IgG4-related disease (IgG4-RD) is an immune-mediated condition associated with chronic fibroinflammatory lesions that can affect nearly any organ. IgG4-related hepatobiliary and pancreatic diseases are IgG4-RD involving the hepatobiliary and pancreatic system, which is characterized with elevated serum IgG4 concentrations, large numbers of IgG4 positive lymphoplasma cells infiltration in affected organs, storiform fibrosis, and imaging changes of organ morphology. Due to the lack of reliable biomarkers, histopathology is still an important basis for diagnosis. The pathogenesis of IgG4-related hepatobiliary and pancreatic diseases has not been clarified. This review focuses on the recent advances in intestinal microecology-immunology, host genetics-immunity and recurrence monitoring of IgG4-related hepatobiliary and pancreatic diseases.
Autoimmune Diseases/diagnosis* ; Gastrointestinal Microbiome ; Humans ; Immunoglobulin G ; Immunoglobulin G4-Related Disease/pathology* ; Pancreatic Diseases

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients' clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes. METHODS: We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis. RESULTS: We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils ( P = 0.010), total IgE ( P = 0.006), high-sensitivity C-reactive protein ( P <0.001), erythrocyte sedimentation rate ( P <0.001), complement C4 ( P <0.001), IgG ( P = 0.001), IgG1 (P <0.001), IgG4 (P <0.001), and IgA ( P <0.001), at baseline were significantly different among three subtypes. Compared with proliferative and mixed subtypes, the fibrotic subtype showed the lowest rate of relapse (log-rank P = 0.014). CONCLUSIONS Our study revealed the differences in demographic characteristics, clinical manifestations, organ involvement, laboratory tests, treatment agents, and outcomes across proliferative, fibrotic, and mixed subtypes in the retrospective cohort study. Given significant differences in relapse-free survival among the three subtypes, treatment regimens, and follow-up frequency should be considered separately according to different subtypes.
Humans ; Immunoglobulin G4-Related Disease/pathology* ; Retrospective Studies ; Prospective Studies ; Treatment Outcome ; Immunoglobulin G ; Recurrence

Autoimmune pancreatitis(AIP)is radiologically characterized by sausage-like diffuse swelling of the pancreatic parenchyma but may also be found as a localized mass that is easily misdiagnosed as a pancreatic neoplasm.AIP presenting as multifocal masses is rare.Here we report a case of multifocal IgG4-related AIP,in which the lesions grew in size and finally fused to become radiologically typical.
Humans ; Immunoglobulin G4-Related Disease ; diagnosis ; pathology ; Pancreas ; pathology ; Pancreatic Neoplasms ; Pancreatitis ; diagnosis ; pathology

Objective To investigate the computed tomography(CT)imaging features of IgG4-related kidney disease(IgG4-RKD).Methods The clinicopathological and imaging data of 36 IgG4-RKD patients(including 26 cases of renal parenchyma,10 cases of renal pelvis,24 cases of double kidney or multiple lesions,and 12 cases of single focus)were retrospectively analyzed.Results IgG4-RKD had specific clinicopathological and imaging features.Although the kidney or renal pelvis was involved,there were no common clinical manifestations of malignant tumors such as hydronephrosis and hematuria.The boundary was clear and complete,and it had typical characteristics of continuous progressive enhancement.The peak value was mostly in the solid and excretory phase,and there were no imaging manifestations such as liquefaction,necrosis,cystic degeneration,and calcification.Even if the renal pelvis was obviously involved and the focus was large,there was no invasion of the peripheral renal parenchyma,the shape of the renal pelvis still existed,the wall was smooth,and there was no enlarged peripheral lymph nodes.Conclusions CT images of IgG4-RKD are similar to those of renal malignant tumors.Based on clinicopathological features,CT findings,and blood IgG4-related tests,a definite diagnosis can be made and unnecessary operation can be avoided.
Humans ; Immunoglobulin G ; Immunoglobulin G4-Related Disease/pathology* ; Kidney Neoplasms/pathology* ; Retrospective Studies ; Tomography, X-Ray Computed

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*

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

OBJECTIVE: To comprehend clinical features and patient's physician visit patterns at onset of immunoglobulin G4 related disease (IgG4RD). METHODS: In the study, 100 patients with IgG4RD who received treatments in the Department of Rheumatology and Immunology of Peking University People's Hospital from Apr. 1st, 2017 to Apr. 1st, 2018 were investigated, including gender, age, height, body weight, age of onset, physician visit history, primary history and how did the disease affected their life, etc. RESULTS: In this 100 IgG4RD cohort (57 males and 43 females), the male/female ratio was 1:0.75, the mean age of onset was (51.51±12.9) years, and the median duration was 49 months (ranging from 4 to 231 months). The onset age of males was significantly older than that of females (P<0.01). The manifestations showed that up to 69% patients had submaxillay glands lesion, 59% patients had lacrimal glands lesion, 28% patients had pancreas involvement and 28% patients had parotid glands involvement. The females had more lacrimal glands involvement (P<0.05). 62% patients were complicated with anaphylactic disease. The primary physician visit departments concentrated upon general surgery department (19/100), oral and maxillofacial surgery department (17/100), rheumatology and immunology department (16/100), ophthalmology department (15/100) and gastroenterology department (10/100). The departments where the confirmed diagnose was made concentrated upon rheumatology department (67/100),oral and maxillofacial surgery department (16/100) and gastroenterology department (7/100). The mean diagnosis duration after 2010 was (16.96±2.163) months, significantly shorter than that before 2010, which was (113.3±11.01) months. Before the definite diagnose was made, 43% patients underwent surgeries and 12% patients had more than one time surgeries. The patients whose first-visit department was a surgery department were more likely to undergo surgeries (P<0.01). 18% patients (18/100) stated that the disease had affected their work. CONCLUSION In this cohort of the IgG4RD patients, female is common and has earlier onset age than male. The major manifestations of IgG4RD are salivary glands, lacrimal glands and pancreas involvement. The common chief complains are salivary glands and lacrimal glands enlargement. Accompanied by anaphylactic disease is a marked manifestation of this disease. Delayed diagnoses are not rare, though this situation has been improved since 2010, and more attention still should be paid to the disease.
Adult ; Age of Onset ; Aged ; China ; Cross-Sectional Studies ; Delayed Diagnosis ; Female ; Hospitals, Public ; Humans ; Immunoglobulin G/analysis* ; Immunoglobulin G4-Related Disease/therapy* ; Lacrimal Apparatus/pathology* ; Male ; Middle Aged ; Referral and Consultation ; Salivary Glands/pathology*