‐mediated recruitment of cytotoxic CD4+ T cells. These findings highlight the central role of T cells in sustaining IgG4‐RD and open novel avenues for targeted therapies.

Background: IgG4-related disease (IgG4-RD) is a systemic disease characterized by serum IgG4 upregulation, massive infiltration of IgG4-positive plasma cells, and storiform fibrosis, which results in nodules or thickening of the involved organs. Cardiologists have recently recognized that IgG4-RD can be complicated by coronary artery events (CAEs); however, the mechanisms and clinical characteristics of this phenomenon are unknown. We evaluated the clinical signs of patients with coronary periarteritis (CP), aortic periarteritis (AP), and pericardial thickening, which are complications of IgG4-RD, to determine the contributing factors. Methods: We retrospectively examined 19 patients with IgG4-RD who attended or consulted a cardiologist in our department at the University of Tokyo Hospital between January 1, 2004, and December 31, 2021. Results: The frequency of CAEs was significantly higher in the CP group than in the non-CP group. Furthermore, the CP group had significantly lower event-free survival than the non-CP group (log-rank test, P = 0.008). However, the frequency of incidents and event-free survival for CAEs after IgG4-RD diagnosis did not differ significantly between the AP and non-AP groups. Although no statistically significant difference was present between the frequency of CAEs for those with vs without pericardial thickening, the group with pericardial thickening had significantly worse event-free survival than the group without pericardial thickening (log-rank test, P = 0.017). Conclusions: The incidence and clinical course of CAEs complicated by IgG4-RD could be predicted by identifying CP and pericardial thickening in IgG4-RD but not AP. Résumé: Contexte: La maladie liée aux immunoglobulines de type G4 (ML-IgG4) est une maladie généralisée caractérisée par une augmentation du taux sérique d’IgG4, par une infiltration massive de plasmocytes exprimant les IgG4 et par une fibrose storiforme, qui produit des nodules ou un épaississement des organes touchés. Les cardiologues ont récemment reconnu que la ML-IgG4 peut être compliquée par des événements coronariens; les mécanismes et caractéristiques cliniques de ce phénomène demeurent cependant inconnus. Nous avons évalué les signes cliniques chez des patients atteints de périartérite coronarienne (PC), de périaortite (PA) et d’épaississement du péricarde, des complications de la ML-IgG4, pour tenter d’établir les facteurs contributifs. Méthodologie: Nous avons examiné de manière rétrospective les dossiers de 19 patients atteints de ML-IgG4 qui ont été admis à notre service de l’Hôpital de l’Université de Tokyo ou qui ont consulté un cardiologue du service entre le 1er janvier 2004 et le 31 décembre 2021. Résultats: La fréquence des événements coronariens était significativement plus élevée dans le groupe PC que dans les autres groupes. Par ailleurs, le groupe PC avait une survie sans événement significativement plus courte que les autres groupes (test logarithmique par rangs; p = 0,008). En outre, la fréquence des événements coronariens et la survie sans événement coronarien après un diagnostic de ML-IgG4 ne variaient pas de manière significative entre le groupe PA et les autres groupes. Bien qu’aucune différence statistiquement significative n’ait été constatée quant à la fréquence des événements coronariens entre les patients présentant un épaississement du péricarde et les autres patients, le premier groupe affichait une survie sans événement significativement plus courte que l’autre (test logarithmique par rangs; p = 0,017). Conclusions: L’incidence et le déroulement clinique des événements coronariens compliqués par la ML-IgG4 pouvaient être anticipés dans les cas de ML-IgG4 en présence de PC et d’un épaississement du péricarde, mais pas de PA.

IgG4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease whose pathomechanisms remain poorly understood. Here, we identified gene variants in familial IgG4-RD and determined their functional consequences. All 3 affected members of the family shared variants of the transcription factor IKAROS, encoded by IKZF1, and the E3 ubiquitin ligase UBR4. The IKAROS variant increased binding to the FYN promoter, resulting in higher transcription of FYN in T cells. The UBR4 variant prevented the lysosomal degradation of the phosphatase CD45. In the presence of elevated FYN, CD45 functioned as a positive regulatory loop, lowering the threshold for T cell activation. Consequently, T cells from the affected family members were hyperresponsive to stimulation. When transduced with a low-avidity, autoreactive T cell receptor, their T cells responded to the autoantigenic peptide. In parallel, high expression of FYN in T cells biased their differentiation toward Th2 polarization by stabilizing the transcription factor JunB. This bias was consistent with the frequent atopic manifestations in patients with IgG4- RD, including the affected family members in the present study. Building on the functional consequences of these 2 variants, we propose a disease model that is not only instructive for IgG4-RD but also for atopic diseases and autoimmune diseases associated with an IKZF1 risk haplotype. [ABSTRACT FROM AUTHOR]

This article discusses a case of IgG4-related disease (IgG4-RD) with small intestinal involvement. The patient experienced gastrointestinal symptoms and was diagnosed with IgG4-RD based on elevated serum IgG4 levels and diffuse infiltration of IgG4+ plasmacytes in the gastrointestinal tract. Treatment with prednisolone improved the patient's symptoms and resolved the abnormalities seen on CT scans. The article emphasizes the importance of considering IgG4-RD in the diagnosis of chronic gastrointestinal symptoms and highlights the need for histopathological assessment to establish an accurate diagnosis and prevent complications. [Extracted from the article]

Abstract Background Immunoglobulin G4 (IgG4)-related diseases are characterized by abnormal IgG4 levels, swelling, and marked infiltration and fibrosis of the lymphocytes and IgG4-positive plasma cells, causing hypertrophic lesions or nodules. The cause is currently not well understood. IgG4-related diseases involving lesions limited to the pleura are extremely rare. Herein, we report an IgG4-related disease presenting with multiple pleural nodules confirmed by thoracoscopic surgical biopsy. Case presentation A 74 year-old man was referred to our department for definitive diagnosis of multiple pleural nodules after 1 year of follow-up. Computed tomography of the chest revealed multiple pleural nodules, while 2-deoxy-2-( 18F)-fluorodeoxyglucose positron emission tomography imaging exhibited tracer accumulation in the nodules. A thoracoscopic surgical biopsy was performed. Histopathological examination revealed hyalinized fibrous tissue with a high degree of plasma cell-based inflammatory cell infiltration. Immunohistochemically, IgG4-positive cells were conspicuous, accounting for 70.5% of the plasma cells. The postoperative serum IgG4 concentration was 289 mg/dL. We diagnosed the patient with an IgG4-related disease with multiple pleural nodules. The postoperative course was good, and the patient is currently being followed up. Conclusion IgG4-related disease should be considered in cases presenting with multiple pleural nodules.