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)
Citations
More filters
••
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.
2 citations
••
18 Nov 2016References
More filters
••
TL;DR: The enhanced liver fibrosis (ELF) score may be a clinically useful indicator of active fibrosis and the extent of disease in IgG4-RD, and b-cell depletion has the potential to halt continued collagen deposition by attenuating the secretory phenotype of myofibroblasts in Igg4- RD lesions.
Abstract: Objectives Fibrosis is a predominant feature of IgG4-related disease (IgG4-RD). B-cell depletion induces a prompt clinical and immunological response in patients with IgG4-RD, but the effects of this intervention on fibrosis in IgG4-RD are unknown. We used the enhanced liver fibrosis (ELF) score to address the impact of rituximab on fibroblast activation. The ELF score is an algorithm based on serum concentrations of procollagen-III aminoterminal propeptide, tissue inhibitor of matrix metalloproteinase-1 and hyaluronic acid. Methods Ten patients with active, untreated IgG4-RD were enrolled. ELF scores were measured and correlated with the IgG4-RD Responder Index, serum IgG4, circulating plasmablasts and imaging studies. Through immunohistochemical stains for CD3, CD20, IgG4 and α-smooth muscle actin, we assessed the extent of the lymphoplasmacytic infiltration and the degree of fibroblast activation in one patient with tissue biopsies before and after rituximab. Results The ELF score was increased in patients with IgG4-RD compared with healthy controls (8.3±1.4 vs 6.2±0.9; p=0.002) and correlated with the number of organs involved (R 2 =0.41; p=0.04). Rituximab induced significant reductions in the ELF score, the number of circulating plasmablasts and the IgG4-RD Responder Index (p Conclusions The ELF score may be a clinically useful indicator of active fibrosis and the extent of disease in IgG4-RD. B-cell depletion has the potential to halt continued collagen deposition by attenuating the secretory phenotype of myofibroblasts in IgG4-RD lesions.
101 citations
Additional excerpts
...[79]....
[...]
••
Yui Shimizu1, Motohisa Yamamoto1, Yasuyoshi Naishiro1, Gohta Sudoh1, Keisuke Ishigami1, Hidetaka Yajima1, Tetsuya Tabeya1, Mikiko Matsui1, Chisako Suzuki1, Hiroki Takahashi1, Nobuhiko Seki1, Tetsuo Himi1, Ken Yamashita1, Hiroko Noguchi1, Tadashi Hasegawa1, Yasuo Suzuki1, Saho Honda1, Takashi Abe1, Kohzoh Imai1, Yasuhisa Shinomura1 •
TL;DR: Salivary secretion can be improved even in cases with lower levels of salivary gland secretion before treatment in IgG4-RD, but improvements in the amount of salIVary secretion decrease with histological changes with delayed therapeutic intervention, suggesting that early intervention is needed to improve outcomes in patients with IgG 4-MD.
Abstract: Objective. Despite ongoing research, the clinical and histopathological natural history of immunoglobulin (Ig) G4-related disease (IgG4-RD) remains unclear and the optimal time to initiate treatment is unknown. A focus on clinical symptoms rather than image finding is recommended for therapeutic initiation in autoimmune pancreatitis, but evidence for this approach is lacking. We aimed to retrospectively analyse disease duration, efficacy of treatment with glucocorticoids and results of histopathological examination of submandibular gland specimens to clarify the necessity for early intervention in IgG4-RD. Methods. Salivary secretions were assessed before and after treatment in 26 cases of IgG4-related Mikulicz’s disease (IgG4-MD). Relationships between disease duration, amount of salivary secretion before treatment, improvement of salivary secretion and ratios of areas of residual acini, fibrosis and lymphoid follicles in the involved submandibular gland specimens were analysed. Results. Salivary secretions were significantly reduced in cases with illness of >2 years (P < 0.05). An inverse correlation was seen between improved amount of salivary secretion and amount of salivary secretion before treatment (r =0.60). Improved amount of salivary secretion was also associated with each histological factor (acini, r = 0.29; fibrosis, r =0.23; lymphoid follicles, r =0.31), which showed interrelationships (acini and lymphoid follicles, r =0.23; acini and fibrosis, r = 0.42; lymphoid follicles and fibrosis, r = 0.30). Conclusion. Salivary secretion can be improved even in cases with lower levels of salivary secretion before treatment in IgG4-RD, but improvements in the amount of salivary secretion decrease with histological changes with delayed therapeutic intervention. These data suggest that early intervention is needed to improve outcomes in patients with IgG4-MD.
100 citations
Additional excerpts
...제1형 자가면역췌장염과 IgG4 연관 타액선염은 후복막 섬유증, 경화장간막염(sclerosing mesenteritis), 섬유화종격동염(fibrosing mediastinitis)에 비해 스테로이드에 대한 반응이 좋다[78]....
[...]
••
TL;DR: IgG 4-related sialadenitis belongs to the IgG4-related systemic disease spectrum and shows a swift response to immunosuppression.
Abstract: Purpose of reviewAn enlarged salivary gland or lacrimal gland raises a wide differential diagnosis that includes both benign inflammatory conditions and malignant disorders. This review aims to address the numerous controversies that have arisen regarding inflammatory diseases of the salivary gland
94 citations
Additional excerpts
...IgG4 연관된 침샘염은 림프종과의 감별이 필요하다[42]....
[...]
••
TL;DR: It is suggested that innate immune responses mediated through TLRs may play a role in the development of IgG4-related disease, in part by production of BAFF from basophils.
Abstract: IgG4-related disease (IRD) is characterized by systemic IgG4 antibody responses and by infiltration of IgG4-expressing plasma cells into the affected organs. Although T helper type 2 (Th2) cytokines are implicated in enhanced IgG4 responses, molecular mechanisms accounting for the development of IgG4 antibody responses are poorly defined. Since basophils function as antigen-presenting cells for Th2 responses, we tried to clarify the role of basophils in the development of IgG4 responses in this study. IgG4 and cytokine responses to various nucleotide-binding oligomerization domain-like receptor and Toll-like receptor (TLR) ligands were examined by using basophils isolated from healthy controls and from patients with IgG4-related disease. Activation of TLRs in basophils from healthy controls induced IgG4 production by B cells, which effect was associated with enhanced production of B cell activating factor (BAFF) and IL-13. In addition, activation of TLRs in basophils from patients with IRD induced a large amount of IgG4 by B cells from healthy controls. This enhancement of IgG4 production was again associated with BAFF and IL-13. These data suggest that innate immune responses mediated through TLRs may play a role in the development of IgG4-related disease, in part by production of BAFF from basophils.
93 citations
Additional excerpts
...또한 IgG4 연관 질환 환자의 호염구는 정상인에 비 해 호염구 toll-유사 수용체 자극에 의해 좀 더 많은 양의 IgG4를 만든다[20]....
[...]
••
TL;DR: It is concluded that patients with elevated serum IgG4 levels encountered in clinical practice manifest a wide array of disorders, and only a small minority of them has IgG 4-RD.
Abstract: IgG4-related disease (IgG4-RD) is a recently described systemic fibroinflammatory disease associated with elevated circulating levels of IgG4 and manifests a wide spectrum of clinical presentations. Although serum IgG4 level has been described to be the most sensitive and specific laboratory test for the diagnosis of IgG4-RD, it is recognized that an elevated serum IgG4 level can be encountered in other diseases. In this study, we sought to identify the frequency of IgG4-RD and other disease associations in patients with elevated serum IgG4 levels seen in clinical practice. Among 3,300 patients who underwent IgG subclass testing over a 2-year period from January 2009 to December 2010, 158 (4.8%) had an elevated serum IgG4 level (>140 mg/dL). IgG4 subclass testing was performed for evaluation of suspected IgG4-RD or immunodeficiency. Twenty-nine patients (18.4%) had definite or possible IgG4-RD. Among those patients without IgG4-RD, a broad spectrum of biliary tract, pancreatic, liver, and lung diseases, as well as systemic vasculitis, was diagnosed. We conclude that patients with elevated serum IgG4 levels encountered in clinical practice manifest a wide array of disorders, and only a small minority of them has IgG4-RD.
92 citations
Additional excerpts
...혈청 IgG4 상승은 정상인의 약 5%와 췌장암, 양성 췌장 종양, 췌장염, 아토피 피부염, 보 통천포창, 항호중구세포질항체 연관 전신 혈관염, 저보체 혈증 두드러기 혈관염(hypocomplementemic vasculitis) 등에서도 혈청 IgG4 상승이 보고된 바 있다[74]....
[...]