Research on IgG4-related disease (IgG4-RD), an autoimmune condition recognized to be a unique disease entity only two decades ago, has processed from describing patients' symptoms and signs to summarizing its critical pathological features, and further to investigating key pathogenic mechanisms. Challenges in gaining a better understanding of the disease, however, stem from its relative rarity-potentially attributed to underrecognition-and the absence of ideal experimental animal models. Recently, with the development of various high-throughput techniques, "omics" studies at different levels (particularly the single-cell omics) have shown promise in providing detailed molecular features of IgG4-RD. While, the application of omics approaches in IgG4-RD is still at an early stage. In this paper, we review the current progress of omics research in IgG4-RD and discuss the value of machine learning methods in analyzing the data with high dimensionality.
Humans ; Immunoglobulin G4-Related Disease/metabolism* ; Immunoglobulin G/metabolism* ; Machine Learning ; Animals ; Proteomics/methods*

Objective:To investigate the clinical diagnosis and treatment of IgG4-related disease（IgG4-RD） primarily involving the nasal cavity and skull base. Methods:A retrospective analysis was conducted on the clinical data of 8 patients with IgG4-RD primarily involving the nasal cavity and skull base who visited the Nasal and Skull Base Surgery Department at Xiangya Hospital from October 2017 to January 2024. The cohort comprised 4 males and 4 females, aged 8 to 69 years. Clinical data, laboratory examination results, imaging findings, histopathological results, and treatment plans were collected. The clinical manifestations, diagnosis, treatment and follow-up results of IgG4-RD primarily involving nasal cavity and skull base were summarized and previous literature were also reviewed. Results:The initial symptoms in the 8 patients included nasal congestion, headache, sensory function decline, and facial deformities. Three patients also had parotid and pulmonary involvement. Among the 8 patients, 4 underwent partial surgical resection combined with glucocorticoid therapy; 1 underwent partial surgical resection combined with glucocorticoid and immunosuppressant therapy; 1 received glucocorticoid therapy alone; and 2 received glucocorticoid combined with immunosuppressant therapy. Follow-up was conducted one month after treatment, lasting from 5 to 79 months. During the follow-up period, recurrence was observed in 1 patient treated with glucocorticoid combined with immunosuppressants and in 1 patient treated with glucocorticoid alone, while the other 6 patients achieved significant remission. Conclusion:The diagnosis of nasal cavity and skull base IgG4-RD requires the combination of histopathology, laboratory tests, and imaging results. Treatment primarily includes glucocorticoids or combined immunosuppressants. For patients with significant compression symptoms, sensory function impairment, or facial deformities, surgical resection is an important treatment option. Given the high risk of recurrence, early intervention, active treatment, and long-term follow-up are crucial.
Humans ; Male ; Skull Base/pathology* ; Female ; Middle Aged ; Retrospective Studies ; Aged ; Nasal Cavity/pathology* ; Adult ; Immunoglobulin G4-Related Disease/therapy* ; Immunoglobulin G ; Child ; Young Adult ; Adolescent

Objective:To explore the clinical manifestations of IgG4-related diseases（IgG4-RD） complicated with moderately differentiated adenosquamous carcinoma of the parotid gland, the diagnostic criteria for IgG4-related diseases and parotid malignant tumors, treatment regimens, and the application of fine-needle aspiration in disease diagnosis, so as to reduce clinical misdiagnosis and missed diagnosis. Methods:A retrospective analysis was conducted on the case data of a patient with IgG4-related diseases（IgG4-RD） complicated with moderately differentiated adenosquamous carcinoma of the parotid gland admitted to our department in March 2024. The clinical characteristics, imaging findings, preoperative puncture results, and postoperative pathological features were analyzed, and relevant literatures on both diseases were reviewed and summarized. Results:The elderly male patient was admitted due to "a mass in the parotid area in front of the right ear for more than 3 months". Through clinical examination, imaging examination, laboratory examination, and preoperative needle biopsy, the diagnosis of "right parotid moderately differentiated adenosquamous carcinoma complicated with IgG4-related disease" was considered. It was also considered that IgG4-related disease did not involve other organs before surgery, so no systemic hormone therapy was given before or after surgery. After surgery combined with postoperative radiotherapy, follow-up showed that neither the parotid tumor nor IgG4-related disease recurred. Conclusion:"IgG4-related disease complicated with moderately differentiated adenosquamous carcinoma"is a rare clinical disease. Both lack typical clinical manifestations and specific imaging features, and the diagnosis is mostly unclear before surgery. Pathological examination is of great significance in the diagnosis of the disease, while fine-needle aspiration has limited value in the diagnosis, which should attract the attention of clinicians. In addition, for patients with both diseases, individualized treatment plans should be formulated.
Humans ; Parotid Neoplasms/pathology* ; Male ; Carcinoma, Adenosquamous/pathology* ; Immunoglobulin G4-Related Disease/complications* ; Parotid Gland/pathology* ; Retrospective Studies ; Aged ; Biopsy, Fine-Needle ; Immunoglobulin G

Humans ; Larynx ; Immunoglobulin G4-Related Disease ; Immunoglobulin G

Objective: To investigate the value of plasma cells for diagnosing lymph node diseases. Methods: Common lymphadenopathy (except plasma cell neoplasms) diagnosed from September 2012 to August 2022 were selected from the pathological records of Changhai Hospital, Shanghai, China. Morphological and immunohistochemical features were analyzed to examine the infiltration pattern, clonality, and IgG and IgG4 expression of plasma cells in these lymphadenopathies, and to summarize the differential diagnoses of plasma cell infiltration in common lymphadenopathies. Results: A total of 236 cases of lymphadenopathies with various degrees of plasma cell infiltration were included in the study. There were 58 cases of Castleman's disease, 55 cases of IgG4-related lymphadenopathy, 14 cases of syphilitic lymphadenitis, 2 cases of rheumatoid lymphadenitis, 18 cases of Rosai-Dorfman disease, 23 cases of Kimura's disease, 13 cases of dermal lymphadenitis and 53 cases of angioimmunoblastic T-cell lymphoma (AITL). The main features of these lymphadenopathies were lymph node enlargement with various degrees of plasm cell infiltration. A panel of immunohistochemical antibodies were used to examine the distribution of plasma cells and the expression of IgG and IgG4. The presence of lymph node architecture could help determine benign and malignant lesions. The preliminary classification of these lymphadenopathies was based on the infiltration features of plasma cells. The evaluation of IgG and IgG4 as a routine means could exclude the lymph nodes involvement of IgG4-related dieases (IgG4-RD), and whether it was accompanied by autoimmune diseases or multiple-organ diseases, which were of critical evidence for the differential diagnosis. For common lesions of lymphadenopathies, such as Castleman's disease, Kimura's disease, Rosai-Dorfman's disease and dermal lymphadenitis, the expression ratio of IgG4/IgG (>40%) as detected using immunhistochemistry and serum IgG4 levels should be considered as a standard for the possibility of IgG4-RD. The differential diagnosis of multicentric Castleman's diseases and IgG4-RD should be also considered. Conclusions: Infiltration of plasma cells and IgG4-positive plasma cells may be detected in some types of lymphadenopathies and lymphomas in clinicopathological daily practice, but not all of them are related to IgG4-RD. It should be emphasized that the characteristics of plasma cell infiltration and the ratio of IgG4/IgG (>40%) should be considered for further differential diagnosis and avoiding misclassification of lymphadenopathies.
Humans ; Castleman Disease/pathology* ; Plasma Cells/pathology* ; Immunoglobulin G4-Related Disease ; China ; Lymphadenopathy/pathology* ; Inflammation/pathology* ; Lymph Nodes/pathology* ; Diagnosis, Differential ; Lymphadenitis/pathology* ; Immunoglobulin G/metabolism*

IgG4-related disease (IgG4-RD) is a chronic inflammation with fibrosis. About 30% to 40% of patients with IgG4-RD are complicated with atopic manifestations as allergic rhinitis and asthma, usually with elevated serum total immunoglobulin E and peripheral blood eosinophils, which are also of some value for predicting disease activity and relapse. Similar to allergic diseases, activation of type 2 inflammation is also observed in the pathogenesis of IgG4-RD, and eosinophils, basophils, mast cells, thymic stromal lymphopoietin, IL-33, IL-4, IL-5, and IL-13 all participate in the pathogenesis of IgG4-RD. Studies of susceptible genes showed that IgG4-RD and allergic disease shared the same susceptible genes. Monoclonal antibodies targeting type 2 inflammation pathway may become a novel choice for IgG4-RD treatment.
Humans ; Immunoglobulin G4-Related Disease ; Asthma ; Rhinitis, Allergic ; Cytokines ; Inflammation

IgG4-related disease (IgG4-RD) is a chronic inflammation with fibrosis. About 30% to 40% of patients with IgG4-RD are complicated with atopic manifestations as allergic rhinitis and asthma, usually with elevated serum total immunoglobulin E and peripheral blood eosinophils, which are also of some value for predicting disease activity and relapse. Similar to allergic diseases, activation of type 2 inflammation is also observed in the pathogenesis of IgG4-RD, and eosinophils, basophils, mast cells, thymic stromal lymphopoietin, IL-33, IL-4, IL-5, and IL-13 all participate in the pathogenesis of IgG4-RD. Studies of susceptible genes showed that IgG4-RD and allergic disease shared the same susceptible genes. Monoclonal antibodies targeting type 2 inflammation pathway may become a novel choice for IgG4-RD treatment.
Humans ; Immunoglobulin G4-Related Disease ; Asthma ; Rhinitis, Allergic ; Cytokines ; Inflammation

OBJECTIVE: To understand the medical treatment and clinical characteristics of patients with IgG4-related disease (IgG4-RD) with complex clinical manifestations and easy to be misdiagnosed and missed, and to improve the recognition of this disease among doctors from relevant medical departments. METHODS: A retrospective analysis was conducted on the medical records of patients diagnosed with IgG4-RD who were hospitalized and discharged from Peking University Third Hospital from January 1, 2012 to December 31, 2022. The patient' s medical visit status, clinical manifestations, laboratory examinations, diagnosis, and treatment information were summarized. RESULTS: A total of 116 patients diagnosed with IgG4-RD were included in this study, with a male to female ratio of 2. 52∶ 1 and an average age of (61.83±10.80) years. The departments for initial visits were gastroenterology, general surgery, and ophthalmology. While the departments responsible for definitive diagnosis were gastroenterology, rheumatology and immunology, and respiratory medicine. Twenty-one patients (18. 10%) required consultation and treatment from three or more departments before receiving a definitive diagnosis. The median time from symptom onset to the initial clinic visit was 2 (1, 7) months, and the median time from symptom onset to diagnosis was 1 (1, 12) month. Twenty-four patients (20.69%) underwent surgical resection of the affected sites before diagnosis. According to the classification criteria of IgG4-RD, sixty-eight (58.62%) cases were diagnosed definitively, eight (6.9%) cases were likely to be diagnosed, and 40 (34.48%) cases were suspected to be diagnosed. In the 68 definitively diagnosed patients, the most commonly affected organs were submandibular gland, the pancreas, biliary tract, parotid in sequence. The median serum IgG4 (IgG4, immunoglobulin G4) level was 6.16 (3. 61, 12. 30) g/L. Fifty-seven patients (83.82%) were treated with glucocorticoids, and 14 patients (20.59%) were treated with immunosuppressants. The use of immunosuppressants was mainly in the rheumatology and immunology department (78. 57%). CONCLUSION IgG4-RD is more common in elderly males, with submandibular gland, the pancreas, biliary tract, and parotid being most commonly affected. The distribution of initial visit departments in patients is wide. The proportion of definitive diagnosis based on pathology is relatively low. In terms of treatment, the main approach is steroid treatment, while the use of immunosuppres-sants is not widespread.
Humans ; Male ; Female ; Aged ; Middle Aged ; Immunoglobulin G4-Related Disease/diagnosis* ; Retrospective Studies ; Immunosuppressive Agents/therapeutic use* ; Glucocorticoids ; Immunoglobulin G

A case of IgG4-related disease presented with a duodenal ulcer to improve the understan-ding of IgG4-related diseases was reported. A 70-year-old male presented with cutaneous pruritus and abdominal pain for four years and blackened stools for two months. Four years ago, the patient went to hospital for cutaneous pruritus and abdominal pain. Serum IgG4 was 3.09 g/L (reference value 0-1.35 g/L), alanine aminotransferase 554 U/L (reference value 9-40 U/L), aspartate aminotransferase 288 U/L (reference value 5-40 U/L), total bilirubin 54.16 μmol/L (reference value 2-21 μmol/L), and direct bilirubin 29.64 μmol/L (reference value 1.7-8.1 μmol/L) were all elevated. The abdominal CT scan and magnetic resonance cholangiopancreatography indicated pancreatic swelling, common bile duct stenosis, and secondary obstructive dilation of the biliary system. The patient was diagnosed with IgG4-related disease and treated with prednisone at 40 mg daily. As jaundice and abdominal pain improved, prednisone was gradually reduced to medication discontinuation. Two months ago, the patient developed melena, whose blood routine test showed severe anemia, and gastrointestinal bleeding was diagnosed. The patient came to the emergency department of Beijing Hospital with no improvement after treatment in other hospitals. Gastroscopy revealed a 1.5 cm firm duodenal bulb ulcer. After treatment with omeprazole, the fecal occult blood was still positive. The PET-CT examination was performed, and it revealed no abnormality in the metabolic activity of the duodenal wall, and no neoplastic lesions were found. IgG4-related disease was considered, and the patient was admitted to the Department of Rheumatology and Immunology of Beijing Hospital for further diagnosis and treatment. The patient had a right submandibular gland mass resection history and diabetes mellitus. After the patient was admitted to the hospital, the blood test was reevaluated. The serum IgG4 was elevated at 5.44 g/L (reference value 0.03-2.01 g/L). Enhanced CT of the abdomen showed that the pancreas was mild swelling and was abnormally strengthened, with intrahepatic and extrahepatic bile duct dilation and soft tissue around the superior mesenteric vessels. We pathologically reevaluated and stained biopsy specimens of duodenal bulbs for IgG and IgG4. Immunohistochemical staining revealed remarkable infiltration of IgG4-positive plasma cells into duodenal tissue, the number of IgG4-positive cells was 20-30 cells per high-powered field, and the ratio of IgG4/IgG-positive plasma cells was more than 40%. The patient was treated with intravenous methylprednisolone at 40 mg daily dosage and cyclophosphamide, and then the duodenal ulcer was healed. IgG4 related disease is an immune-medicated rare disease characterized by chronic inflammation and fibrosis. It is a systemic disease that affects nearly every anatomic site of the body, usually involving multiple organs and diverse clinical manifestations. The digestive system manifestations of IgG4-related disease are mostly acute pancreatitis and cholangitis and rarely manifest as gastrointestinal ulcers. This case confirms that IgG4-related disease can present as a duodenal ulcer and is one of the rare causes of duodenal ulcers.
Aged ; Humans ; Male ; Abdominal Pain/drug therapy* ; Acute Disease ; Bilirubin ; Duodenal Ulcer/etiology* ; Immunoglobulin G ; Immunoglobulin G4-Related Disease/diagnosis* ; Pancreatitis/drug therapy* ; Positron Emission Tomography Computed Tomography ; Prednisone/therapeutic use* ; Pruritus/drug therapy*

Objective: To analyze the clinicopathological features of IgG4-related diseases (RD) of retroperitoneum and the urinary and male reproductive system (IgG4-RUMR). Methods: A total of 11 IgG4-RUMR cases from January 2013 to March 2021 were retrospectively collected at Peking University Third Hospital and Shandong Provincial Hospital affiliated to Shandong First Medical University. The clinicopathologic features, laboratory and imaging findings were analyzed and scored according to the 2019 ACR/EULAR classification criteria for IgG4-RD. Results: The 11 patients (male:female is 9∶2; mean age 59 years, range from 44 to 83 years) were initially admitted to the Deparment of Urology/Kidney Transplantation (10 cases) and the Department of Oncology (1 case). All patients had urogenital disorders or imaging abnormalities. Three of the 11 patients had a history of IgG4-RD such as lacrimal gland engorgement, salivary gland engorgement and IgG4-associated pancreatitis. Abnormal retroperitoneal soft tissue and hydronephrosis were found in eight cases, while epididymal and spermatic cord masses were found in one case, simple renal mass in one case, and"benign prostatic hyperplasia"in one case. In the 10 patients tested for serum IgG4, the serum IgG4 level was 0.8-14.4 g/L. Histologically, all cases showed significant lymphoplasmacytic infiltration and storiform fibrosis, and some were accompanied by obliterative phlebitis. The number of IgG4 positive plasma cells was 12-155 per high-power field, and the IgG4/IgG ratio was 15%-77%. According to the 2019 ACR/EULAR IgG4-RD classification standard 11 cases scored 20-48 points, all of which met the diagnostic criteria of IgG4-RUMR. Therapeutically, the patient with a simple renal mass underwent partial nephrectomy. The patient with prostate lesion underwent transurethral resection of prostate and was initially diagnosed as nonspecific chronic prostatitis. Later, the patient was admitted again because of salivary gland swelling, and the pathologic diagnosis was amended. The patient with epididymal and spermatic cord masses participated in a clinical trial about retroperitoneal fibrosis. The remaining eight patients received symptomatic treatment such as adhesiolysis and stent placement. All the patients were subsequently treated with glucocorticoid/immunosuppressant and symptoms relieved. Conclusions: IgG4-RUMR is uncommon. In clinical practice, information from clinical, serologic, radiologic and pathologic evaluations must be integrated. IgG4-RUMR should be considered in the differential diagnosis of urinary and male reproductive diseases. The 2019 ACR/EULAR classification criteria for IgG4-RD, while relatively complex, are objective and practical in the diagnosis of IgG4-RUMR.
Adult ; Aged ; Aged, 80 and over ; Autoimmune Diseases/pathology* ; Female ; Glucocorticoids ; Humans ; Immunoglobulin G ; Immunoglobulin G4-Related Disease/pathology* ; Immunosuppressive Agents ; Male ; Middle Aged ; Prostate/pathology* ; Retrospective Studies ; Transurethral Resection of Prostate