Immunoglobulin G4-Related Disease
01 Aug 2015-Journal of Reproduction and Development (Korean College of Rheumatology)-Vol. 22, Iss: 4, pp 213-222
TL;DR: Rituximab is reported to be an effective therapy for treatment of IgG4-RD, even without concomitant glucocorticoid therapy, which is the first-line therapy for patients with multiple organ dysfunction and clinical symptoms.
Abstract: Immunoglobulin G4-related disease (IgG4-RD) is an emerging immune-mediated fibro-inflammatory disorder which can involve any organ. The main characteristics of IgG4-RD are increased serum IgG4 concentration, abundant IgG4+ plasma cells in affected tissues, and painless swollen organs often without general symptoms. Typical pathology features of IgG4-RD are lymphoplasmacytic infiltration, dense storiform fibrosis, and obliterative pheblitis. The pathogenesis of IgG4-RD remains elusive, but involvement of excess production of type 2 T helper cells, regulatory T-cell cytokines, and B-cell activating factor in the development of IgG4-RD has been suggested. Diagnosis of IgG4-RD can be made on the basis of serological, imaging, particularly histopathological findings. Glucocorticoid is the first-line therapy for patients with multiple organ dysfunction and clinical symptoms. Drugs such as azathioprine, mycophenolate mofetil, methotrexate, and cyclophosphamide can be used as steroid-sparing agents. Rituximab is reported to be an effective therapy for treatment of IgG4-RD, even without concomitant glucocorticoid therapy. This review summarizes current concepts on pathophysiology, clinical manifestations, and treatment of IgG4-RD. (J Rheum Dis 2015;22:213-222)
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TL;DR: Using alternative preoperative diagnostic methods such as endoscopic ultrasound-guided fine-needle biopsy or the biopsy unroofing technique could spare the patient from unnecessary surgical treatment.
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18 Nov 2016References
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TL;DR: The data support the concept that type 2 AIP cases were less likely to be associated with a history of alcohol abuse, and showed significantly more foci of periductal inflammation and neutrophilic microabscesses, and advocate the position that all subsequent studies attempt to substratify patients into these 2 groups.
Abstract: Autoimmune pancreatitis (AIP) is a chronic inflammatory disease of the pancreas. Examination of pancreatic resection specimens from patients with AIP has shown that there are 2 subclasses of this disease. However, there is no widely accepted pathologic classification scheme and the clinical significance of such a classification remains to be established. In this study, we revisited the subclassification of AIP and examine whether this provides clinically and prognostically meaningful information. We evaluated 29 pancreatic resection specimens from patients with AIP. Demographic, clinical, and imaging data were recorded, as was evidence of extrapancreatic manifestations. In addition to a detailed and semiquantitative histologic evaluation, immunohistochemistry for IgG4 was performed on pancreatic and extrapancreatic tissues. We also evaluated 48 consecutive cases of chronic pancreatitis, not otherwise specified. The resected specimens could readily be subclassified into 2 subtypes: type 1 (n=11) and type 2 (n=18). In comparison with patients with type 2 disease, patients with type 1 disease were significantly more likely to be males (P=0.09), older (P=0.02), and present with jaundice (P=0.01), and less likely to be associated with abdominal pain (P=0.04). On imaging, the pancreatic tail cut-off sign was exclusively seen in patients with type 2 disease (4 of 10 cases). Hypercellular inflamed interlobular stroma was unique to type 1 pattern (91%), whereas significant ductal injury in the form of microabscesses and ductal ulceration was almost exclusively seen in type 2 pattern (78%). Eight of 10 patients with a type 1 pattern had evidence of a systemic disease. Three patients with type 2 disease had recurrent episodes of pancreatitis after their pancreatic resection. In comparison with the cohort of chronic pancreatitis, not otherwise specified, type 2 AIP cases were less likely to be associated with a history of alcohol abuse, and showed significantly more foci of periductal inflammation and neutrophilic microabscesses. Our review of pancreatic resection specimens shows 2 histologically distinct forms of AIP. Our data support the concept that type 1 AIP is a systemic disease and is the pancreatic manifestation of IgG4-related systemic disease. Type 2 disease is confined to the pancreas. The intensity of the periductal inflammatory infiltrate and the presence of ductal neutrophilic abscesses are features that assist in distinguishing type 2 AIP from chronic pancreatitis, not otherwise specified. Although imperfect, clinical and imaging features may help distinguish the 2 subtypes of AIP. On the basis of these significant differences between the 2 types of AIP, we advocate the position that all subsequent studies attempt to substratify their patients into these 2 groups.
165 citations
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...자가 면역췌장염은 제1형과 제2형으로 분류되는데 제1형 자가 면역췌장염은 IgG4와 연관된 질병으로 림프형질세포가 주로 침윤되나 제2형 자가면역췌장염에서는 중성구가 췌 도상피세포 쪽으로 침윤된다[33]....
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TL;DR: To elucidate the pathologic role of follicular helper T (Tfh) cells and their subsets in active, untreated IgG4‐related disease, and to investigate the role of Tfh cells in infectious disease.
Abstract: Objective
To elucidate the pathologic role of follicular helper T (Tfh) cells and their subsets in active, untreated IgG4-related disease.
Methods
Fifteen patients with active, untreated, biopsy-proven IgG4-related disease, 24 patients with primary Sjogren's syndrome (SS), 12 patients with allergic rhinitis, and 23 healthy controls were evaluated. Tfh cells were defined as CD3+CD4+CXCR5+CD45RA– cells. Circulating Tfh cell subsets among CXCR5+CD45RA–CD4+ T cells were defined as Tfh17 cells (CXCR3–CCR6+), Tfh1 cells (CXCR3+CCR6–), or Tfh2 cells (CXCR3–CCR6–). CD19+CD20–CD27+CD38+ cells were defined as plasmablasts. Serum cytokine levels (interleukin-4 [IL-4], IL-10, IL-21, and IL-33) were measured by cytometric bead array or enzyme-linked immunosorbent assay.
Results
Patients with IgG4-related disease had significantly increased levels of Tfh2 cells compared to healthy controls or patients with primary SS or allergic rhinitis. Increased Tfh2 levels were strongly associated with increased serum IgG4 levels and the IgG4:IgG ratio in IgG4-related disease. A positive correlation was observed between Tfh2 counts, plasmablast counts, and serum IL-4 levels. Interestingly, levels of plasmablasts and serum IL-4 and IgG4 decreased after treatment with glucocorticoids, whereas no obvious change was observed in Tfh2 cell counts.
Conclusion
The Tfh2 cell count was specifically increased in IgG4-related disease and was correlated with elevated serum levels of IgG4 and IL-4 and plasmablast counts. Tfh2 cells were the only component that was not affected by glucocorticoid treatment, suggesting that Tfh2 cells are the cell type implicated in IgG4-related disease.
160 citations
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TL;DR: Data published to date suggest that ISD may account for a portion of various fibroinflammatory conditions of unknown cause encountered in the chest, including inflammatory pseudotumours, idiopathic interstitial pneumonias, fibrosing mediastinitis, inflammatory pleural lesions and, occasionally, airway disease.
Abstract: Immunoglobulin (Ig)G4-related sclerosing disease (ISD) (also called IgG4-related systemic disease, IgG4-related disease or hyper-IgG4 disease) is a recently described systemic fibroinflammatory disease associated with elevated circulating levels of IgG4. Although initial descriptions of this disorder focused on its pancreatic presentation (autoimmune pancreatitis), it has become apparent that ISD is a systemic disease with many facets. The lesion of ISD is characterised by lymphoplasmacytic inflammation, fibrosis, phlebitis and increased numbers of IgG4-positive plasma cells. The disease can either be localised to one or two organs, or be present with diffuse multi-organ disease. Furthermore, lesions in different organs can present simultaneously or metachronously. In the thorax, lesions associated with ISD have been described in the lung parenchyma, airways and pleura, as well as the mediastinum. Data published to date suggest that ISD may account for a portion of various fibroinflammatory conditions of unknown cause encountered in the chest, including inflammatory pseudotumours, idiopathic interstitial pneumonias, fibrosing mediastinitis, inflammatory pleural lesions and, occasionally, airway disease. Some aspects of pulmonary manifestations attributed to ISD remain controversial and additional studies are needed to clarify the relationship along with the increasing relevance of this disorder to pulmonary medicine.
156 citations
Additional excerpts
...특이적 간질성 폐렴과의 감별진단이 필요하다[59]....
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TL;DR: Elevated IgG 4/total IgG ratios in tissue biopsies are more useful than the number of IgG4+ plasma cells per high-power field in cases of RPF that are highly fibrotic.
154 citations
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TL;DR: The results of this short-term study demonstrate that LSP-based allergen immunotherapy was safe and able to induce T(H)1-type immune deviation,allergen-specific IL-10 production, and T-cell hyporesponsiveness.
Abstract: Background: There is a need to improve the safety and efficacy of allergen-specific immunotherapy. Long synthetic peptide-based immunotherapy was proven safe, immunogenic, and protective in preclinical trials. Objective: To evaluate the safety and immunogenicity of an allergen-derived long synthetic overlapping peptide (LSP) immunotherapy, we designed a double-blind, placebo-controlled phase I clinical trial in patients hypersensitive to bee venom. Methods: Patients from the active group were injected at day 0 with a mixture of 3 LSPs mapping the entire PLA2 molecule, a major bee venom allergen, in a dose-escalating protocol to a maintenance dose of 100 μg per peptide repeated at days 4, 7, 14, 42, and 70. The control group was injected with human albumin. Results: Whereas specific T-cell proliferation in the peptide group increased up to day 14, a sharp decline was observed thereafter, ending in specific T-cell hyporesponsiveness at day 80. Serum-specific IgG4 response was enhanced, in contrast to anti-PLA2 IgE. Specific T-cell cytokine modulation was marked by increased IL-10 and IFN-γ secretion. LSP injections were well tolerated in all patients except for mild, late allergic reactions in 2 patients at day 70. Conclusions: The results of this short-term study demonstrate that LSP-based allergen immunotherapy was safe and able to induce T H 1-type immune deviation, allergen-specific IL-10 production, and T-cell hyporesponsiveness. LSPs, which offer the advantage of covering all possible T-cell epitopes for any HLA genotype, can be considered candidates for a novel and safe approach of specific immunotherapy. (J Allergy Clin Immunol 2003;111:854-61.)
149 citations
Additional excerpts
...이러한 주장은 IgG4가 관용 유도를 통한 알러지 질환 치료를 한 경우에 생성되고 IgG4가 차단 항체로 작용하여 비만 세포 표면에 있는 IgE에 항원이 붙는 것을 억제함으로써 알러지 질병 발생을 억제할 수 있다는 연구 결과를 뒷받침해 준다[22]....
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...CD40과는 달리, IgG4 연관 질환에서 B 세 포의 CD80과 CD86의 발현은 일차성 쇼그렌증후군 또는 정상인에 비해 증가되어 있는데 이는 CD23/CD21 상호 작용을 촉진하여 IgG4와 IgE 생성을 증가시키는데 관여할 것으로 예상된다[12]....
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