Elevated Serum Immunoglobulin G4 Levels Research Articles

7229 A Rare Case of Igg4 Hypophysitis Presenting as Hypogonadotropic Hypogonadism

Abstract Disclosure: C. Dimech: None. G. Jaiswal: None. Hypophysitis is a rare pituitary disorder including a broad range of inflammatory processes which affect the pituitary gland and infundibulum. Previously reported as 1 per 9 million individuals, the true incidence of hypophysitis per year is largely unknown due to the increase of novel etiologies such as immunoglobulin G4 (IgG4)- related disease. IgG4-related hypophysitis (IgG4-RH) was first clinically described in 2004 and later biopsy proven in 2007. The main clinical features are elevated serum IgG4 level and IgG4-positive lymphocyte infiltration of tissues on histopathology. IgG4-RH is reported to account for 1.3% of primary hypophysitis with 3.2:1 incidence ratio of men to women, in the 6th decade of life. Here we present a case of a 68-year-old Caucasian male who presented for evaluation of hypogonadotropic hypogonadism. As fasting morning testosterone levels were significantly low, MRI pituitary was completed which revealed a homogenously enhancing pituitary gland with thickened, nodular enhancement of the pituitary infundibulum. Subsequent lab work-up revealed normal function of remaining anterior pituitary without evidence of central vasopressin deficiency. Evaluation of underlying etiologies was unremarkable except for significantly elevated IgG4 levels (472mg/dL). Based on the significantly elevated IgG-4 levels (>135 mg/dl) and the radiographic findings of the pituitary infundibulum, the diagnosis of possible IgG4-RH was made. The patient was initiated on treatment with rituximab and glucocorticoid therapy with prednisone. Following 3 months of medical therapy, MRI pituitary showed resolution of stalk inflammation, confirming diagnosis of IgG4- RH. Presentation: 6/1/2024

Factors related to elevated serum immunoglobulin G4 (IgG4) levels in a Japanese general population

BackgroundElevated 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.MethodsSerum 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.ResultsThe 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.ConclusionsElevated 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.

Autoimmune pancreatitis: Cornerstones and future perspectives.

Autoimmune pancreatitis (AIP) is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas, leading to inflammation and fibrosis. Although AIP is rare, its incidence is increasing and is often misdiagnosed as other pancreatic diseases. AIP is commonly classified into two types. Type 1 AIP (AIP-1) is typically associated with elevated serum immunoglobulin G4 (IgG4) levels and systemic manifestations, while type 2 AIP is typically a more localized form of the disease, and may coexist with other autoimmune disorders, especially inflammatory bowel diseases. Additionally, there is emerging recognition of a third type (type 3 AIP), which refers to immunotherapy-triggered AIP, although this classification is still gaining acceptance in medical literature. The clinical manifestations of AIP mainly include painless jaundice and weight loss. Elevated serum IgG4 levels are particularly characteristic of AIP-1. Diagnosis relies on a combination of clinical, laboratory, radiological, and histological findings, given the similarity of AIP symptoms to other pancreatic disorders. The mainstay of treatment for AIP is steroid therapy, which is effective in most cases. Severe cases might require additional imm-unosuppressive agents. This review aims to summarize the current knowledge of AIP, encompassing its epidemiology, etiology, clinical presentation, diagnosis, and treatment options. We also address the challenges and controversies in diagnosing and treating AIP, such as distinguishing it from pancreatic cancer and managing long-term treatment, highlighting the need for increased awareness and knowledge of this complex disease.

Spontaneous regression of immunoglobulin G4-related dacryoadenitis and multiple organ involvement: A case report

Immunoglobulin G4 (IgG4)-related dacryoadenitis is rarely resolved spontaneously without steroids. Here, we report a case of IgG4-related dacryoadenitis and extra-ophthalmic lesions with spontaneous regression. This is a clinical case report. A 56-years-old man had a 1-year and 7-month-old histories of neck and eyelid swelling, respectively. On the first examination, the lacrimal and submandibular glands were palpable bilaterally. Computed tomographic images showed enlargement of the lacrimal gland on both sides, right pulmonary hilar lymph node, and pancreas, and thickening of the abdominal aortic wall. Blood tests demonstrated elevated serum IgG4 level and positive hepatitis B surface antibody. Pathological examination of the biopsied lacrimal gland specimens revealed marked IgG4-positive plasma cell infiltration. The patient was monitored carefully without steroid administration. Serum IgG4 level had gradually decreased during follow-up period and reached the normal range 3 years after the biopsy. At 4-year follow-up, the lacrimal and submandibular glands were not palpable on either side. Computed tomographic images demonstrated no enlargement of the lacrimal gland, submandibular gland, or lymph nodes, and improvement of the enlarged pancreas and thickened abdominal aortic wall. Our case indicates that careful observation can be an option in selected cases with risks of steroid treatment or silent clinical course.

Detecting immunoglobulin G4-related intracranial arteriopathy with magnetic resonance vessel wall imaging: a preliminary experience in two cases

BackgroundDetecting immunoglobulin G4 (IgG4)-related intracranial arteriopathy, a rare neurovascular complication of IgG4-related disease, is challenging. While magnetic resonance (MR) vessel wall imaging (VWI) can visualize various neurovascular pathologies, its application to this arteriopathy has not been reported as of this writing.Case presentationA 74-year-old male and a 65-year-old female manifested multiple cranial nerve palsy and neck pain, respectively. Both cases exhibited multiorgan masses with markedly elevated serum IgG4 levels and were clinically diagnosed with IgG4-related disease. Three-dimensional T1-weighted black blood VWI with and without contrast agent identified intracranial vascular lesions characterized as nearly-circumferential mural thickening with homogeneous contrast enhancement in the internal carotid and vertebral arteries; some of the lesions had been unrecognized with screening MR angiography due to expansive remodeling. The former patient underwent corticosteroid therapy, and VWI after treatment revealed decreased mural thickening and enhancement.ConclusionFurther studies to elucidate characteristic findings of VWI might contribute to early detection of this treatable pathology.

It Melts Like Snow: Steroid Responsiveness of Immunoglobulin G4-Related Disease

Dear Editor, A 35-year-old male presented with insidious onset gradually progressive bilateral painless submandibular swelling, followed by periorbital swelling [Figure 1] for the past 7 years. He had no constitutional or sicca symptoms. He had no history of addiction or autoimmunity in the family. Systemic examination was unremarkable. On evaluation, he had raised inflammatory markers with a negative autoimmune panel. Magnetic resonance imaging orbit showed bilateral orbital extraconal soft-tissue masses with contrast enhancement. Incisional biopsy from the extraconal mass was suggestive of fibrocollagenous stroma with aggregation of lymphocytes, plasma cells, and histiocytes without any necrosis or granuloma. On further evaluation, submandibular gland biopsy showed chronic sialadenitis with immunoglobulin G4 (IgG4)-positive plasma cell >10/hpf and IgG4: IgG ratio >40% [Figure 2] without any major organ involvement on imaging. The diagnosis of IgG4-related disease was kept. He was started on oral steroid 0.5 mg/kg/day and observed a rapid clinical response within 15 days of steroid therapy. Later, he was started on azathioprine and continued with tapering dose of steroid. He was followed up every month for first 3 months and then every 3 monthly upto 16 months without any signs of recurrence. For a long-standing indolent disease of 7 years, drastic steroid response with resolution of clinical symptoms was quite evident in our case.Figure 1: (a) Pretreatment bilateral upper eyelid swelling, (b) pretreatment bilateral submandibular swelling, (c and d) during glucocorticoid therapy (day 15) resolution of orbital and submandibular swelling, respectivelyFigure 2: Salivary gland with seromucinous acini and ducts embedded in mildly fibrotic stroma with numerous lymphoid follicles with germinal centers (a and b: H and E). Clusters of plasma cells are highlighted with CD138 immunohistochemical stain (c). IgG4 positive cells, >10/hpf (d)IgG4-related disease (IgG4-RD) is a chronic, systemic, fibroinflammatory condition with variable organ manifestation. CD4+ T-cells and B-cells are central to the pathogenesis causing organ damage and fibrosis. Marked expansion of IgG4-secreting plasmablast in the blood is usually seen in active and untreated cases.[1] Key to diagnosis is the classical histopathological hallmarks of lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. IgG4 RD usually has a good response to steroids but a variable relapse rate. Factors associated with lesser treatment response and relapse were well analyzed in a Japanese multicenter study. Multivariate analysis from the study revealed that intermediate steroid initial dose (0.4–0.69 mg/day), slow tapering regimen (<0.4 mg/day), and shorter disease duration were associated with a significantly lower rate of disease relapse.[2] The study of isolated IgG4 ophthalmic disease also echoed similar results regarding steroid response and relapse, with more relapse in those with elevated serum IgG4 levels and a shorter duration of initial steroid treatment (<5 months). Low-dose steroid maintenance should be considered to avoid recurrence in patients with elevated serum IgG4 levels.[3] Later on, rituximab therapy showed promising results in inducing remission[4] and steroid-free long-term maintenance.[5] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Development of IgG4-related pancreatitis and kidney disease 7 years after the onset of undiagnosed lymphadenopathy: A case report.

This report describes a patient diagnosed with immunoglobulin G4 (IgG4)-related pancreatitis and kidney disease 7 years after the onset of undiagnosed lymphadenopathy. A 48-year-old Japanese woman presented with fatigue and leg oedema. Computed tomography showed perigastric lymphadenopathy, for which she underwent a laparoscopic biopsy of the perigastric lymph nodes. Although histopathological examination of the lymph nodes did not lead to a definitive diagnosis, serological tests revealed elevated serum IgG4 levels (558 mg/dl) and IgG4 immunostaining of the lymph nodes showed IgG4-positive plasma cell infiltration, leading to the suspicion of IgG4-related disease. Further workup revealed no organ lesion other than lymphadenopathy. At age 55 years, despite having no subjective symptoms, contrast-enhanced computed tomography showed low-density lesions in the tail of the pancreas and the left kidney. Histopathological examination showed lymphocyte infiltration, consisting of a mixture of plasma cells and eosinophils, in both organs and obliterative phlebitis in the pancreas. IgG4 immunostaining of the kidney specimens showed 160 IgG4-positive cells per high-powered field, with the IgG4+/IgG+ cell ratio being almost 100%, leading to a diagnosis of IgG4-related pancreatitis and kidney disease. Treatment with prednisolone for 2 months resulted in lesion improvement. Although the diagnosis of IgG4-related lymphadenopathy is often challenging in patients with lymphadenopathy alone, findings in the present patient emphasise the importance of long-term follow-up, as it may allow early detection of involvement of other organs by IgG4-related disease.

Abstract 13337: Increased Serum Immunoglobulin G4 Level is a Novel Predictor of Cardiovascular Events Independent of Established Risk Factors: Results From the Real-cad Study

Background: Inflammation is a mediator of atherosclerosis progression. However, it remains unclear whether immunoglobulin G4 (IgG4)-related immuno-inflammation may play a specific role in cardiovascular disease. Methods: We used a case-cohort design to analyze the association of serum IgG4 levels with future cardiovascular events. The sample included 561 cases of the primary end point, defined as cardiovascular death, myocardial infarction, ischemic stroke, or unstable angina, and a random subcohort of 1688 (1409 males; mean age, 68.1 ± 8.4 years), of whom 73 were also cases, selected from 12413 eligible participants with stable coronary artery disease in the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study. Results: This case-cohort study had a median follow-up of 3.9 years (interquartile range [IR] 2.9-4.6). Serum IgG4 levels at baseline were 45.3 mg/dL (IR 37.9-58.9), and 845 (50%) took high-dose statins in the subcohort sample. In Cox regression using age, gender, statin dose, high-sensitivity C-reactive protein (hsCRP), body mass index, estimated glomerular filtration rate (eGFR), hypertension, diabetes, and serum lipid profiles, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, as covariates, the highest IgG4 quartile was predictive of the primary end point at 4 years (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.03-2.00, P=0.031), compared with the lowest quartile. Similar results were observed for the secondary end point, a composite of the primary end point plus coronary revascularization (HR 1.60, 95% CI 1.16-2.20, P=0.004). Conclusions: Elevated serum IgG4 level at baseline predicted long-term cardiovascular outcomes independent of established risk factors and high-dose statin therapy in patients with stable CAD. Serum IgG4 may reflect residual cardiovascular risk.

A case of eosinophilic granulomatosis with polyangiitis complicated with a similar condition to IgG4 related lung disease

BackgroundAtypical manifestations, such as elevated serum immunoglobulin-G4 (IgG4) and extra-pulmonary IgG4 positive plasmacyte infiltration, have been described in patients with eosinophilic granulomatosis with polyangiitis (EGPA), such complicated situation might not be readily differentiated from IgG4-related disease.Case presentationHere, we report an interesting and rare case of EGPA in a 41 year-old male with negative anti-neutrophil cytoplasmic antibodies (ANCAs), which showed abundant pulmonary IgG4-positive plasma cells infiltration and markedly elevated serum IgG4 levels without extra-pulmonary lesions of IgG4-related disease. The clinical characteristics hesitated us whether the diagnosis as EGPA overlapping with IgG4-related lung disease should be concluded because of the absence of storiform fibrosis and obliterative phlebitis with lymphoplasmacytic infiltration. The patient’s systemic symptoms, pulmonary lesions, blood eosinophils count / percentage, and serum IgG4 levels were significantly improved with immunosuppressive therapy.ConclusionsWe consider that the overlapping pathogenesis exists in the disease course of EGPA and IgG4-related disease, which may lead to interaction during the course of the diseases. And the utilization of diagnostic criteria for IgG4-related lung disease with the careful differentiation is needed in such cases.

Prevalence of Elevated Serum IgG4 Level among Patients Diagnosed or Suspected with Cardiovascular Disorders.

Immunoglobulin G4 (IgG4)-related disease, that is characterized by the elevation of circulating IgG4 level and the tissue-infiltration of IgG4-positive plasma cells, can target the cardiovascular tissue, although the diagnosis of IgG4-related cardiovascular lesion is not easy owing to the substantial risk for the tissue sampling. We herein examined the serum IgG4 levels among cardiac patients. In patients who were admitted to the cardiology department (n=477) and those who underwent computed tomography coronary artery angiography (n=401), elevated serum IgG4 level (≥135 mg/dL) was found 23 (4.8%) and 17 (4.2%), respectively. However, among those with elevated serum IgG4, only two patients could be clinicopathologically diagnosed with IgG4-related disease. Cardiovascular organ involvement may aggravate the prognosis of IgG4-related disease which in general not life-threatening. Considering that the non-negligible prevalence of high IgG4 level among cardiac patients who were not diagnosed with IgG4-related disease, however, physicians should not count too much on the serum IgG4 levels for the diagnosis of IgG4-related cardiovascular lesions, especially when histopathologic findings are not available, or when other-tissue involvement of IgG4-related disease is not apparent. (This is a translation of J Jpn Coll Angiol 2017; 57: 91–98.)

Changes in Serum Immunoglobulin G4 Levels in Patients with Newly Diagnosed Graves' Disease.

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition that can affect almost any organ. We investigated the association between IgG4-RD and the main characteristics of Graves' disease (GD) at the time of diagnosis. Additionally, we evaluated whether serum IgG4 levels change during treatment. Twenty-eight patients with newly diagnosed GD were enrolled into this longitudinal follow-up study. Serum IgG4 levels and thyroid function were measured in all the participants at the time of diagnosis. Further, the serum IgG4 levels of nine of 28 patients with untreated GD were measured after the achievement of euthyroid state (through the use of methimazole). Two (7.1%) of 28 patients with untreated GD had elevated serum IgG4 levels of >135 mg/dL. There was no significant difference in the average IgG4 levels before and after the achievement of euthyroid state (66.2±74.0 mg/dL vs. 50.5±47.3 mg/dL). In two patients, the elevated serum IgG4 levels returned to normal after treatment. However, one patient had an elevated serum IgG4 level of 136.6 mg/dL after treatment. This study showed that serum IgG4 levels varied with treatment in patients with GD, independent of thyroid function, suggesting that IgG4 might be indirectly related to GD.

Potential utility of core needle biopsy in the diagnosis of IgG4-related dacryoadenitis and sialadenitis

IgG4-related disease (IgG4-RD) is a systemic immune-mediated disorder characterized by elevated serum immunoglobulin G4 levels, dense lymphoplasmacytic infiltration, and fibrosis of affected organs...

Mast Cells Exhibiting Strong Cytoplasmic Staining for IgE and High Affinity IgE Receptor are Increased in IgG4-Related Disease

Immunoglobulin G4 (IgG4)-related disease is characterized by elevated serum IgG4 levels and increased numbers of IgG4-positive cells. However, its pathogenesis is not fully understood. We previously suggested that mast cells may play an important role in IgG4-related disease. In this study, we confirmed the characteristics of mast cells in IgG4-related lymphadenopathy by using immunohistochemistry and dual immunofluorescence. We analyzed 23 cases of IgG4-related lymphadenopathy and compared them with 23 cases of non-specific lymphoid hyperplasia. The majority of patients with IgG4-related lymphadenopathy had cervical lesions with involvement of other organs. Immunohistologically, mast cells with strong cytoplasmic staining for immunoglobulin E and high affinity immunoglobulin E receptor were significantly increased in IgG4-related lymphadenopathy as compared to those in non-specific lymphoid hyperplasia (mean: 3.83 ± 3.99 cells per high power field and 7.14 ± 8.21 cells per high power field, respectively; P = 0.007 and P = 0.011). In addition, dual immunofluorescence assay showed that immunoglobulin E and high affinity immunoglobulin E receptor staining exhibited a cytoplasmic granular pattern in IgG4-related lymphadenopathy, suggesting internalization of the antibodies and receptors. Our findings showed that mast cell activation might be involved in the pathogenesis of IgG4-related disease.

Hilar cholangiocarcinoma associated with immunoglobulin G4-positive plasma cells and elevated serum immunoglobulin G4 levels.

Immunoglobulin G4 (IgG4)‐related disease is a fibroinflammatory systemic disorder with multiorgan involvement. Proximal bile duct involvement results in IgG4‐related sclerosing cholangitis, which is characterized by a lymphoplasmacytic infiltrate with abundant IgG4‐positive plasma cells and fibrosis. Differentiating between cholangiocarcinoma and IgG4‐sclerosing cholangitis can present a diagnostic dilemma. We describe an unusual presentation of a hepatic mass meeting multiple criteria for IgG4‐sclerosing cholangitis but was ultimately found to be cholangiocarcinoma. Several published case reports describe patients with suspected cholangiocarcinoma who are later found to have IgG4‐sclerosing cholangitis, but few reports have demonstrated the reverse. Distinguishing between cholangiocarcinoma and IgG4‐sclerosing cholangitis is challenging, and a high clinical suspicion for cholangiocarcinoma must always be maintained. (Hepatology Communications 2018;2:349‐353)

IgG4 related disease (IgG4-RD) as a costochondral mass: A rare presentation

A 39-year-old female came for evaluation for progressive lower costochondral pain and swelling with no associated systemic or constitutional symptoms and no evidence of the involvement of any other organ system. Diagnostic thoracotomy with excision of involved rib and costochondral junction showed plasma cell-rich chronic inflammation with foci of fibrosis with no definite storiform fibrosis or obliterative phlebitis. Immunohistochemistry showed 30%–40% immunoglobulin G4 (IgG4)-positive cells/hpf with an IgG:IgG4 ratio of 30% with sterile cultures and no elevation of serum IgG4 levels. With a presumptive diagnosis of IgG4-related disease, she was started on steroids with which she had complete symptom relief and resolution of the lesion. This case highlights the importance of considering the diagnosis of IgG4 disease even in the absence of typical histopathological findings and elevated serum IgG4 levels. The authors have not found any prior reports in the English literature of IgG4 disease of the ribs and costochondral junction.

IgG4-related disease: a complex under-diagnosed clinical entity.

IgG4-related disease (IgG4-RD) encompasses a spectrum of complex fibro-inflammatory disorders which are often under diagnosed due to unfamiliarity by clinicians. A challenging multitude of clinical manifestations makes the diagnosis cumbersome. The primary clinical feature in IgG4-RD entails a tumor-like presentation coupled with tissue-destructive lesions. Histopathological findings include lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. These findings, in combination with elevated serum immunoglobulin G4 levels, are diagnostic in the setting of single- or multi-organ involvement. A closer understanding of the role of T cells and B cells in the increased production of IgG4 has led to a notion that IgG4 can act as a pathogen, anti-inflammatory agent, or rheumatoid factor. Glucocorticoids are the primary treatment modality; however, relapse is common with prolonged therapy. Alternatively, immunomodulatory agents are being increasingly used as therapy. The aim of this article is to raise awareness of IgG4-RD and review the diagnostic algorithm, as IgG4-RD often mimics a wide array of clinical conditions. In addition, we summarize the pathogenesis and current treatment guidelines of IgG4-RD for clinicians. Awareness and accurate diagnosis are crucial in preventing progression to chronic diseases, thereby diminishing disease-related morbidity and mortality.

Hipofisitis linfoplasmocitaria con expresión de IgG4

Immunoglobulin G4 (IgG4)-related lymphoplasmacytic hypophysitis is a recently known entity. It belongs to the IgG4-related diseases (IgG4-RD), in which one or more organs may be involved, with compressive or obstructive symptoms, or dysfunctionality due to cellular infiltration. The pituitary gland can be isolatedly affected. Clinically, lymphoplasmacytic hypophysitis presents with diabetes insipidus, hypopituitarism and/or symptoms of an occupying sellar mass, being the non-secreting sellar adenomas and other types of hypophysitis the main differential diagnosis. In order to reach the diagnosis, the presence of pituitary enlargement or pituitary stalk thickening on an MRI scan, a distinctive histopathology with positive for IgG4 immunostaining in more than 10 plasma cells per high-power field, and elevated serum IgG4 levels, confirms this type of hypophysitis. As this entity has an excellent response to glucocorticoids, the diagnosis suspicion may avoid an unnecessary surgery in most patients.

網羅的測定による循環器症例における血清IgG4値の検討

Immunoglobulin G4 (IgG4)-related disease, that is characterized by the elevation of circulating IgG4 level and the tissue-infiltration of IgG4-positive plasma cells, can target the cardiovascular tissue, although the diagnosis of IgG4-related cardiovascular lesion is not easy owing to the substantial risk for the tissue sampling. We herein examined the serum IgG4 levels among cardiac patients. In patients who were admitted to the cardiology department (n=477) and those who underwent computed tomography coronary artery angiography (n=401), elevated serum IgG4 level (≥135 mg/dL) was found 23 (4.8%) and 17 (4.2%), respectively. However, among those with elevated serum IgG4, only two patients could be clinicopathologically diagnosed with IgG4-related disease. Cardiovascular organ involvement may aggravate the prognosis of IgG4-related disease which in general not life-threatening. Considering that the non-negligible prevalence of high IgG4 level among cardiac patients who were not diagnosed with IgG4-related disease, however, physicians should not count too much on the serum IgG4 levels for the diagnosis of IgG4-related cardiovascular lesions, especially when histopathologic findings are not available, or when other-tissue involvement of IgG4-related disease is not apparent. (This is a translation of J Jpn Coll Angiol 2017; 57: 91-98.).

Prevalence of IgG-4-associated cholangiopathy based on serum IgG-4 levels in patients with primary sclerosing cholangitis and its relationship with inflammatory bowel disease.

Autoimmune cholangiopathy is part of a fibro-inflammatory immunoglobulin G-4 (IgG-4)-related systemic disease that causes biliary tract strictures. Its clinical presentation is quite similar to that of more common diseases such as primary sclerosing cholangitis (PSC) and pancreatobilliary malignancies. The aims of the present study were to evaluate the prevalence of IgG-4-associated cholangiopathy (IAC) in patients diagnosed with PSC and its relationship with inflammatory bowel disease (IBD). Serum IgG-4 levels were measured in 73 patients. Laboratory data and imaging and endoscopic results were collected from their medical records. The diagnosis of PSC was based on the results of imaging and laboratory data as well as clinical presentation. Serum IgG-4 levels were elevated in 12 patients (16%); half of these patients had IBD. In the group of patients with normal serum IgG-4 levels, 39 patients (63.9%) had IBD (p=0.364). There were no significant statistical differences between PSC patients with normal and elevated serum IgG-4 levels in terms of age, smoking, presence of IBD, extension and severity of IBD, esophageal and gastric varices, Child and the model for end-stage liver disease (MELD) scores, and anatomical location of the biliary stricture (p>0.05). The prevalence of ascites was higher in patients with elevated serum IgG-4 levels (p=0.029). Compared with previous reports, high serum IgG-4 levels were detected in a higher percentage of patients with a preliminary diagnosis of PSC (12% versus 16%). However, there were no clinical or imaging characteristics that could differentiate PSC patients with normal IgG-4 levels from PSC patients with higher IgG-4 levels.

Serum immunoglobulin G4 levels and Graves' disease phenotype.

We investigated, at diagnosis, the relationship between serum immunoglobulin G4 levels and the main characteristics of Graves' disease: hyperthyroidism severity, goiter size, presence of active Graves' ophthalmopathy, antithyroid antibodies status, and titer. This prospective study included 80 newly diagnosed Graves' disease patients. The main parameters measured at diagnosis: thyroid-stimulating hormone, free thyroxine, free triiodothyronine, total triiodothyronine, thyroglobulin, antithyroid peroxidase antibodies, anti-thyroglobulin antibodies, thyroid-stimulating hormone receptor antibodies, immunoglobulin G4. In Graves' disease patients, serum immunoglobulin G4 levels were higher than in general population (p = 0.028) and higher in men compared to women (p = 0.002). Only one female patient with intense hypoechoic goiter, high anti-thyroglobulin antibody, and antithyroid peroxidase antibody titers had an elevated serum immunoglobulin G4 level at diagnosis. Patients with immunoglobulin G4 levels above the 75th percentile (>237.52 mg/dl, N = 20) were younger at Graves' ophthalmopathy onset (p < 0.001), had higher antithyroid peroxidase antibody (p = 0.01), and anti-thyroglobulin antibody levels (p = 0.006) and required shorter duration of the first methimazole treatment cycle (p = 0.041) than patients with immunoglobulin G4 below the 75th percentile. At diagnosis, patients with immunoglobulin G4 levels above the 90th percentile (>286.28 mg/dl, N = 8) had lower total triiodothyronine values (p = 0.001) than patients with IgG below the 90th percentile. No significant correlations were found between smoking status (p = 0.58), goiter size (p = 0.50), the presence of ophthalmopathy (p = 0.42) or thyroid-stimulating hormone receptor antibody titers (p = 0.45) and the mean value of immunoglobulin G4 levels at diagnosis. Our data suggest that Graves' disease patients with elevated immunoglobulin G4 levels at diagnosis have a phenotype characterized by higher anti-thyroglobulin antibody and antithyroid peroxidase antibody titers, less severe T3 hyperthyroidism, younger age at ophthalmopathy onset and require a shorter duration of the first methimazole treatment cycle.