IgG4-related Disease Research Articles

IgG4-related Renal Disease Case Report and Review of Literature

IgG4-related Renal Disease Case Report and Review of Literature

Immunoglobulin G4-related thoracic disease: clinical and radiological findings of a Turkish cohort.

Thoracic involvement of Immunoglobulin G4-related disease (IgG4-RD) is relatively rare and may be disregarded at the time of initial diagnosis due to its asymptomatic nature. This study aimed to ascertain the prevalence and patterns of thoracic involvement in a retrospective cohort of Turkish patients with IgG4-RD. A total of 90 patients (47 males and 43 females, with a mean age of 57.7±15.5 years) diagnosed with IgG4-RD were reviewed retrospectively. All computed tomography (CT) scans were re-evaluated by two thoracic radiologists and IgG4-related thoracic disease was assessed on four compartments: The mediastinum, pulmonary parenchyma, airways, and pleura. IgG4-related thoracic disease was categorized as: definite, highly probable, probable or possible. There were 64 patients who had undergone at least one thorax CT examination, and 18 (28%) were diagnosed with IgG4-related thoracic disease. The rate of IgG4-related thoracic disease increased by 20% and reached a ratio of 48.4% (n=31) after a thorough reevaluation of registry data specifically to thoracic findings. The mediastinum was the most frequently involved compartment, affecting 16 (51.6%) patients, followed by pulmonary parenchyma in 14 (45.2%) patients, and airways and pleura in 10 (32.3%) patients each. Other organ involvements were more prevalent and IgG4 levels were higher in patients with thoracic involvement. Eosinophils were significantly elevated in patients with thoracic involvement (p=0.023). IgG4-related thoracic disease is heterogeneous and likely to be more prevalent than currently recognized. The mediastinum is the most frequently involved compartment. It is important to assess IgG4-related thoracic disease at the time of initial diagnosis. Elevated levels of serum IgG4 and eosinophils, as well as a greater number of organ involvements may serve as indicators of thoracic involvement.

Unraveling the Clinical Features and Outcomes of IgG4-Related Ophthalmic Disease.

Background/Objectives: IgG4-related ophthalmic disease (IgG4-ROD), characterized by lymphoplasmacytic infiltration, fibrosis, and elevated IgG4 levels, presents diagnostic challenges while offering insights into immune-mediated inflammatory disorders. The aim of this study was to comprehensively examine the clinical features and outcomes of IgG4-ROD. Materials and Methods: A retrospective study was conducted on 33 patients diagnosed with IgG4-ROD, fulfilling the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. The demographic characteristics of the IgG4-ROD patients were compared with those of 37 patients diagnosed with IgG4-related disease (IgG4-RD) in departments other than ophthalmology (IgG4-nonROD) at the same hospital during the same period. The patients diagnosed with IgG4-ROD were initially treated with glucocorticosteroid (GCS) monotherapy, GCS combined with steroid-sparing agents (SSAs; mycophenolate mofetil, azathioprine, hydroxychloroquine), biologic agent (rituximab) monotherapy, or watchful waiting. The primary outcome was the assessed treatment response at 6 months, and the secondary outcome was the evaluation of recurrence at 1 year after initial treatment. A response was evaluated as the absence of ocular signs and symptoms, either clinically or radiologically. Results: Eyelid swelling (17 patients, 51.5%) was the most common symptom, and lacrimal gland (17 patients, 51.5%) was the most frequent site of involvement. The response rate for GCS monotherapy was 33.3% (3 out of 9 patients), while the response rate for GCS combined with SSA was 60.0% (9 out of 15 patients). The lacrimal gland group demonstrated a significantly higher treatment response compared to the non-lacrimal gland group (66.7% vs. 20.0%, p = 0.013), and the combination of GCS and SSA resulted in a significantly higher treatment response than the GCS monotherapy (77.8% vs. 33.3%, p = 0.045). The group including hydroxychloroquine (HCQ), which comprised 5 out of 33 patients (15.2%), showed no recurrence at 1 year. Conclusions: The combination therapy of GCS and SSA for IgG4-ROD can be considered an effective treatment approach and HCQ could be considered as a potential adjunctive therapy for IgG4-ROD.

Revealing the distinct clinical patterns and relapse risk factors in seronegative IgG4-RD patients: A retrospective cohort study over a decade.

Our study aimed to investigate the distinct clinical patterns of seronegative IgG4-related disease (IgG4-RD) patients. 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. 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. 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.

Implications of Serum IgG4 Levels for Pancreatobiliary Disorders and Cancer.

Background/Objectives: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated disorder presenting as mass-like lesions with obstructions. An elevated serum IgG4 level is identified in more than half of affected patients and is considered a diagnostic criterion. IgG4-RD is still easily misdiagnosed as neoplastic or infectious disease. We aimed to conduct a hospital-based study to illuminate the association between serum IgG4 levels and pancreatobiliary disorders and cancer. Methods: In this study, serum IgG4 levels were assessed at our hospital's immunology laboratory, utilizing data from the hospital's computer center, and the diagnostic codes used were based on ICD-9-CM. We analyzed IgG4 level data collected between April 2013 and April 2020, including patients' age, gender, and diseases, but excluding the rationale for IgG4 level assessment. Employing propensity score matching (PSM) at a 1:1 ratio to mitigate age and gender confounding, we analyzed 759 patients divided into groups by IgG4 levels (≤140 and >140 mg/dL; and ≤140, 141-280, >280 mg/dL). We explored associations between IgG4 levels and conditions such as pancreatobiliary cancer (the group included cholangiocarcinoma, pancreatic cancer, and ampullary cancer), cholangitis, cholangiocarcinoma, pancreatitis, pancreatic cancer, and ampullary cancer. Results: Our study analyzed the demographics, characteristics, and serum IgG4 levels of participants and found no significant differences in serum IgG4 levels across various pancreatobiliary conditions. Nevertheless, the crude odds ratios (ORs) suggested a nuanced association between a higher IgG4 level > 280 mg/dL and increased risks of cancer and pancreatitis, with crude ORs of 1.52 (p = 0.03) and 1.49 (p = 0.008), respectively. After PSM matching, the further analysis of 759 matched patients showed no significant differences in IgG4 levels > 140 mg/dL between cancerous and non-cancerous groups, nor across other pancreatobiliary conditions. A higher serum IgG4 level > 280 mg/dL was significantly associated with pancreatobiliary cancer and cholangiocarcinoma, with crude ORs of 1.61 (p = 0.026) and 1.62 (p = 0.044), respectively. In addition, IgG4 > 280 mg/dL showed a greater association with pancreatic cancer compared with 141-280 mg/dL, with crude OR of 2.18 (p = 0.038). Conclusions: Our study did not find a clear association between serum IgG4 levels (>140 mg/dL) and pancreatobiliary cancer. We observed that higher IgG4 levels (>280 mg/dL) may be associated with cholangiocarcinoma and pancreatic cancer, as indicated by crude ORs. However, the adjusted analysis did not demonstrate the significant association between IgG4 level > 280 mg/dL and cancer. Considering IgG4-RD as a chronic and persistent inflammatory status, it is more closely associated with inflammatory diseases than with cancer. Therefore, further long-term cohort studies are necessary to evaluate the potential role of IgG4 levels in cancer risk among these patients.

Systematic analysis for clinical characteristics and outcomes of IgG4-related disease patients during the COVID-19 pandemic.

To systematically describe clinical characteristics and investigate factors associated with COVID-19-related infection, hospital admission, and IgG4-related disease relapse in IgG4-RD patients. Physician-reported IgG4-RD patients were included in this retrospective study. Using multivariable logistic regression analysis to determine factors for primary outcome (COVID-19-related IgG4-RD relapse) and secondary outcome (COVID-19-related infection and hospital admission). Covariates included age, sex, body mass index, smoking status, comorbidities, IgG4-RD clinical features, and treatment strategies. Among 649 patients, 530 had a diagnosis of COVID-19, 25 had COVID-19-related hospital admission, and 69 had COVID-19-related IgG4-RD relapse. Independent factors associated with COVID-19 infection were age (OR, 0.98; 95% CI, 0.96-1.00), body mass index (1.10, 1.03-1.18), and tofacitinib (0.34, 0.14-0.79). Further analysis indicated that age (1.10, 1.03-1.16), coronary heart disease (24.38, 3.33-178.33), COVID-19-related dyspnea (7.11, 1.85-27.34), pulmonary infection (73.63, 16.22-4615.34), and methotrexate (17.15, 1.93-157.79) were associated with a higher risk of COVID-19-related hospital admission. Importantly, age (0.93, 0.89-0.98), male sex (0.16, 0.03-0.80), ever/current smoking (19.23, 3.78-97.80), COVID-19-related headache (2.98, 1.09-8.17)andpsychiatric symptoms (3.12, 1.07-9.10), disease activity before COVID-19 (1.89, 1.02-3.51), number of involved organs (1.38, 1.08-1.76), glucocorticoid dosage (1.08, 1.03-1.13), and methotrexate (5.56, 1.40-22.08) were strong factors for COVID-19-related IgG4-RD relapse. Our data add to evidence that smoking and disease-specific factors (disease activity, number of involved organs, and specific medications) were risk factors of COVID-19-related IgG4-RD relapse. The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate and increasing glucocorticoid dosages in the COVID-19 era. Key Points • COVID-19-related infection or hospital admission were associated with known general factors (age, body mass index, specific comorbidities and methotrexate) among IgG4-RD patients. • Smoking and disease-specific factors (disease activity, number of involved organs and specific medications) were associated with higher odds of COVID-19-related IgG4-RD relapse. • The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate or increasing glucocorticoid dosages.

Tubulointerstitial nephritis with storiform fibrosis in a patient with angioimmunoblastic T-cell lymphoma.

We present a case of an angioimmunoblastic T-cell lymphoma (AITL) and tubulointerstitial nephritis with storiform fibrosis in a 76-year-old man. The patient exhibited lymphadenopathy, polyclonal hypergammaglobulinemia, and renal dysfunction and was diagnosed with AITL on the basis of lymph node biopsy findings. The serum IgG4 level was highly elevated. Renal biopsy revealed IgG4-positive plasma cells and storiform fibrosis without infiltration of AITL, and the findings indicated IgG4-related kidney disease (IgG4-RKD). Following THPCOP therapy for AITL, the renal function improved. While diagnosing IgG4-RKD in a patient with AITL poses challenges, follicular helper T cell involvement appeared crucial in AITL and renal tubulointerstitial lesions in this case.

IKZF1 and UBR4 gene variants drive autoimmunity and Th2 polarization in IgG4-related disease.

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.

Efficacy and safety of rituximab induction therapy and effect of rituximab maintenance for IgG4-related disease: a systematic review and meta-analysis

BackgroundPrevious studies have reported that rituximab (RTX) therapy might be beneficial in reducing relapse rates in patients with IgG4-related disease (IgG4-RD). Therefore, we aimed to systematically assess the efficacy and safety of RTX induction treatment and the effect of RTX maintenance in patients with IgG4-RD. MethodsThe protocol was registered in the PROSPERO (CRD42023427352). PubMed, Embase, the Cochrane database, Scopus, and the Web of Science were interrogated to identify studies that evaluated the impact of RTX on prognosis in IgG4-RD. We explored the impact of various subgroups of factors on relapse outcomes and focused on the possible role of maintenance therapy in reducing relapse rates. The pooled incidence of adverse events of RTX therapy and the influencing factors have also been evaluated. ResultsEighteen studies comprising 374 patients (mean age 56.0 ± 8.7 years; male 73.7 %) with a mean follow-up duration of 23.4 ± 16.3 months were included. The pooled estimate of the response rate, complete remission rate, overall relapse rate, adverse event rate, and serious adverse event rate of RTX induction therapy were 97.3 % (95 % CI, 94.7 %–99.1 %), 55.8 % (95 % CI, 39.6 %–71.3 %), 16.9 % (95 % CI, 8.7 %–27.1 %), 31.6 % (95 % CI, 16.7 %–48.9 %) and 3.9 % (95 % CI, 0.8 %–8.9 %), respectively. In subgroup analysis, the pooled relapse rate was significantly lower in studies with maintenance than without maintenance (2.8% vs 21.5 %, p < 0.01). Pooled Kaplan-Meier relapse curves also demonstrated that RTX maintenance therapy provided a better prognosis. ConclusionsRTX induction therapy appears to have satisfactory efficacy in the induction of remission in IgG4-RD. In addition, prophylactic RTX maintenance therapy after induction may be beneficial in preventing relapse of IgG4-RD.

Clinical characteristics of chronic sclerosing sialadenitis as a distinctive entity from primary Sjögren's syndrome.

This study aimed to elucidate the clinical and laboratory differences between chronic sclerosing sialadenitis (CSS) and primary Sjögren's syndrome (pSS), highlighting CSS as a distinct pathological entity within the spectrum of salivary gland pathology. This retrospective, single-center study was conducted at Seoul St. Mary's Hospital between January 2000 and December 2022. Patients diagnosed with CSS via salivary gland biopsy were included, and those with IgG4-related disease (IgG4-RD) or other confounding factors were excluded. Clinical and laboratory CSS profiles were compared with those of a control group of patients with typical pSS from the Korean Initiative of Primary Sjögren's Syndrome (KISS) prospective cohort study. Twenty-one with CSS and 501 patients with pSS from Seoul St. Mary's Hospital were retrospectively analyzed. Patients with CSS were older at diagnosis, had a lower prevalence of ocular symptoms, and exhibited distinct immunological markers compared to those with pSS. Logistic regression analysis revealed that anti-Ro antibody positivity, elevated erythrocyte sedimentation rate levels, low serum complement 3 levels, and accompanying dry eye symptoms were factors distinguishing pSS from CSS. Even after excluding IgG4-RD, CSS was significantly different from pSS in terms of clinical and laboratory findings. Recognition of these differences is crucial for the accurate diagnosis and management of CSS, underscoring its status as a distinct pathological entity among salivary gland pathologies.

Pathogenic roles of follicular helper T cells in IgG4-related disease and implications for potential therapy.

IgG4-related disease (IgG4-RD) is a recently described autoimmune disorder characterized by elevated serum IgG4 levels and tissue infiltration of IgG4+ plasma cells in multiple organ systems. Recent advancements have significantly enhanced our understanding of the pathological mechanism underlying this immune-mediated disease. T cell immunity plays a crucial role in the pathogenesis of IgG4-RD, and follicular helper T cells (Tfh) are particularly important in germinal center (GC) formation, plasmablast differentiation, and IgG4 class-switching. Apart from serum IgG4 concentrations, the expansion of circulating Tfh2 cells and plasmablasts may also serve as novel biomarkers for disease diagnosis and activity monitoring in IgG4-RD. Further exploration into the pathogenic roles of Tfh in IgG4-RD could potentially lead to identifying new therapeutic targets that offer more effective alternatives for treating this condition. In this review, we will focus on the current knowledge regarding the pathogenic roles Tfh cells play in IgG4-RD and outline potential therapeutic targets for future clinical intervention.

Immunoglobulin G4-related disease -related Disease: What a Clinician Needs to Know

Immunoglobulin G4-related disease -related Disease: What a Clinician Needs to Know

Secondary diabetes due to different etiologies: Four case reports

BACKGROUND As research on diabetes continues to advance, more complex classifications of this disease have emerged, revealing the existence of special types of diabetes, and many of these patients are prone to misdiagnosis and underdiagnosis, leading to treatment delays and increased health care costs. The purpose of this study was to identify four causes of secondary diabetes. CASE SUMMARY Secondary diabetes can be caused by various factors, some of which are often overlooked. These factors include genetic defects, autoimmune disorders, and diabetes induced by tumours. This paper describes four types of secondary diabetes caused by Williams–Beuren syndrome, Prader–Willi syndrome, pituitary adenoma, and IgG4-related diseases. These cases deviate significantly from the typical progression of the disease due to their low incidence and rarity, often leading to their neglect in clinical practice. In comparison to regular diabetes patients, the four individuals described here exhibited distinct characteristics. Standard hypoglycaemic treatments failed to effectively control the disease. Subsequently, a series of examinations and follow-up history confirmed the diagnosis and underlying cause of diabetes. Upon addressing the primary condition, such as excising a pituitary adenoma, providing glucocorticoid supplementation, and implementing symptomatic treatments, all patients experienced a considerable decrease in blood glucose levels, which were subsequently maintained within a stable range. Furthermore, other accompanying symptoms improved. CONCLUSION Rare diseases causing secondary diabetes are often not considered in the diagnosis of diabetes. Therefore, it is crucial to conduct genetic tests, antibody detection and other appropriate diagnostic measures when necessary to facilitate early diagnosis and intervention through proactive and efficient management of the underlying condition, ultimately improving patient outcomes.

IgG4-associated disease with systemic lupus erythematosus: A case report and review.

We report a 67-year-old man who presented with poor dietary intake and fatigue. Laboratory tests showed leukopenia, antinuclear antibody (ANA) positivity, anti-dsDNA antibody (A-dsDNA) and anti-Smith antibody (anti-Sm) negativity, decreased C3 and C4, elevated serum immunoglobulin G (IgG), IgG4, and creatinine, and 1.25 g urinary protein at 24 hours. As his condition worsened, re-examination showed thrombocytopenia and A-dsDNA positivity, and renal biopsy pathology showed IgG4-related tubulointerstitial nephritis. The final diagnosis was IgG4-related disease (IgG4-RD) with systemic lupus erythematosus (SLE). His condition improved with glucocorticoid (GC) combined with hydroxychloroquine (HCQ) and mycophenolate mofetil (MMF) treatment. This case highlights that IgG4-RD and SLE may occur successively or co-exist and may convert into each other.

Primary pulmonary angiosarcoma was misdiagnosed as IgG4-related disease by needle biopsy: A challenging case report

Primary pulmonary angiosarcoma was misdiagnosed as IgG4-related disease by needle biopsy: A challenging case report

Sinonasal immunoglobulin G4-related disease: a case report of an atypical and rare entity

BackgroundImmunoglobulin G4-related disease is marked by extensive inflammation and fibrosis of an unknown autoimmune component, with an overall incidence ranging from 0.78 to 1.39 per 105 person-years. Sinonasal immunoglobulin G4-related disease is atypical and exceedingly uncommon in the existing literature, frequently manifesting clinically as chronic rhinosinusitis, epistaxis, and facial pain.Case presentationThis report describes a 25-year-old Iraqi female who has been suffering from symptoms of chronic rhinosinusitis for 8 years. Despite undergoing several surgeries, there has been no improvement in her symptoms. A tissue biopsy that revealed dense lymphoplasmocytosis with noticeable plasma cell infiltration, storiform fibrosis, and obliterative angitis, along with positive immunohistochemical staining for Immunoglobulin G4 plasma cells, finally confirmed the diagnosis of sinonasal immunoglobulin G4-related disease. The patient responded well to oral prednisolone and methotrexate treatments.ConclusionsThe main objective of the current report is to raise awareness among physicians about the significance of promptly identifying and diagnosing this rarity, thus preventing the adverse consequences linked to delayed diagnosis and treatment initiation.

Imaging findings in a rare case of alveolar, hepatic and splenic sarcoidosis presenting with thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is an acute haematological disorder characterized by severe ADAMTS13 enzyme deficiency, leading to consumptive thrombocytopenia, mechanical haemolysis, and organ damage. Its association with multisystemic sarcoidosis is extremely rare and, to the best of our knowledge, described in only two cases so far. We present the case of a 52-year-old woman with TTP and antibodies anti-ADAMTS13, showing computed tomography (CT) and magnetic resonance imaging (MRI) evidence of pulmonary, hepatic, and splenic lesions initially reported as ischemic/inflammatory changes. A follow-up MRI of the abdomen revealed increased evidence of the liver lesions, focal intrahepatic bile duct dilatation, splenic lesions, and enlarged hepatic hilar nodes. The follow-up chest CT showed increased evidence of the parenchymal lung consolidations. Given the radiological persistence of those alterations and the history of TTP, the hypothesis of an IgG4-related disease was then made. The IgG4 levels were found to be normal, while the histological examination of the liver revealed non-necrotizing granulomatous chronic inflammation. Elevated levels of angiotensin-converting enzyme were found, and the QuantiFERON-TB Gold test was negative for tuberculosis infection. Thus, the overall clinical picture was consistent with multisystemic sarcoidosis (alveolar, hepatic, and splenic). The diagnosis of sarcoidosis, already challenging due to the variability of its clinical presentation, can become even more complicated when it manifests with uncommon haematological manifestations such as TTP, along with non-specific extra-pulmonary involvement. While imaging aids in documenting organ damage, the definitive diagnosis of sarcoidosis necessitates histologic confirmation of noncaseating granulomas and the exclusion of other possible granulomatous diseases.

Immunoglobulin G4-related disease mimicking an appendiceal neoplasm: a case report.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by chronic activation of the immune system and a tendency to form tumorous lesions. IgG4-RD is frequently characterized by the presence of tumor-like masses affecting multiple organs and is easily mistaken for a malignant neoplasm. However, IgG4-RD affecting the appendix is extremely rare, with only seven cases reported previously. We report the case of a woman in her early 60s who presented with insidious abdominal pain and radiological findings mimicking appendiceal neoplasms. After diagnosing appendiceal neoplasms, surgery was performed. The patient had a serum IgG4 concentration of <1.35 g/L, which did not satisfy one of the three revised comprehensive diagnostic criteria for IgG4-RD. A pathological examination was conducted, and the patient was diagnosed with appendiceal IgG4-RD. To the best of our knowledge, there have been no previously reported cases of IgG4-RD affecting the appendix in patients with low serum IgG4 concentrations. This report may prove beneficial for the future understanding of IgG4-RD and for the revision of diagnostic and treatment strategies.

WED-152 Design and study population of MITIGATE: the first multinational randomized controlled clinical trial in IgG4 related disease, evaluating the efficacy and safety of the CD19 B cell depleting agent inebilizumab

WED-152 Design and study population of MITIGATE: the first multinational randomized controlled clinical trial in IgG4 related disease, evaluating the efficacy and safety of the CD19 B cell depleting agent inebilizumab

Clinicopathological features of immunoglobulin G4-related constrictive pericarditis

AimConstrictive pericarditis (CP) is characterised by scarring fibrosis and a loss of pericardial elasticity, which causes heart failure. IgG4 (immunoglobulin G4)-related disease (IgG4-RD) is a systemic fibro-inflammatory disease characterised by the infiltration of IgG4-immunopositive plasmacytes and high serum IgG4 levels that frequently shape tumorous lesions. Although pericardial involvement of IgG4-RD is rare, with indications of CP, pericardial effusion and irregular masses, the clinical and pathological features remain unclear. In this study, we examined the relationship between CP and IgG4-RD. MethodsAmong 35 thick-walled CP cases (histologically pericardial thickening ≥2 mm), eight cases were aetiology identified. Using the diagnostic criteria for IgG4-RD, 11 cases were classified as IgG4-CP, whereas the remainder were considered true idiopathic CP (16 cases) and the clinical pathological features were evaluated. ResultsCompared with the other groups, the IgG4-CP group was more common in men and associated with low-grade fever and massive pericardial effusion with frequent recurrence. Deaths resulting from heart failure occurred in a few cases of the IgG4-CP group, but not in other groups. An increase in C-reactive protein and a high positivity rate of anti-nuclear antibodies frequently occurred in the IgG4-CP group. Histologically, the IgG4-CP group included lymphoid follicle, eosinophil infiltration and few calcifications. ConclusionsPericardial IgG4-RD occurs not only as nodular lesions, but also as thick-walled CP, and accounts for approximately 40% of thick-walled CP cases of unknown cause. The predominant clinical characteristic was refractory and recurrent pericardial effusion. Recognising IgG4-RD as a cause of CP is important to initiate appropriate therapy.