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A 76-year-old woman with persistent diarrhea was referred to our hospital. She had purpura, peripheral eosinophilia (18,177/μL), and an elevated serum IgG4 level (819 mg/dL). Abdominal computed tomography revealed massive ascites and bowel edema. A skin biopsy of the purpura revealed leukocytoclastic vasculitis with prominent eosinophilic infiltration. Biopsies of the gastrointestinal mucosa revealed dense eosinophilic infiltration, indicating eosinophilic gastroenteritis (EG) associated with the hypereosinophilic syndrome. The number of IgG4-positive cells increased in the duodenal mucosa; however, the diagnostic criteria for IgG4-related disease (IgG4-RD) were not met. Whether or not EG with ascites is a manifestation of IgG4-RD warrants further investigation.

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., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background and Objectives: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated, fibroinflammatory, multiorgan disease with an obscure pathogenesis. Findings indicating excessive platelet activation have been reported in systemic sclerosis, which is another autoimmune, multisystemic fibrotic disorder. The immune-mediated, inflammatory, and fibrosing intersections of IgG4-RD and systemic sclerosis raised a question about platelets' role in IgG4-RD. Materials and Methods : By borrowing transcriptomic data from Nakajima et al. (GEO repository, GSE66465) we sought a platelet contribution to the pathogenesis of IgG4-RD. GEO2R and BRB-ArrayTools were used for class comparisons, and WebGestalt for functional enrichment analysis. During the selection of differentially expressed genes (DEGs), the translationally active but significantly low amount of platelet mRNA was specifically considered. The platelet-specific gene signature derived was used for cluster analysis of patient and control groups. Results : When IgG4-RD patients were compared with controls, 268 DEGs (204 with increased and 64 with decreased expression) were detected. Among these, a molecular signature of 22 platelet-specific genes harbored genes important for leukocyte-platelet aggregate formation (i.e., CLEC1B , GP1BA , ITGA2B , ITGB3 , SELP , and TREML1 ) and extracellular matrix synthesis (i.e., CLU , PF4 , PPBP , SPARC , and THBS1 ). Functional enrichment analysis documented significantly enriched terms related to platelets, including but not limited to "platelet reactivity", "platelet degranulation", "platelet aggregation", and "platelet activation". During clustering, the 22 gene signatures successfully discriminated IgG4-RD and the control and the IgG4-RD before and after treatment groups. Conclusions : Patients with IgG4-RD apparently display an activated platelet phenotype with a potential contribution to disease immunopathogenesis. If the platelets' role is validated through further carefully designed research, the therapeutic potentials of selected conventional and/or novel antiplatelet agents remain to be evaluated in patients with IgG4-RD. Transcriptomics and/or proteomics research with platelets should take into account the relatively low amounts of platelet mRNA, miRNA, and protein. Secondary analysis of omics data sets has great potential to reveal new and valuable information.

Background: IgG4-related cholangitis (IgG4-SC) and primary sclerosing cholangitis (PSC) are chronic fibro-inflammatory hepatobiliary conditions, with genetic, environmental, and immunologic risk factors, in which epigenetic alterations may provide insights into pathophysiology and novel biomarkers. This study is the first to assess methylation signatures in IgG4-SC., Results: Whole blood DNA methylation profiling and genotyping was performed in 264 individuals; 47 with IgG4-SC, 65 with PSC, 64 with ulcerative colitis (UC), and 88 healthy controls. We identified 19 significant methylation differences between IgG4-SC and controls and 38 between PSC and controls. IgG4-SC and PSC shared 8 probes. Inflammatory genes (including CEP97, IFNAR1, TXK, HERC6, C5orf36, PYY, and MTRNR2L1) were predominantly involved in dysregulated methylation. Epigenetic age acceleration was observed in patients with IgG4-SC, but not in those with PSC or UC. meQTL analyses to identify genetic determinants of methylation revealed a strong human leucocyte antigen (HLA) signal in both PSC and IgG4-SC (HLA-DQB2, HLA-DPA1, HLA-F and HLA-DRA)., Conclusions: We identify novel epigenetic alterations in IgG4-SC and PSC, with biological age acceleration in IgG4-SC, providing insights into disease pathogenesis, and highlight the role of genetic variation especially within the HLA region in shaping the methylome., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval for the study was obtained from the Research Ethics Committee Oxfordshire (10/H0604/51) and the Oxford Radcliffe Biobank (19/SC/0173). Competing interests: EC provides educational material and consults for Amgen (Horizon Therapeutics), Zenus BioPharma, Falk Pharma, Ipsen, Mirum, Intercept, Advance Therapeutics and Moderna. JS has received lecture fees from Takeda and from the Falk Foundation., (© 2024. The Author(s).)

IgG4-related disease is a rare fibroinflammatory condition. Prompt recognition is fundamental to initiate treatment and to prevent organ damage. Diagnostic and classification criteria are primarily intended for use by clinicians with established expertise in IgG4-related disease. Absence of disease awareness among primary care physicians and specialists without expertise in IgG4-related disease remains the main cause of diagnostic delay. We aimed to identify red flags that might increase the suspicion of IgG4-related disease in primary and secondary care settings. A task force of experts in IgG4-related disease from the European Reference Network for Rare Connective Tissue Diseases (ERN-ReCONNET), patient representatives, and primary care physicians derived potential red flags for IgG4-related disease through a systematic literature search and a level of agreement exercise. Five red flags reached 100% agreement among experts: swelling in one or more organ system; pancreatic and biliary tree involvement; increased serum IgG4; IgG4 + plasma cell tissue infiltration; and obliterative phlebitis. Red flags for IgG4-related disease are intended for use in primary and secondary care to improve referral to centres of expertise and prompt early diagnosis., Competing Interests: Declaration of interests GPG received funding from The European Commission within the contract SANTE/2018/B3/030-SI2·813822 to support collaboration with European Reference Network (ERN) ReCONNET as a methodologist in the systematic review on red flags for IgG4-related disease. FF received honoraria from GSK for lectures and plenary presentations at educational events. TA received travel grants from AbbVie and Neovil; declares study support from Janssen; and received honoraria from AbbVie, Amgen, AstraZeneca, GSK, and Neovil for lectures and plenary presentations at educational events. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: Hypocomplementaemia is common in patients with IgG4-related disease (IgG4-RD). We aimed to determine the IgG4-RD features associated with hypocomplementaemia and investigate mechanisms of complement activation in this disease., Methods: We performed a single-centre cross-sectional study of 279 patients who fulfilled the IgG4-RD classification criteria, using unadjusted and multivariable-adjusted logistic regression to identify factors associated with hypocomplementaemia., Results: Hypocomplementaemia was observed in 90 (32%) patients. In the unadjusted model, the number of organs involved (OR 1.42, 95% CI 1.23 to 1.63) and involvement of the lymph nodes (OR 3.87, 95% CI 2.19 to 6.86), lungs (OR 3.81, 95% CI 2.10 to 6.89), pancreas (OR 1.66, 95% CI 1.001 to 2.76), liver (OR 2.73, 95% CI 1.17 to 6.36) and kidneys (OR 2.48, 95% CI 1.47 to 4.18) were each associated with hypocomplementaemia. After adjusting for age, sex and number of organs involved, only lymph node (OR 2.59, 95% CI 1.36 to 4.91) and lung (OR 2.56, 95% CI 1.35 to 4.89) involvement remained associated with hypocomplementaemia while the association with renal involvement was attenuated (OR 1.6, 95% CI 0.92 to 2.98). Fibrotic disease manifestations (OR 0.43, 95% CI 0.21 to 0.87) and lacrimal gland involvement (OR 0.53, 95% CI 0.28 to 0.999) were inversely associated with hypocomplementaemia in the adjusted analysis. Hypocomplementaemia was associated with higher concentrations of all IgG subclasses and IgE (all p<0.05). After adjusting for serum IgG1 and IgG3, only IgG1 but not IgG4 remained strongly associated with hypocomplementaemia., Conclusions: Hypocomplementaemia in IgG4-RD is not unique to patients with renal involvement and may reflect the extent of disease. IgG1 independently correlates with hypocomplementaemia in IgG4-RD, but IgG4 does not. Complement activation is likely involved in IgG4-RD pathophysiology., Competing Interests: Competing interests: The authors declare competing interests with the Rheumatology Research Foundation, NIH, Sanofi, Zenas, Amgen, Genentech, Sana, National Multiple Sclerosis Society, GlaxoSmithKline, Helmsley Charitable Trust, AstraZeneca, Bristol Myers Squibb, Novartis, Alexion Pharmaceuticals, ANI Pharmaceuticals, Aurinia Pharmaceuticals, Exagen Diagnostics, Kypha, Pfizer, UpToDate, The Rheumatology Education Group, Lupus Foundation of America-Heartland Chapter, St Louis Rheumatology Chapter, Lupus Research Alliance, National Scleroderma Foundation, AbbVie, Acepodia, Alpine Immune Sciences, Argenx, Connect Biopharma, CTI BioPharma, Horizon Therapeutics, iCell Gene Therapeutics, IQVIA, Prometheus Biosciences/Merck, Q32 Bio, Salvina Therapeutics, IgG4ward! Foundation, Achillion Pharmaceuticals, Annexon Pharmaceuticals, Arrowhead Pharmaceuticals, Autobahn Therapeutics, Avidity Partners, BioMarin Pharmaceuticals, Broadwing Bio, Celldex Therapeutics, 4D Molecular Therapeutics, HiBIO, Janssen, Kypha, Merck KGaA, Takeda Pharmaceuticals, Compliment Corporation, Gemini Therapeutics, Leducq Foundation, Be Bio Pharma, Paratus, Octagon Therapeutics, Ab Pro, Viela Bio, MedPace and BioCryst., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: In 2018, diagnostic criteria were introduced for IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis (PA/RPF). This study assessed the existing criteria and formulated an improved version., Methods and Results: Between August 2022 and January 2023, we retrospectively analyzed 110 Japanese patients diagnosed with IgG4-related disease (IgG4-RD) involving cardiovascular and/or retroperitoneal manifestations, along with 73 non-IgG4-RD patients ("mimickers") identified by experts. Patients were stratified into derivation (n=88) and validation (n=95) groups. Classification as IgG4-RD or non-IgG4-RD was based on the 2018 diagnostic criteria and various revised versions. Sensitivity and specificity were calculated using experts' diagnosis as the gold standard for the diagnosis of true IgG4-RD and mimickers. In the derivation group, the 2018 criteria showed 58.5% sensitivity and 100% specificity. The revised version, incorporating "radiologic findings of pericarditis", "eosinophilic infiltration or lymphoid follicles", and "probable diagnosis of extra-PA/-RPF lesions", improved sensitivity to 69.8% while maintaining 100% specificity. In the validation group, the original and revised criteria had sensitivities of 68.4% and 77.2%, respectively, and specificities of 97.4% and 94.7%, respectively., Conclusions: Proposed 2023 revised IgG4-related cardiovascular/retroperitoneal disease criteria show significantly enhanced sensitivity while preserving high specificity, achieved through the inclusion of new items in radiologic, pathological, and extra-cardiovascular/retroperitoneal organ categories.

Primary Sjögren's syndrome (pSS) is an autoimmune disease, with B cell hyperactivation and autoantibody production as its immunological hallmarks. Although the distinction between immunoglobulin G4-related disease (IgG4-RD) and pSS, based on the presence or absence of certain autoantibodies, seems easy to make, possibility of elevated serum IgG4 concentration and often similar organ involvement may lead to a misdiagnosis. The increased serum concentration of IgG4 in IgG4-RD is not clearly linked to the pathogenesis of IgG-RD and it has been suggested that it may constitute just an epiphenomenon. The aim of this article is to discuss the presence of IgG4 in pSS and IgG4-RD and its potential significance for these two diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Maslinska and Kostyra-Grabczak.)

Background: Elevated serum immunoglobulin G4 (IgG4) concentrations are one of the characteristic findings in IgG4-related disease (IgG4-RD). This study investigated the frequency of elevated serum IgG4 levels and associated factors in a general Japanese population., Methods: Serum IgG4 concentrations were measured in 1,201 residents of Ishikawa prefecture who underwent general medical examinations. Factors associated with elevated serum IgG4 concentrations were assessed by logistic regression analysis. Participants with elevated serum IgG4 were subjected to secondary examinations., Results: The mean serum IgG4 concentration was 44 mg/dL, with 42 (3.5%) participants having elevated serum IgG4 levels. Age- and sex-adjusted logistic regression analyses showed that male sex, older age, and lower intake of lipids and polyunsaturated fatty acids and higher intake of carbohydrates in daily diet were associated with elevated serum IgG4 concentration. Subgroup analyses in men showed that older age, lower estimated glomerular filtration rates based on serum cystatin C (eGFR-cysC) levels, and higher hemoglobin A1c (HbA1c) levels were associated with elevated serum IgG4 concentration. Analyses in women showed that lower intake of lipids and fatty acids and higher intake of carbohydrates were significantly associated with elevated serum IgG4 concentration. One of the 15 participants who underwent secondary examinations was diagnosed with possible IgG4-related retroperitoneal fibrosis., Conclusions: Elevated serum IgG4 levels in a Japanese general population were significantly associated with older age, male gender, and dietary intake of nutrients, with some of these factors identical to the epidemiological features of IgG4-RD., (© 2024. The Author(s).)

Objectives: Our study aimed to investigate the distinct clinical patterns of seronegative IgG4-related disease (IgG4-RD) patients., Methods: We retrospectively enrolled 698 treatment-naïve IgG4-RD patients in this study. Patients were divided into four different subgroups according to their baseline serum IgG4 levels. The distinct clinical patterns of seronegative IgG4-RD patients were revealed through the comparison of baseline clinical data and disease prognosis among the different subgroups. COX regression analyses were used to investigate the risk factors for disease relapse and to construct the nomogram model., Results: Seronegative IgG4-RD patients account for a minority of IgG4-RD patients (49/698, 7.02%). The proportions of seronegative IgG-RD patients in our study and several Asian cohorts were significantly lower than those of the European and American cohorts. Seronegative IgG4-RD patients got lower serum IgG levels (p < 0.0001), lower eosinophil count (p < 0.0001), lower serum IgE levels (p < 0.0001)), lower IgG4-RD responder index (RI) scores (p < 0.0001), and fewer affected organ numbers (p < 0.0001) compared with other subgroups, whereas they were more likely to manifest fibrotic type with some special organ involvement. Younger age at onset, GCs monotherapy, elevated C-reactive protein level, and elevated erythrocyte sedimentation rate level are the risk factors for the disease relapse of seronegative IgG4-RD patients. An effective nomogram model predicting disease relapse of seronegative IgG4-RD patients was constructed. Seronegative IgG4-RD patients with scores >84.65 at baseline were susceptible to suffering from disease relapse., Conclusions: Distinct clinical features and multiple risk factors for disease relapse of seronegative IgG4-RD patients have been revealed in this study. A nomogram model was constructed to effectively predict disease relapse during the follow-up period., (© 2024 The Association for the Publication of the Journal of Internal Medicine.)

Background: IgG4-related disease is a multiorgan fibroinflammatory disease considered to have an autoimmune origin. Case series describing individual organ involvement have suggested differences in phenotypic expression between males and females. We aimed to characterise differences in IgG4-related disease manifestations between male and female patients in a large single-centre cohort., Methods: In this retrospective, single-centre cohort study, patients were recruited from the Massachusetts General Hospital Rheumatology Clinic (Boston, MA, USA) and classified according to the American College of Rheumatology-European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria. Only patients satisfying the ACR-EULAR classification criteria were included in the study. Data on age at diagnosis, organ involvement at baseline, treatment status, and pre-treatment laboratory values were collected. Circulating plasmablasts and B-cell subsets were quantitated by flow cytometry. Active disease was defined by an IgG4-related disease Responder Index score of more than 0. Laboratory values were analysed for patients who were untreated at baseline and had active IgG4-related disease. The main outcomes were assessed in all participants with available data., Findings: Of the 564 participants enrolled in the Massachusetts General Hospital Rheumatology Clinic IgG4-related disease Registry, 328 fulfilled ACR-EULAR classification criteria and were included between January, 2008, and May, 2023. There was a strong male predominance (male:female ratio 2·2:1) with 226 (69%) males and 102 (31%) females, which contrasted markedly with our general rheumatology clinic population (0·4:1; p<0·001). The male predominance increased with each decade of life starting at age 40 years. On average, male patients were 5·5 years older at diagnosis than female patients (63·7 years vs 58·2 years; p=0·0031). We observed male patients to have higher ACR-EULAR classification criteria scores at baseline with a median score of 35·0 (IQR 28·0-46·0), compared with 29·5 (25·0-39·0) for females (p=0·0010). The proportion of male patients with pancreatic and renal involvement was almost double the proportion observed in female patients (50% of the male patients had pancreatic involvement, compared with about 26% of the female patients; p<0·0001). Male patients were more likely to have serological abnormalities at baseline. The distribution of IgG4 values differed significantly between male an female sexes, favouring higher values in males. We found that male patients with IgG4-related disease were more likely to have active B-cell responses in the blood as defined by plasmablast expansions., Interpretation: IgG4-related disease is unusual among autoimmune diseases in that it is more likely to affect males than females and to present with a striking sex-dependent organ distribution and degree of B-cell response. These findings highlight important variation between IgG4-related disease and other conditions generally believed to have an autoimmune basis. Most autoimmune diseases, by contrast to IgG4-related disease, demonstrate pronounced predilections for affecting females more frequently than males. Hypotheses surrounding the cause and pathophysiology of this condition need to consider this unusual sex distribution among patients with IgG4-related disease., Funding: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases., Competing Interests: Declaration of interests YGHB reports honorarium from Otsuka-Visterra for continuing medical education and Grand Rounds lectures on autoimmune pancreatitis. ZSW reports consulting fees from Viela Bio, Zenas, Horizon, Sanofi, MedPace, BioCryst, and Amgen; and participation on a Data Safety Monitoring Board or Advisory Board for Sanofi, Horizon, Novartis, Shionogi, and Otsuka-Visterra. SP reports consultancy fees from Be Bio Pharma, Paratus, and Octagon Therapeutics; and stock options for Ab Pro, Be Bio Pharma, and Paratus. JHS reports consultancy fees from Acepodia, Alexion, Bristol Myers Squibb, Connect Biopharma, Horizon, iCell Gene Therapeutics, Q32, Sanofi, and ZenasBio; has a role as Principal Investigator in a phase 3 clinical trial (inebilizumab); and is a consultant for Horizon (now Amgen) on IgG4-related disease. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Type 1 autoimmune pancreatitis (AIP) is a pancreatic manifestation of IgG4-related disease (IgG4-RD). Although AIP and IgG4-RD are characterized by multiple organ involvement including salivary glands, lung, and kidney, co-occurrence of chronic rhinosinusitis (CRS) and AIP/IgG4-RD has been poorly defined., Objective: We explored molecular mechanism accounting for the co-occurrence of CRS and AIP/IgG4-RD., Methods: Serum concentrations of IFN-α and IL-33 were measured by enzyme-linked immune-sorbent assay., Results: We encountered a patient with concurrent type 1 AIP/IgG4-RD and CRS. Induction of remission by prednisolone (PSL) for type 1 AIP/IgG4-RD led to a marked improvement of CRS. Serum cytokine analysis after PSL treatment revealed a marked reduction in serum concentrations of IFN-α and IL-33, both of which are candidate pathogenic cytokines for AIP/IgG4-RD., Conclusions: Given that IL-33 is shared as one of pathogenic cytokines by type 1 AIP/IgG4-RD and CRS, enhanced IL33 responses may cause concurrent type 1 AIP/IgG4-RD and CRS.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a chronic, immune-mediated condition characterized by fibro-inflammatory lesions with lymphoplasmacytic infiltration. Diagnosis traditionally relies on histopathological findings, including the presence of IgG4+ plasma cells. However, due to challenges in biopsy accessibility, additional measures are needed to facilitate diagnosis., Objectives: To identify additional parameters for characterizing IgG4-RD patients., Methods: We compared several circulating factors between a cohort of patients with IgG4-RD disease seen at our hospital between 2017 and 2023 and healthy controls., Results: Among 16 suspected patients, 13 were confirmed to have IgG4-RD, and 3 were classified as highly likely. Comparison with controls revealed differences in white blood cell count (WBC) (Folf change (FC) 1.46, P < 0.05), plasmablasts (FC 3.76, P< 0.05), plasmablasts CD38 (FC 1.43, P < 0.05), and CD27 (FC 0.66, P = 0.054), thus highlighting potential markers for IgG4-RD diagnosis. Treatments with steroids/rituximab tend to reduce plasmablast (FC 0.6) and IgG4 (FC 0.28) levels and to increase Gal-3 levels., Conclusions: Levels of plasmablasts are a significant diagnostic feature in IgG4-RD. Healthy individuals have a lower level of plasmablasts. Elevated Gal-3 in serum of patients with IgG4-RD suggests a role in plasmablast activation. CD38/CD27 expression by plasmablasts emerges as a potential marker. Further research on a larger cohort is needed to confirm these findings.

Background: The goal was to explore the cognition of diagnosis and treatment level of IgG4-related diseases mainly involving lymph nodes., Methods: The clinical manifestations, laboratory indicators, histopathology, and therapeutic effects of a patient with IgG4-RD suspected of lymphoma were analyzed and the relevant literature was reviewed., Results: Lymph node biopsy showed reactive hyperplasia of lymph node tissue. The liver biochemical indexes were abnormal and the bone marrow smear showed atypical lymphocytes. Lymph node section: IgG4+ cells > 100/HPF (IgG4/IgG > 40%). The serum IgG4 level was 17,200 mg/L, and the diagnosis was IgG4-RD. Oral glucocorticoids took effect after 2 weeks, and no significant enlargement of lymph nodes was observed., Conclusions: For the diagnosis of IgG4-RD, at present, histopathology is still the gold standard, but a single result cannot diagnose the disease. Comprehensive judgment should be made by combining clinical symptoms, serum IgG4 level and imaging results to prevent misdiagnosis and missed diagnosis, and to avoid over-diagnosis. Short-term hormonal diagnostic therapy may be used in highly suspected patients who cannot be diagnosed. Once diagnosed, standardized medication, adhere to follow-up, regular review, to prevent recurrence and adverse drug reactions.

Background: Detection of IgG subclasses (IgGSc) is vital for the diagnosis and management of disease, especially IgG4-related diseases (IgG4-RD). This study aimed to evaluate the performances of the chemiluminescent immunoassay (CLIA) for detecting IgGSc and diagnosing IgG4-RD by IgGSc., Methods: A total of 40 individuals with IgG4-RD, 40 with primary Sjogren's syndrome (pSS), and 40 healthy controls (HCs) were enrolled. Serum samples were collected for the simultaneous detection of IgG1, IgG2, IgG3, and IgG4 by the Siemens immunonephelometric assay and the CLIA. The correlation analysis was performed, and diagnostic value was analyzed by the receiver operating characteristic (ROC) curve., Results: Patients with IgG4-RD had higher IgG4 (p < 0.001) and lower IgG1 (p < 0.001) than those with pSS, and HC. The results by the Siemens immunonephelometric assay and the CLIA showed a strong correlation in detecting IgG1, IgG2, IgG3, and IgG4 (r = 0.937, r = 0.847, r = 0.871, r = 0.990, all p < 0.001, respectively). The sum of IgG1, IgG2, IgG3, and IgG4 using two assays strongly correlated with total IgG by the IMMAGE 800 (r = 0.866, r = 0.811, both p < 0.001, respectively). For discriminating IgG4-RD from pSS and HC, no significant differences were observed in CLIA IgG4 and Siemens immunonephelometric assay IgG4 (z = 0.138, p = 0.891), which provided the area under the curves (AUCs) of 0.951 (p < 0.001) and 0.950 (p < 0.001), respectively. The AUCs of CLIA IgG1 and Siemens immunonephelometric assay IgG1 in distinguishing pSS from IgG4-RD and HC were 0.761 (p < 0.001) and 0.765 (p < 0.001), respectively, with no significant differences (z = 0.228, p = 0.820)., Conclusions: The CLIA and the Siemens immunonephelometric assay appeared to have good consistency with comparable diagnostic value in detecting IgGSc, especially IgG4, and IgG1 that can accurately identify IgG4-RD or pSS in clinical practice., (© 2024 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Coronary artery wall contrast enhancement (CE) has been applied to non-invasive visualization of changes to the coronary artery wall in systemic lupus erythematosus (SLE). This study investigated the feasibility of quantifying CE to detect coronary involvement in IgG4-related disease (IgG4-RD), as well as the influence on disease activity assessment., Methods: A total of 93 subjects (31 IgG4-RD; 29 SLE; 33 controls) were recruited in the study. Coronary artery wall imaging was performed in a 3.0 T MRI scanner. Serological markers and IgG4-RD Responder Index (IgG4-RD-RI) scores were collected for correlation analysis., Results: Coronary wall CE was observed in 29 (94 %) IgG4-RD patients and 22 (76 %) SLE patients. Contrast-to-noise ratio (CNR) and total CE area were significantly higher in patient groups compared to controls (CNR: 6.1 ± 2.7 [IgG4-RD] v. 4.2 ± 2.3 [SLE] v. 1.9 ± 1.5 [control], P < 0.001; Total CE area: 3.0 [3.0-6.6] v. 1.7 [1.5-2.6] v. 0.3 [0.3-0.9], P < 0.001). In the IgG4-RD group, CNR and total CE area were correlated with the RI (CNR: r = 0.55, P = 0.002; total CE area: r = 0.39, P = 0.031). RI´ scored considering coronary involvement by CE, differed significantly from RI scored without consideration of CE (RI v. RI´: 15 ± 6 v. 16 ± 6, P < 0.001)., Conclusions: Visualization and quantification of CMR coronary CE by CNR and total CE area could be utilized to detect subclinical and clinical coronary wall involvement, which is prevalent in IgG4-RD. The potential inclusion of small and medium-sized vessel involvements in the assessment of disease activity in IgG4-RD is worthy of further investigation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)