Cryoglobulinemic glomerulonephritis — lessons from animal models

Kowalewska, Jolanta

doi:10.5603/fhc.2011.0077

Cited by 9 publications

(5 citation statements)

References 68 publications

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“…A large influx of macrophages is a feature of human cryoglobulinemic MPGN . Cryoglobulinemic MPGN shows staining for IgM and/or IgG with or without light chain restrictions, complement fragment C3 on immunofluorescence microscopy, and electron‐dense deposits on electron microscopy . However, our patient did not have cryoglobulinemia clinically, and typical cryoglobulinemic glomerulonephritis was ruled out because there was no staining for IgM or IgG or electron‐dense deposits.…”

Section: Discussionmentioning

confidence: 65%

“…8 Cryoglobulinemic MPGN shows staining for IgM and/or IgG with or without light chain restrictions, complement fragment C3 on immunofluorescence microscopy, and electron-dense deposits on electron microscopy. 9 However, our patient did not have cryoglobulinemia clinically, and typical cryoglobulinemic glomerulonephritis was ruled out because there was no staining for IgM or IgG or electron-dense deposits. We also considered the possibility of a MIDD-like condition due to the peripheral staining for λ light chains and C3.…”

Section: Pathological Findingsmentioning

confidence: 75%

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A case of endocapillary proliferative glomerulonephritis with macrophages phagocytosing monoclonal immunoglobulin lambda light chain

Watanabe

Osawa

Goto

et al. 2014

Pathology International

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Multiple myeloma (MM) is a plasma-cell neoplasm that can cause renal disorders. Renal lesions in MM can present with a very rare pathological manifestation involving a specific monoclonal immunoglobulin (Ig). We report the case of a 33-year-old woman who had edema, fatigue, elevated serum creatinine levels, hypoalbuminemia, and hypercholesterolemia. She had persistent hematuria and proteinuria lasting 3 years. Serum protein electrophoresis showed an M-spike, and serum immunofixation demonstrated the presence of monoclonal IgG λ. She had proteinuria in the nephrotic range, and a monoclonal λ fragment was present on urine immunofixation. Renal biopsy showed proliferative glomerulonephritis with λ light chain and C3c deposition and inflammatory cell infiltration with CD68. Macrophage lysosomes contained λ light chains, suggesting their partial phagocytosis. She was diagnosed with symptomatic MM and was treated with bortezomib and dexamethasone and an autologous peripheral stem cell transplant conditioned with intravenous melphalan. She achieved a partial response with decreased serum monoclonal protein and improved renal function. This case may be categorized as a monoclonal gammopathy-associated proliferative glomerulonephritis. The biopsy finding of partially phagocytosed Ig λ light chains by macrophages is very rare; this pathological condition is similar to crystal-storing histiocytosis.

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Section: Discussionmentioning

confidence: 65%

Section: Pathological Findingsmentioning

confidence: 75%

A case of endocapillary proliferative glomerulonephritis with macrophages phagocytosing monoclonal immunoglobulin lambda light chain

Watanabe

Osawa

Goto

et al. 2014

Pathology International

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“…Similarly, monocytes accumulating in the glomeruli of patients with MC are not able to process internalised ICs, thus potentially perpetuating glomerular damage [14]. In a murine model of MC-membranoproliferative glomerulonephritis, macrophage depletion protects animals from glomerulonephritis without affecting cryoglobulin removal [15]. This is consonant to the observation that macrophage-driving mesangial expansion and activation are sustained by the release of pro-inflammatory cytokines and pro-cathepsin D from damage-associated molecular patterns-activated macrophages (Table 1) [16].…”

Section: Relevant Pathogenic Aspects Involved In the Choice Of Therapymentioning

confidence: 99%

The challenge of treating hepatitis C virus-associated cryoglobulinemic vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral agents

et al. 2017

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Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered.Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens.The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs.

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“…In lungs, cryglobulin induce proliferation of epithelial tissue as well as cytokine production . Hyper plasia of; epithelial cells, macrophages and mucosal lymphoid cells is consistent with pulmonary local immune reponses [13,15,6].Perivascular cell cuff and aggregation of inflammatory cells suggest subacute to chronic inflammatory reactions involved in delayed type hyper sensitivity in liver [16].Lymphoid cell hypoplasia may be attributed to regulatory T lymphocytes effect in response to the ac-tion of cryglobulin [8].Nephritis and edema in kidneys may be mediated by serum sickness and Arthus reaction [10,9,3].Myocarditis in heart muscle due to inflammatory macrophage activation [9].Thus the immune mediated tissue injuries in mice groups I-III appeared as;type II hypersensitivity in heart muscle ,type III in kidneys and type IV in liver as well as mucosal immune response in lungs. The Conclusions, The human tuberculus cryoglobulin is pathogenic effects for tissue and organs in mice,The pathological effects are immune mediated(cellular immunity),The nature of pathogenic immune mediated was hypersensitivity to some cell body and granuloma formation, Hypersensitivity type II in heart, type III in kidneys and type IV in liver, as well as lungs were showing events of local mucosal immune responses.…”

Section: Resultsmentioning

confidence: 95%

An Immune Mediated Pathology And Tissue Immune Responses Induced By Human Tuberculus Cryglobulin In A Murine Models

Alzamily,

Shnawa,

Al-Azzawi

2017

JKAS

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Serum cryoglobulin were separated , characterized and partially purified from human pulmonary tuberculus patients. Three graded concentrations were made as;0.2,0.3,and 0.4 mg/ml .Four groups of mice, each of five were given 0.25ml. intramuscular in left and 0,25ml., in the right thigh to each animal in each group .the protocol consist of three successive doses from each concentration to each group in a week a part trend followed by one week leave .At the end of the protocol ,animals were sacrificed as well as the tissue blocks were collected, sectioned and processed for staining with H&E by the aim of tracing immune responses at tissue level .The immune response events were found as; Hyper-plasia of showed bronchus associated lymphoid tissue ,hyperplasia of epithelial cells of the bronchus walls, hyperplasia of macrophages in the alveolar spaces and accumulation of macrophages in the bronchial walls of the lungs .Cardiac muscles showed signs of carditis indicating type II hypersensitivity .Kidneys have shown inflammatory events indicating nephritis may be of serum sickness origin and edema can be of Arthus reaction, hypersensitivity type III. Liver sections were showing macrophage between blood vessels as pre-vascular kuff indicating delayed type hypersensitivity type IV. While splenic tissue sections were showing hypoplasia of lymphoid cells in the white pulp and /or deplition which may be attributed to the action of the regulatory T cells to the white pulp lymphoid cells. The tissue nature do affect the type of response as well as the intensity of the tissue responses were concentration dependent. Human cryoglobulin from tuberculus patients were found pathogenic for mice and the pathology was immune mediated as; Hypersensitivity types II,III, and IV as well as granuloma. The intensity of the responses were concentration dependent.

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Cryoglobulinemic glomerulonephritis — lessons from animal models

Cited by 9 publications

References 68 publications

A case of endocapillary proliferative glomerulonephritis with macrophages phagocytosing monoclonal immunoglobulin lambda light chain

A case of endocapillary proliferative glomerulonephritis with macrophages phagocytosing monoclonal immunoglobulin lambda light chain

The challenge of treating hepatitis C virus-associated cryoglobulinemic vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral agents

An Immune Mediated Pathology And Tissue Immune Responses Induced By Human Tuberculus Cryglobulin In A Murine Models

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