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.
Abstract: Introduction Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder characterized by specific pathologic findings and often, but not in all cases, elevated serum IgG4 concentration. Although it can virtually involve every organ system, cases involving the gastrointestinal tract and especially gastric mass lesions have rarely been reported. Patient concerns A 45-year-old man, who was incidentally discovered asymptomatic subepithelial tumor (SET), by endoscopy, on the greater curvature of the upper gastric body, was referred to our hospital for further evaluation. Diagnosis The patient was postoperatively diagnosed with IgG4-RD by histopathologic results. Interventions The patient underwent laparoscopic wedge resection. Outcomes The patient is presently followed up annually in our clinic and had no problems and showed no signs of recurrence in examination. Conclusion We reported a rare case of IgG4-RD presenting as a gastric SET. The first line treatment of IgG4-RD is glucocorticoid administration. However, because pathologic examination is challenging owing to the lesion location, preoperative diagnosis is difficult and may lead to unnecessary gastric resection. Thus, 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.
2 citations
18 Nov 2016
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TL;DR: The evidence in favour of alternative macrophage activation by the TH2-type cytokines interleukin-4 (IL-4) and IL-13 is assessed, and its limits and relevance to a range of immune and inflammatory conditions are defined.
Abstract: The classical pathway of interferon-gamma-dependent activation of macrophages by T helper 1 (T(H)1)-type responses is a well-established feature of cellular immunity to infection with intracellular pathogens, such as Mycobacterium tuberculosis and HIV. The concept of an alternative pathway of macrophage activation by the T(H)2-type cytokines interleukin-4 (IL-4) and IL-13 has gained credence in the past decade, to account for a distinctive macrophage phenotype that is consistent with a different role in humoral immunity and repair. In this review, I assess the evidence in favour of alternative macrophage activation in the light of macrophage heterogeneity, and define its limits and relevance to a range of immune and inflammatory conditions.
5,930 citations
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...Furukawa 등[16]은 MIkulicz 병 환자의 턱밑 타액선의 M2 대식세포수가 일차성 쇼그 렌증후군 환자 및 정상인에 비해 증가되어있고 섬유화 정 도와 비례하며 IL-10과 CCL18이 M2 대식세포와 같은 위 치에서 관찰된다고 보고하였다....
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...대식세포는 Th1 반응에 의해 유도되는 전통적 대식세포 인 M1 대식세포와 Th2 반응에 의해서 분비되는 IL-4, IL-10 또는 조절 T 세포로부터 만들어지는 IL-10에 의해 유도되는 M2 대식세포로 분류된다[15]....
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...M2 대식세포는 Th2 면역반응을 증강시키고 IL-10, IL-13, Chemokine (C-C motif) ligand 18 (CCL18)과 같은 섬유화를 촉진시키 는 사이토카인을 분비한다[15]....
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TL;DR: Patients with sclerosing pancreatitis have high serum IgG4 concentrations, providing a useful means of distinguishing this disorder from other diseases of the pancreas or biliary tract.
Abstract: Background Sclerosing pancreatitis is a unique form of pancreatitis that is characterized by irregular narrowing of the main pancreatic duct, lymphoplasmacytic inflammation of the pancreas, and hypergammaglobulinemia and that responds to glucocorticoid treatment. Preliminary studies suggested that serum IgG4 concentrations are elevated in this disease but not in other diseases of the pancreas or biliary tract. Methods We measured serum IgG4 concentrations using single radial immunodiffusion and an enzyme-linked immunosorbent assay in 20 patients with sclerosing pancreatitis, 20 age- and sex-matched normal subjects, and 154 patients with pancreatic cancer, ordinary chronic pancreatitis, primary biliary cirrhosis, primary sclerosing cholangitis, or Sjogren's syndrome. Serum concentrations of immune complexes and the IgG4 subclass of immune complexes were determined by means of an enzyme-linked immunosorbent assay with monoclonal rheumatoid factor. Results The median serum IgG4 concentration in the patients ...
2,355 citations
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...IgG4 연관 질환은 비교적 최근에 알려진 질환으로 2001년 Hamano 등[2]은 자가면역췌장염 환자 혈청에서 IgG4가 상승되어 있으며 IgG4 양성 형질세포가 많이 침윤 되었음을 관찰하고 경화성 췌장염으로 보고하였고, 2003 년 Kamisawa 등[3]은 이 질환을 IgG4 연관 자가면역질환 으로 명명하였다....
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...대부분의 제1 형 자가면역췌장염 환자에서 IgG4가 증가하며 질병 활성 도와 관련이 있지만 제2형 자가면역췌장염에서는 IgG4의 상승이 흔하지 않다[2]....
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Vikram Deshpande1, Yoh Zen2, John Kc Chan, Eunhee E Yi3, Yasuharu Sato4, Tadashi Yoshino4, Günter Klöppel5, J. Godfrey Heathcote6, Arezou Khosroshahi1, Judith A. Ferry1, Rob C. Aalberse7, Daniel Bloch1, William R. Brugge1, Adrian C Bateman8, Mollie N. Carruthers1, Suresh T. Chari3, Wah Cheuk, Lynn D. Cornell3, Carlos Fernandez-del Castillo1, David G. Forcione1, Daniel L. Hamilos1, Terumi Kamisawa9, Satomi Kasashima, Shigeyuki Kawa10, Mitsuhiro Kawano11, Gregory Y. Lauwers1, Yasufumi Masaki12, Yasuni Nakanuma11, Kenji Notohara, Kazuichi Okazaki13, Ji Kon Ryu14, Takako Saeki, Dushyant V. Sahani1, Thomas C. Smyrk3, James Robert Stone1, Masayuki Takahira11, George Webster15, Motohisa Yamamoto16, Giuseppe Zamboni17, Hisanori Umehara12, John H. Stone1 •
Harvard University1, University of Cambridge2, Mayo Clinic3, Okayama University4, Technische Universität München5, Dalhousie University6, University of Amsterdam7, Southampton General Hospital8, Tokyo Metropolitan Komagome Hospital9, Shinshu University10, Kanazawa University11, Kanazawa Medical University12, Kansai Medical University13, Seoul National University14, University College London15, Sapporo Medical University16, University of Verona17
TL;DR: This statement proposes a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy, and advocates the use of strict criteria for accepting newly proposed entities or sites as components of the IgG 4- related disease spectrum.
Abstract: IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and-often but not always-elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4-7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4⁺ plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum.
2,041 citations
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...이외에 배중심(germinal center), 림프여포(lymphoid follicle), 비폐쇄성 정맥염, 폐쇄성 동맥염 등의 소견이 관찰 되기도 한다[30]....
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...조직병리 소견 IgG4 연관 질환의 중요한 조직병리 소견으로는 림프형질 세포 침윤, 많은 수의 IgG4 양성 형질세포 침윤, 나선형 섬유화(storiform fibrosis), 폐쇄성 정맥염(obliterativepheblitis,), 경도 또는 중증도의 호산구 침윤 등이다[30]....
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...서 IgG4+ 형질세포 관찰만으로 IgG4 연관 질환을 진단할 수 없다[30]....
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1,948 citations
TL;DR: In this article, the immunological mechanisms that initiate, sustain and suppress the fibrotic process were studied. But the mechanisms that are involved in fibrogenesis are now known to be distinct from those involved in inflammation.
Abstract: Tissue fibrosis (scarring) is a leading cause of morbidity and mortality. Current treatments for fibrotic disorders, such as idiopathic pulmonary fibrosis, hepatic fibrosis and systemic sclerosis, target the inflammatory cascade, but they have been widely unsuccessful, largely because the mechanisms that are involved in fibrogenesis are now known to be distinct from those involved in inflammation. Several experimental models have recently been developed to dissect the molecular mechanisms of wound healing and fibrosis. It is hoped that by better understanding the immunological mechanisms that initiate, sustain and suppress the fibrotic process, we will achieve the elusive goal of targeted and effective therapeutics for fibroproliferative diseases.
1,466 citations