scholarly journals Serum checkpoint molecules in patients with IgG4-related disease (IgG4-RD)

2021 ◽  
Author(s):  
Haruki Matsumoto ◽  
Yuya Fujita ◽  
Naoki Matsuoka ◽  
Jumpei Temmoku ◽  
Makiko Furuya-Yashiro ◽  
...  
Keyword(s):  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Immunoglobulin G4 ◽  
Clinical Phenotypes ◽  
Related Disease ◽  
Visceral Involvement ◽  
Igg4 Related Disease ◽  
Serum Igg4 ◽  
Significant Difference

Abstract Background Immunoglobulin G4-related disease (IgG4-RD) is characterized by increased serum IgG4 concentration and infiltration of IgG4+ plasma cells in the affected organs. The present study aimed to characterize the serum levels of coinhibitory checkpoint molecule, T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3), and its ligand, galectin-9 (Gal-9), among IgG4-related disease in patients with IgG4-RD patients with various organ involvements. Methods Serum samples were collected from untreated 59 patients with IgG4-RD, 116 patients with rheumatoid arthritis, and 37 healthy controls. Patients with IgG4-RD (n = 57) were subdivided into those with visceral involvement (n = 38) and those without visceral involvement (n = 21). Serum levels of Gal-9 and soluble TIM-3 (sTIM-3) were determined using enzyme-linked immunosorbent assay (ELISA). Results were compared with the clinical phenotypes of IgG4-RD. Results In untreated patients with IgG4-RD, serum levels of Gal-9 and sTIM-3 were significantly higher than in RA patients as well as in healthy controls. There were significant correlations between serum levels of Gal-9 or sTIM-3 and serum levels of IgG, BAFF, or sIL-2R. However, there was no significant correlation between the serum levels of Gal-9 or sTIM-3 and serum IgG4 concentrations. Serum levels of sTIM-3 were significantly higher in a subset of patients with visceral involvements than in those without visceral involvements. However, there was no significant difference in the serum levels of Gal-9 between IgG4-RD patients with and without visceral involvements. Although both, Gal-9 and sTIM-3 were elevated in untreated IgG4-RD patients, and the levels of these checkpoint molecules remained unchanged after steroid therapy. Conclusion Serum levels of Ga-9 and sTIM-3 were significantly elevated in untreated patients with IgG-RD. Furthermore, serum levels of sTIM-3 were significantly higher in IgG4-RD patients with visceral involvements. These checkpoint molecules could be a potentially useful biomarker for IgG4-RD and for assessing the clinical phenotypes of IgG4-RD.

scholarly journals Serum checkpoint molecules in patients with IgG4-related disease (IgG4-RD)

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Haruki Matsumoto ◽  
Yuya Fujita ◽  
Naoki Matsuoka ◽  
Jumpei Temmoku ◽  
Makiko Yashiro-Furuya ◽  
...  
Keyword(s):  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Immunoglobulin G4 ◽  
Clinical Phenotypes ◽  
Related Disease ◽  
Visceral Involvement ◽  
Igg4 Related Disease ◽  
Serum Igg4 ◽  
Significant Difference

Abstract Background Immunoglobulin G4-related disease (IgG4-RD) is characterized by increased serum IgG4 concentration and infiltration of IgG4+ plasma cells in the affected organs. The present study aimed to characterize the serum levels of coinhibitory checkpoint molecule, T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3), and its ligand, galectin-9 (Gal-9), among IgG4-related disease in patients with IgG4-RD patients with various organ involvements. Methods Serum samples were collected from untreated 59 patients with IgG4-RD, 13 patients with rheumatoid arthritis, and 37 healthy controls (HCs). HCs lacked chronic medical diseases or conditions and did not take prescription medications or over-the-counter medications within 7 days. Patients with IgG4-RD (n = 57) were subdivided into those with visceral involvement (n = 38) and those without visceral involvement (n = 21). Serum levels of Gal-9 and soluble TIM-3 (sTIM-3) were determined using enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical phenotypes of IgG4-RD. Results In untreated patients with IgG4-RD, serum levels of Gal-9 and sTIM-3 were significantly higher than in RA patients as well as in healthy controls. There were significant correlations between the serum levels of Gal-9 or sTIM-3 and serum levels of IgG, BAFF, or sIL-2R. However, there was no significant correlation between the serum levels of Gal-9 or sTIM-3 and serum IgG4 concentrations. Serum levels of sTIM-3 were significantly higher in a subset of patients with visceral involvements than in those without visceral involvements. However, there was no significant difference in the serum levels of Gal-9 between IgG4-RD patients with and without visceral involvements, although both Gal-9 and sTIM-3 were elevated in untreated IgG4-RD patients, and the levels of these checkpoint molecules remained unchanged after steroid therapy. Conclusion Serum levels of Gal-9 and sTIM-3 were significantly elevated in untreated patients with IgG4-RD. Furthermore, serum levels of sTIM-3 were significantly higher in IgG4-RD patients with visceral involvements. These checkpoint molecules could be a potentially useful biomarker for IgG4-RD and for assessing the clinical phenotypes of IgG4-RD.

scholarly journals Serum immunoglobulin free light chains and their association with clinical phenotypes, serology and activity in patients with IgG4-related disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eduardo Martín-Nares ◽  
Vanessa Saavedra-González ◽  
Reynerio Fagundo-Sierra ◽  
Blanca Estela Santinelli-Núñez ◽  
Teresa Romero-Maceda ◽  
...  
Keyword(s):  
Renal Involvement ◽  
Serum Levels ◽  
Serum Immunoglobulin ◽  
Light Chains ◽  
Free Light Chains ◽  
Cross Sectional ◽  
Clinical Phenotypes ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Head Neck

AbstractThe clinical utility of serum immunoglobulin free light chains (sFLC) in IgG4-related disease (IgG4-RD) is unknown. Herein we evaluated their association with clinical phenotypes, serology and activity in patients with IgG4-RD. Cross-sectional study that included 45 patients with IgG4-RD, and as controls 25 with Sjögren’s syndrome (SS) and 15 with sarcoidosis. IgG4-RD patients were classified in clinical phenotypes: pancreato-hepato-biliary, retroperitoneum/aorta, head/neck-limited and Mikulicz/systemic; as well as proliferative vs. fibrotic phenotypes. We assessed the IgG4-RD Responder Index (IgG4-RD RI) at recruitment and measured IgG1, IgG4, κ and λ sFLC serum levels by turbidometry. sFLC levels were similar among IgG4-RD, SS and sarcoidosis groups. Regarding the IgG4-RD patients, the mean age was 49 years, 24 (53.3%) were men and 55.5% had activity. Eight (17.7%) belonged to pancreato-hepato-biliary, 6 (13.3%) to retroperitoneum/aorta, 14 (31.1%) to head/neck-limited, 16 (35.5%) to Mikulicz/systemic phenotypes, whereas 36 (80%) to proliferative and 9 (20%) to fibrotic phenotypes. High κ sFLC, λ sFLC and κ/λ ratio were present in 29 (64.4%), 13 (28.9%) and 13 (28.9%) of IgG4-RD patients, respectively. There were no differences in sFLC among IgG4-RD phenotypes. κ sFLC and κ/λ ratio correlated positively with the number of involved organs and IgG4-RD RI. Patients with renal involvement had higher κ sFLC and λ sFLC. The AUC for κ sFLC and λ sFLC, for renal involvement was 0.78 and 0.72, respectively. Active IgG4-RD had higher levels of κ sFLC and more frequently a high κ/λ ratio. The AUC for κ sFLC and κ/λ ratio for predicting active IgG4-RD was 0.67 and 0.70, respectively. sFLC correlated positively with IgG1 and IgG4 levels. sFLC may be useful as a biomarker of disease activity as well as multiorgan and renal involvement. In particular, a high κ/λ ratio may identify patients with active disease.

scholarly journals Anti-phosphatidylserine/prothrombin Complex Antibodies in Patients With Cutaneous Vasculitis: Possible Involvement in the Pathogenesis

2020 ◽  
Author(s):  
Yuto Tamura ◽  
Tamihiro Kawakami ◽  
Yupeng Dong ◽  
Miku Yoshinari ◽  
Yuka Nishibata ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Systemic Vasculitis ◽  
Serum Levels ◽  
Cutaneous Vasculitis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Iga Vasculitis ◽  
Skin Involvement ◽  
Wild Type ◽  
Significant Difference

Abstract Objective. It was previously demonstrated that cutaneous vasculitis, including IgA vasculitis and cutaneous arteritis (CA), is associated with the presence of IgM antibodies (Abs) against the phosphatidylserine/prothrombin complex (PS/PT). Recently, novel enzyme-linked immunosorbent assay kits for the detection of IgG and IgM anti-PS/PT (aPS/PT) Abs have become commercially available.Methods. The prevalence of serum IgG and IgM aPS/PT Abs in both cutaneous and systemic vasculitis was determined using these kits. In addition, to examine whether aPS/PT Abs were involved in the pathogenesis of cutaneous vasculitis, inbred wild-type rats were intravenously administered with a rat IgM class aPS/PT monoclonal Ab established previously or with rat immunoglobulins as controls. To express PS on the surface of vascular endothelium, these rats were given a subcutaneous injection of cell-free histones (250 µg/ml, 300 µl/site) 2 hours in advance. Results. Serum IgM aPS/PT Ab levels were elevated in patients with systemic vasculitis with skin involvement and CA compared to those in patients with systemic vasculitis without skin involvement and healthy controls. There was no significant difference in the serum levels of IgG aPS/PT Abs between the patients and healthy controls. Correspondingly, inbred wild-type rats intravenously administered with the aPS/PT monoclonal IgM Ab after appropriate priming—subcutaneous histone injection—developed cutaneous vasculitis. Some rats given rat IgM instead of the aPS/PT monoclonal Ab also developed cutaneous vasculitis, whereas vasculitis did not occur in rats given IgG or only priming by histones. Conclusion. IgM aPS/PT Abs could be involved in the pathogenesis of cutaneous vasculitis.

scholarly journals Immunoglobulin G4-related disease - diagnostic dilemma and importance of clinical judgement: a case report

2020 ◽  
Vol 8 (11) ◽  
pp. 4144
Author(s):  
Jagadeesh Chandrasekaran ◽  
Phani Krishna Machiraju
Keyword(s):  
Early Recognition ◽  
Elevated Serum ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Inflammatory Disorder ◽  
Imaging Features ◽  
Immunoglobulin G4 ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Serum Igg4 ◽  
The Right

Immunoglobulin G4 (IgG4)-related disease is a multi-organ, immune-mediated, fibro-inflammatory disorder characterized by tumefactive masses in the affected organs. Incidence and prevalence of IgG4-related disease (RD) are not clearly known and have slight male preponderance. It often involves multiple organs at the time of presentation or over the course of disease mimicking malignancy, Sjogren's syndrome, antineutrophil cytoplasmic antibodies associated vasculitis, infections. A thorough workup is needed to rule out these mimickers. A 33-year-old gentleman presented to us with history of progressive swelling in the right peri-orbital region for four years. On evaluation, abdominal imaging was notable for the sausage-shaped pancreas and hypoenchancing nodules in bilateral kidneys. Histological examination of right lacrimal gland revealed lymphoplasmacytic infiltrate and storiform fibrosis. Serum IgG4 levels were normal, and immunostaining was negative. A diagnosis of IgG4-RD was suggested because of multi-organ involvement, classical radiological and histopathological features. Awareness about IgG4-RD, an under-recognized entity is essential, as it is treatable, and early recognition may help in a favourable outcome. Appropriate use of clinicopathological, serological and imaging features in the right clinical context may help in accurate diagnosis. Elevated serum IgG4 levels and biopsy are not mandatory for the diagnosis.

scholarly journals Clinical phenotypes of IgG4-related disease reflect different prognostic outcomes

Rheumatology ◽  
2020 ◽  
Vol 59 (9) ◽  
pp. 2435-2442 ◽  
Author(s):  
Marco Lanzillotta ◽  
Corrado Campochiaro ◽  
Gaia Mancuso ◽  
Giuseppe Alvise Ramirez ◽  
Gabriele Capurso ◽  
...  
Keyword(s):  
Cumulative Dose ◽  
Disease Onset ◽  
Recurrence Time ◽  
Clinical Judgement ◽  
Clinical Phenotypes ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Serum Igg4 ◽  
Group 3 ◽  
Group 1

Abstract Introduction Four clinical phenotypes of IgG4-related disease (IgG4-RD) have been recently identified by latent class analysis (LCA): pancreato-biliary (group 1); retroperitoneum/aortitis (group 2); head and neck limited (group 3); and Mikulicz/systemic (group 4). The reproducibility of this classification in clinical practice and its relevance for patient management, however, remain unknown. Methods The study included 179 patients. Four IgG4-RD experts were asked to classify a validation cohort of 40 patients according to published LCA-derived phenotypes based on clinical judgement. Agreement between LCA and clinical clustering was calculated. To assess differences among disease phenotypes, the following variables were recorded on an additional 139 patients: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD responder index (RI); history of atopy, diabetes, osteoporosis, relapses and malignancy; cumulative dose of glucocorticoids; and use of rituximab. Results Clinical judgement replicated LCA classification with strong agreement among IgG4-RD experts (κ = 0.841, P < 0.0005). At disease onset, group 1 showed the highest levels of serum IgG4 and IgE. Groups 2 and 4 had the lowest and highest IgG4-RD RI, respectively. At 2 years’ follow-up, group 3 received the highest cumulative dose of glucocorticoids, but higher incidences of diabetes mellitus were observed in groups 1 and 4, consistent with the higher likelihood of pancreatic involvement in groups 1 and 4. No difference among the four groups was observed in terms of disease recurrence, time to relapse and frequency of rituximab infusion. Conclusion Clinical phenotypes of IgG4-RD reflect differences in epidemiological features and prognostic outcomes.

Thoracic Involvement in IgG4-Related Disease

2020 ◽  
Vol 41 (02) ◽  
pp. 202-213 ◽  
Author(s):  
Marta Casal Moura ◽  
Ria Gripaldo ◽  
Misbah Baqir ◽  
Jay H. Ryu
Keyword(s):  
Clinical Laboratory ◽  
Wide Spectrum ◽  
The Body ◽  
Obliterative Phlebitis ◽  
Immunoglobulin G4 ◽  
Related Disease ◽  
First Line Therapy ◽  
Igg4 Related Disease ◽  
Serum Igg4 ◽  
Histopathologic Features

AbstractImmunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that has been recognized to involve virtually any organ in the body and typically manifests mass-like lesions (tumefactive). Although initial reports of this disease (autoimmune pancreatitis [AIP]) were described in the Japanese population, it has since been reported worldwide. It is most commonly seen in adults of middle age or older, more often men than women. The pathogenesis of IgG4-RD is largely unknown, but genetic factors, microorganisms, and autoimmunity are thought to play important roles. Serum IgG4 concentration is elevated in the majority of patients with IgG4-RD but is a nonspecific finding. Characteristic histopathologic features include dense lymphoplasmacytic infiltrate, fibrosis (often in storiform pattern), and obliterative phlebitis. Lung involvement in IgG4-RD was first reported in 2004 in two patients with AIP and coexisting interstitial lung disease. Since then, a wide spectrum of intrathoracic involvement has been reported and includes not only parenchymal lung diseases but also pleural, airway, vascular, and mediastinal lesions. Thoracic involvement in IgG4-RD is often found incidentally during the workup of extrathoracic lesions but can sometimes be the presenting abnormality. The diagnosis of IgG4-RD requires correlation of clinical, laboratory, imaging, and histopathologic features. Glucocorticoids are the first-line therapy but other options including B cell depletion are being investigated. IgG4-RD is generally associated with an indolent clinical course and most patients improve with glucocorticoid therapy.

Immunoglobulin G4, Autoimmune Pancreatitis and Pancreatic Cancer

2014 ◽  
Vol 33 (1) ◽  
pp. 86-90 ◽  
Author(s):  
Martina Bojková ◽  
Petr Dítě ◽  
Jana Dvořáčková ◽  
Ivo Novotný ◽  
Katarina Floreánová ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Steroid Therapy ◽  
Autoimmune Pancreatitis ◽  
Normal Limit ◽  
Serum Levels ◽  
Pancreatic Tissue ◽  
Immunoglobulin G4 ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Igg4 Level

Background: Immunoglobulin G4 (IgG4)-related diseases are a group of diseases characterized by enlargement of the affected organs, elevation of serum IgG4, massive infiltration of affected organs with lymphocytes and plasma cells with IgG4 positivity and tissue fibrosis. Type I autoimmune pancreatitis is one form of IgG4-related disease. For IgG4-related diseases, various localizations are described for up to 10% of malignancies. The aim of our study was to examine IgG4 serum levels and pancreatic tissue with respect to the simultaneous presence of autoimmune pancreatitis in patients with pancreatic cancer. Methods: IgG4 serum levels were examined In 106 patients with histologically confirmed pancreatic cancer. The level of 135 mg/dl was considered as the normal value. Pancreatic tissue was histologically examined with respect to the presence of markers of autoimmune pancreatitis. Results: A higher IgG4 level than the cut-off value of 135 mg/dl was proven in 11 patients with pancreatic cancer. Of these 11 patients, 7 had levels twice the normal limit (65.6%). Autoimmune pancreatitis was diagnosed in these individuals. In the case of 1 patient, it was basically an unexpected finding; another patient was initially diagnosed with autoimmune pancreatitis. Repeated biopsy of the pancreas at the time of diagnosis did not confirm the presence of tumour structures, therefore steroid therapy was started. At a check-up 6 months after starting steroid therapy, the condition of the patient improved subjectively and IgG4 levels decreased. However, endosonographically, malignancy was suspected, which was subsequently confirmed histologically. This patient also demonstrated an IgG4 level twice the normal limit. Conclusion: IgG4-related diseases can be accompanied by the simultaneous occurrence of malignancies, which also applies to autoimmune pancreatitis. Chronic pancreatitis is considered a risk factor for pancreatic cancer. It cannot be reliably confirmed whether this also applies to autoimmune pancreatitis. In accordance with other works, however, it is evident that, despite the described high sensitivity and specificity for IgG4 elevation in the case of autoimmune pancreatitis, even levels twice the normal limit are demonstrable in some individuals with pancreatic cancer, without the presence of autoimmune pancreatitis. We believe that patients with IgG4-related disease, including autoimmune pancreatitis, must be systematically monitored with respect to the potential presence of malignancy.

scholarly journals Normal FGF-21-Serum Levels in Patients with Carnitine Palmitoyltransferase II (CPT II) Deficiency

2019 ◽  
Vol 20 (6) ◽  
pp. 1400 ◽  
Author(s):  
Leila Motlagh Scholle ◽  
Diana Lehmann ◽  
Pushpa Joshi ◽  
Stephan Zierz
Keyword(s):  
Citrate Synthase ◽  
Serum Levels ◽  
Carnitine Palmitoyltransferase ◽  
Fibroblast Growth Factor 21 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Mitochondrial Fatty Acid ◽  
Significant Difference ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency

Fibroblast growth factor 21 (FGF-21) is known to be a biomarker for mitochondrial disorders. An upregulation of FGF-21 in serum and muscle of carnitine palmitoyltransferase I (CPT I) and carnitine palmitoyltransferase II (CPT II) knock-out mice has been reported. In human CPT II deficiency, enzyme activity and protein content are normal, but the enzyme is abnormally regulated by malonyl-CoA and is abnormally thermolabile. Citrate synthase (CS) activity is increased in patients with CPT II deficiency. This may indicate a compensatory response to an impaired function of CPT II. In this study, FGF-21 serum levels in patients with CPT II deficiency during attack free intervals and in healthy controls were measured by enzyme linked immunosorbent assay (ELISA). The data showed no significant difference between FGF-21 concentration in the serum of patients with CPT II deficiency and that in the healthy controls. The results of the present work support the hypothesis that in muscle CPT II deficiency, in contrast to the mouse knockout model, mitochondrial fatty acid utilization is not persistently reduced. Thus, FGF-21 does not seem to be a useful biomarker in the diagnosis of CPT II deficiency.

scholarly journals An Overlapping Case of IgG4-Related Disease and Systemic Lupus Erythematosus

2019 ◽  
Vol 7 ◽  
pp. 232470961986229 ◽  
Author(s):  
Srikanth Naramala ◽  
Sharmi Biswas ◽  
Sreedhar Adapa ◽  
Vijay Gayam ◽  
Venu Madhav Konala ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Disease ◽  
Lymph Node Biopsy ◽  
Systemic Lupus ◽  
Immunoglobulin G4 ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Double Stranded Dna ◽  
Serum Igg4

We are reporting a case of a 63-year-old Chinese female who presented to the rheumatology clinic with positive antinuclear antibody and unintentional weight loss along with lymphadenopathy. Further workup revealed eosinophilia, elevated anti–double stranded DNA, serum protein, and serum IgG4 (immunoglobulin G4). The patient was diagnosed with systemic lupus erythematosus. Due to the raised IgG4 level along with eosinophilia and diffuse lymphadenopathy, IgG4-related systemic disease was suspected. It was confirmed with IgG4 staining on lymph node biopsy. Our case is presenting the fact that systemic lupus erythematosus and IgG4-related disease can be present in the same patient with multiple overlapping features making accurate diagnosis challenging.

scholarly journals Gastric calcifying fibrous tumor suspected to be complicated with immunoglobulin G4-related disease treated by laparoscopy and endoscopy cooperative surgery: a case report

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Ryoga Hamura ◽  
Tomoki Koyama ◽  
Masahiko Kawamura ◽  
Takeshi Kawamura ◽  
Mayo Nakamura ◽  
...  
Keyword(s):  
Submucosal Tumor ◽  
Wedge Resection ◽  
Pathological Examination ◽  
Upper Gastrointestinal Endoscopy ◽  
Immunoglobulin G4 ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Serum Igg4 ◽  
Calcifying Fibrous Tumor ◽  
Fibrous Tumor

Abstract Background Calcifying fibrous tumor (CFT) is a rare benign soft tissue lesion. Case presentation A 30-year-old woman was admitted to our hospital with complaints of epigastralgia. A 15-mm submucosal tumor was identified in the greater curvature of the superior body of the stomach by upper gastrointestinal endoscopy. Endoscopic ultrasonography revealed a hypoechoic lesion with an acoustic shadow consistent with calcification. Computed tomography showed a gastric tumor with calcification. A gastrointestinal stromal tumor was diagnosed, and gastric wedge resection was performed by laparoscopy and endoscopy cooperative surgery. On pathological examination, the tumor was identified to be a CFT. Postoperative serum IgG4 levels were 26.0 mg/dl, which supported the diagnosis of probable immunoglobulin G (IgG) 4-related disease, according to the comprehensive diagnostic criteria of IgG4-related disease. The patient was discharged on postoperative day 7 and remains well with no evidence of tumor recurrence for 2 years after resection. Conclusion We herein reported a patient with a gastric CFT suspected to be complicated with immunoglobulin G4-related disease that was successfully treated by laparoscopy and endoscopy cooperative surgery.

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