Rituximab Therapy for De Novo Mixed Cryoglobulinemia in Renal Transplant Patients

Basse, Grégoire; Ribes, David; Kamar, Nassim; Mehrenberger, Marion; Esposito, Laure; Guitard, Joëlle; Lavayssière, Laurence; Oksman, F; Dur, Dominique; Rostaing, Lionel

doi:10.1097/01.tp.0000183749.79424.b4

Cited by 74 publications

(39 citation statements)

References 19 publications

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“…Rituximab proved to be very effective in patients with HCV-MC [22][23][24][25][26][27][28][29][30] with clinical improvement in up to 60% of cases. [22][23][24][25][26][27][28][29] Although favorable outcomes have been reported with rituximab, little evidence is available about clinical and immunologic dynamics. Given the unclear nature of B-cell depletion, the multiple actions of B-cell regulation of T cells, and the unclear mechanism of autoimmunity in MC, we aimed to explore the immunologic dynamics in MC patients being treated with rituximab.…”

Section: Discussionmentioning

confidence: 99%

Restoration of peripheral immune homeostasis after rituximab in mixed cryoglobulinemia vasculitis

Saadoun

Rosenzwajg

Landau

et al. 2008

Blood

102

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Rituximab, an anti-CD20 monoclonal antibody, has been used to treat autoimmune disorders such as mixed cryoglobulinemia (MC). However, its mechanisms of action as well as the effects on cellular immunity remain poorly defined. We investigated the changes of peripheral blood B-and T-cell subsets, the clonal VH1-69 cells, as well as the cytokine profile following rituximab therapy. The study involved 21 patients with hepatitis C-related MC who received rituximab, of whom 14 achieved a complete response.Compared with healthy and hepatitis C virus (HCV) controls, pretreatment abnormalities in MC patients included a decreased percentage of naive B cells (P < .05) and CD4 ؉ CD25 ؉ FoxP3 ؉ regulatory T cells (P ‫؍‬ .02) with an increase in memory B cells (P ‫؍‬ .03) and plasmablasts (P < .05). These abnormalities were reverted at 12 months after rituximab. Clonal VH1-69 ؉ B cells dramatically decreased following treatment (32% ؎ 6% versus 8% ؎ 2%, P ‫؍‬ .01). Complete responders of rituximab exhibited an expansion of regulatory T cells (P < .01) accompanied with a decrease in CD8 ؉ T-cell activation (P < .01) and decreased production of interleukin 12 (IL-12; P ‫؍‬ .02) and interferon-␥ (IFN-␥; P ‫؍‬ .01). Our IntroductionChronic infection with hepatitis C virus (HCV) is the main cause of mixed cryoglobulinemia (MC) vasculitis, a potentially lifethreatening, systemic vasculitis. 1 MC reflects the expansion of B cells producing a pathogenic IgM with rheumatoid factor (RF) activity. MC may lead to clinical manifestations ranging from an MC syndrome (purpura, arthralgia, asthenia) to a more serious vasculitis with neurologic and renal involvement. 2 Oligoclonal or monoclonal B-cell expansions are significant molecular features of MC. 3,4 It is estimated that almost 10% of patients with MC progress to frank B-cell non-Hodgkin lymphoma (NHL). The overall risk of NHL in patients with HCV-MC is estimated to be 35 times higher than in the general population. 5 HCV is capable of infecting B-lymphocytes through LDL receptors or CD81. 6,7 The E2 envelope glycoprotein of HCV can bind CD81 B-cell surface protein. 6 CD81 has been demonstrated to play a costimulatory role in T-cell activation and an inhibitory role on natural killer (NK) cell on binding to E2 glycoprotein. 8,9 CD81 on B-cell surface may provide a strong stimulatory signal if activated as a part of a complex (CD19/CD21/CD81 complex) together with BCR activation. 10 The ability of E2 to directly engage CD81 alongside the binding of specific anti-E2 BCR may create a powerful stimulatory signal, promoting proliferation. Clonal B-cell expansion has been demonstrated in liver, blood, and bone marrow of patients with chronic HCV infection in the absence of overt B-cell malignancy. 3,4 The B-cell repertoire in cryoglobulinemic vasculitis is highly restricted. B-cell clones in HCV-MC often use the VH1-69 gene and VkA27 segment, which is also used by anti-E2 antibodies elicited by HCV. 11,12 Sequencing of these Ig variable regions has also revealed that they are the product o...

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Section: Discussionmentioning

confidence: 99%

Restoration of peripheral immune homeostasis after rituximab in mixed cryoglobulinemia vasculitis

Saadoun

Rosenzwajg

Landau

et al. 2008

Blood

102

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“…Encouraging results have been obtained in open-label studies and single case reports. RTX improves or cures various clinical manifestations of MC, including fatigue, purpura and skin ulcers, arthralgias and arthritis, glomerulonephritis (in about 90% of cases), peripheral neuropathy (in about 75% of cases), and hyperviscosity syndrome [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50] and [51]. RTX was also reported to be effective in some life-threatening cases of gastrointestinal vasculitis [43].…”

Section: Mixed Cryoglobulinemia-associated Glomerulonephritismentioning

confidence: 99%

Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases

Kattah¹,

Fervenza²,

Roccatello³

2013

Autoimmunity Reviews

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Rituximab is a monoclonal antibody to the CD20 antigen on B-cells that was initially designed and approved for the treatment of non-Hodgkin's B-cell lymphoma in 1997.In the last 15 years, it has emerged as a potent immunosuppressant for many immune-mediated diseases, beginning initially with rheumatoid arthritis, and now extending into several other fields, including clinical nephrology. Based on recent large clinical trials, it is FDA-approved for the treatment of ANCA-associated vasculitis and continues to be studied in off-label usage for many glomerular diseases, including membranous nephropathy, lupus nephritis, and mixed cryoglobulinemia. It has been used as a treatment in nephrotic syndrome in children and adults, including both minimal change disease and focal segmental glomerulosclerosis. Given its efficacy, tolerability and safety profile in comparison to more conventional treatment regimens, RTX is rapidly emerging as a critical treatment modality in glomerular disease.

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“…7,8 The efficacy of anti-CD20 monoclonal antibody (rituximab) has been reported in patients with HCV-MC vasculitis. 5,6,[10][11][12][13][14][15][16] A complete clinical response is achieved in 60% to 70% of cases, with cryoglobulin clearance in two-thirds of the patients. 5,6,10,11,[13][14][15][16] The absence of efficacy on HCV viral clearance and, furthermore, the potential increase in HCV viral load stress the need for combined antiviral therapy to block the HCV infection trigger.…”

Section: Introductionmentioning

confidence: 99%

Rituximab plus Peg-interferon-α/ribavirin compared with Peg-interferon-α/ribavirin in hepatitis C–related mixed cryoglobulinemia

Saadoun

Resche-Rigon

Sène

et al. 2010

Blood

245

148

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Rituximab Therapy for De Novo Mixed Cryoglobulinemia in Renal Transplant Patients

Abstract: We conclude that rituximab therapy is highly effective in cryoglobulin-related renal dysfunction in RT patients; however, due to chronic immunosuppression, this is at the expense of infectious complications.

Cited by 74 publications

References 19 publications

Restoration of peripheral immune homeostasis after rituximab in mixed cryoglobulinemia vasculitis

Restoration of peripheral immune homeostasis after rituximab in mixed cryoglobulinemia vasculitis

Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases

Rituximab plus Peg-interferon-α/ribavirin compared with Peg-interferon-α/ribavirin in hepatitis C–related mixed cryoglobulinemia

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