Renal lesions in IgG4-related systemic disease.

Department of Internal Medicine, Nagaoka Red Cross Hospital.
Internal Medicine (Impact Factor: 0.9). 02/2007; 46(17):1365-71.
Source: PubMed


Recently, a new concept of IgG4-related systemic disease including autoimmune pancreatitis, characterized by a high serum IgG4 level and tissue infiltration by IgG4-positive plasma cells, has been proposed. Our aim was to investigate the renal involvement in this condition.
We investigated the results of laboratory and imaging studies of the kidneys in 7 patients with IgG4-related systemic disease, and examined the renal histology in four of them. All patients showed elevated serum IgG4 levels, and 4 had autoimmune pancreatitis. The other three patients showed involvement of various extrapancreatic organs (lymphadenopathy, sialadenitis or renal insufficiency), and abundant IgG4-positive plasma cell infiltration was confirmed in their affected tissues.
Six of the 7 patients showed some renal abnormalities. In one patient, hydronephrosis was observed accompanied by retroperitoneal fibrosis. Another patient showed multiple low-density areas in both kidneys by computed tomography, and gallium citrate scintigraphy showed gallium-67 accumulation in both kidneys, although renal function was normal. Four patients had tubulointerstitial nephritis. In two of them, the tubulointerstitial nephritis was diffuse. In one patient, marked diffuse but patchily distributed lymphoplasmacytic infiltration of the renal interstitium was observed. In another patient, computed tomography showed a tumor-like low-density mass; open biopsy of the mass showed aggregates of lymphocytes and plasma cells in the renal interstitium.
Renal parenchymal lesions in IgG4-related systemic disease are due to dense lymphoplasmacytic infiltration of the renal interstitium, and the lesions vary from diffuse tubulointerstitial nephritis to tumor-like masses according to the distribution patterns of the infiltrating cells.

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    • "This condition can be confirmed by elevated serum IgG4 levels and prominent IgG4-positive plasmacyte infiltration of involved organs. IgG4-RD may be present in a wide variety of conditions, such as Mikulicz's disease (MD), autoimmune pancreatitis (AIP), hypophysitis, Riedel thyroiditis, interstitial pneumonitis, interstitial nephritis, lymphadenopathy, retroperitoneal fibrosis, and inflammatory pseudotumor [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]. 18 F-fluorodeoxyglucose positron emission tomography/ computed tomography (FDG-PET/CT) has been established as a modality for diagnosing and staging several types of malignancies [15]. "
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    ABSTRACT: Objectives This study aimed to evaluate the utility of imaging techniques, including 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), in immunoglobulin (IgG)4-related disease (IgG4-RD). Methods We reviewed eight IgG4-RD patients who were referred to our hospital between August 2006 and April 2012. All cases underwent FDG-PET/CT and brain magnetic resonance imaging (MRI) and endobronchial ultrasonography (EBUS) were also performed in five cases and one case, respectively. Results Although nearly all patients with IgG4-RD in this study were negative for CRP (mean 0.22 mg/dL), various organ involvement sites were detected by FDG-PET/CT. In the active phase in two autoimmune pancreatitis (AIP) cases, FDG-PET/CT showed longitudinal and heterogeneous FDG accumulation in the pancreas with FDG uptake in the hilar or mediastinal lymph nodes. Follow-up FDG-PET/CT after therapy in one case revealed that the abnormal FDG uptake in all affected lesions had completely disappeared. In two cases, brain MRI revealed asymptomatic hypertrophic pachymeningitis. In one case, EBUS imaging of mediastinal lymph node swelling was consistent with tortuous vessels with high Doppler signals and hyperechoic strands between lymph nodes. Conclusions When FDG-PET/CT shows FDG accumulation, characteristic of IgG4-RD in organs, without evidence of an associated inflammatory reaction, a diagnosis of IgG4-RD can be made. Treatment effects can be assessed by the disappearance of FDG uptake. A routine brain MRI is useful for detecting asymptomatic hypertrophic pachymeningitis. EBUS may also be useful for differentiating among the etiologies of lymphadenopathy with characteristic sonographic imaging findings.
    Joint, bone, spine: revue du rhumatisme 07/2014; 81(4). DOI:10.1016/j.jbspin.2014.01.010 · 2.90 Impact Factor
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    • "IgG4 electron-dense deposits have been demonstrated in the peritubular basement membrane using electron microscopy. The renal glomeruli are usually uninvolved but few cases with concurrent membranous nephropathy have been recorded.144-148 The tubulointerstitial nephritis is steroid responsive, whereas the response of membranous glomerulonephritis can be variable. "
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    ABSTRACT: Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies.
    Yonsei medical journal 01/2012; 53(1):15-34. DOI:10.3349/ymj.2012.53.1.15 · 1.29 Impact Factor
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    • "Lymphadenopathy is a common complication (40–50%) and hypocomplementemia is observed in 30–40% of cases [3, 4, 5, 6, 7, 8]. In IgG4-related nephropathy, the lesions are mainly located at the tubulointerstitium rather than at glomeruli [9, 10, 11, 12]. Massive infiltration of IgG4-positive plasma cells and serious fibrosis in the interstitium are distinctive findings rather than typical interstitial nephritis. "
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    ABSTRACT: A 59-year-old man was diagnosed with IgG4-related tubulointerstitial nephritis. His symptoms as well as laboratory and imaging findings were improved after initiation of steroid therapy. Serologically, he showed hypocomplementemia (C3 23 mg/dl, C4 <2 mg/dl, CH50 <7 U/ml) with high levels of IgG (IgG4 1,970 mg/dl) and immune complexes (C1q assay 8.1 μg/ml) and a low level of C1q (<2.0 mg/dl). Histologically, he also showed linear depositions of IgG, IgM, C3, C4d, C1q, membrane attack complex and all IgG subclasses (IgG1, IgG2, IgG3 and IgG4) along the tubular basement membrane, as well as granular depositions of these components in the renal interstitium. However, mannose-binding lectin and L-ficolin were not detected in these tissues. Homogeneous electron-dense deposits were observed by electron microscopy in the tubular basement membrane. It appears that the immune complexes might activate the classical pathway of the complement in both blood and local tissues in a patient with IgG4-related tubulointerstitial nephritis.
    07/2011; 1(1):7-14. DOI:10.1159/000330664
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