Changes in regulatory T cells after rituximab in two patients with refractory myasthenia gravis

Catzola, Valentina; Battaglia, Alessandra; Buzzonetti, Alexia; Fossati, Marco; Scuderi, Flavia; Fattorossi, Andrea; Evoli, Amelia

doi:10.1007/s00415-013-6987-y

Cited by 19 publications

(18 citation statements)

References 14 publications

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“…A total of 47 publications were reviewed, of which 28 were single case reports and 19 reporting 2 or more patients (range 2–22) . Only data available on unique cases from all published reports were included; data from publications that reported cases presented in earlier reports were excluded.…”

Section: Resultsmentioning

confidence: 99%

Rituximab treatment of myasthenia gravis: A systematic review

et al. 2017

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Rituximab is a chimeric mouse/human anti-CD20 monoclonal immunoglobulin. We reviewed the efficacy and safety of rituximab in 169 myasthenia gravis (MG) patients from case reports and series. Antibodies to the acetylcholine receptor (AChR) were present in 59% and muscle-specific tyrosine kinase (MuSK) in 34%. Modified Myasthenia Gravis Foundation of America postintervention scale of minimal manifestations (MM) or better occurred in 44%, and combined pharmacologic and chronic stable remission in 27% overall; MM or better was achieved in 72% of MuSK MG and 30% of AChR MG (P < 0.001). Posttreatment relapses decreased more in MuSK MG (P = 0.05). Response predictors were MuSK MG, less severe disease, and younger age at treatment. Among a responder subset, 26% of AChR and 82% of MuSK MG patients showed decreased posttreatment antibody titers. Rituximab was generally well tolerated. Detectable serum rituximab and depleted CD20 B-cells were observed up to 20 and 16 weeks, respectively, after 4 weekly infusions. Muscle Nerve 56: 185-196, 2017.

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Section: Resultsmentioning

confidence: 99%

Rituximab treatment of myasthenia gravis: A systematic review

et al. 2017

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“…Low numbers of regulatory T cells in the peripheral blood correlates with autoimmunity and granulomatous disease, including granulomatous lung disease, in patients with CVID [19–22]. Azathioprine and rituximab, which are used to treat GLILD, have been shown to increase the numbers of regulatory T cells [23,24]. We therefore hypothesize that the lack of regulatory T cells in the lungs of patients with GLILD is a contributing factor in the underlying pathogenesis of this disorder.…”

Section: Discussionmentioning

confidence: 99%

Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency—histologic and immunohistochemical analyses of 16 cases

Rao¹,

Mackinnon²,

Routes³

2015

Human Pathology

113

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Common Variable Immunodeficiency (CVID) is a primary immunodeficiency of unknown etiology characterized by low serum IgG, a decreased ability to make specific antibodies, and variable T cell defects. Approximately 20% of patients with CVID develop clinical evidence of a diffuse parenchymal lung disease with a constellation of histopathological findings termed granulomatous and lymphocytic interstitial lung disease (GLILD). In this study, we characterized the histological and immunohistochemical features in a series of 16 cases diagnosed by open lung biopsy. Peribronchiolar and interstitial lymphocytic infiltration, granulomatous inflammation and organizing pneumonia were consistent features; interstitial fibrosis with architectural remodeling was also found in a subgroup of patients. By immunohistochemistry, a predominance of CD4+ T lymphocytes with variable numbers of CD8+ T cells and B cells were present, with a striking absence of FOXP3 positive T regulatory cells. This heretofore unrecognized immunohistochemical finding, needs further investigation for a potential role in the pathogenesis of the condition. The presence of interstitial fibrosis with or without architectural remodeling in a subset of patients also needs additional study, for effect on prognosis.

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“…The repopulation of this tolerogenic B cell subset could contribute to effects of RTX through secretion of IL‐10 and the expansion of the T reg compartment. Consistent with this view, a comparative case report displayed a long‐lasting increase of circulating T reg cells in a responsive MuSK + MG patient, while inconsistent fluctuations of T reg cells were recorded in the RTX‐resistant AChR + MG patient . In addition, as IFN‐γ–secreting B cells are able to suppress T reg cell differentiation, RTX could promote the expansion of the T reg compartment through conventional B cell depletion.…”

Section: Rtx In Mgmentioning

confidence: 65%

“…In this way, it could be determined whether RTX treatment could modify the specific T cell response in MuSK + MG. Besides, though several studies have shown that RTX can expand T reg cells, evidence for the antigen specificity of this response is lacking, and the analysis of TCR repertoire in this subset could add relevant information . Such an analysis might select TCR rearrangements more responsive to RTX, thus facilitating personalized treatment.…”

Section: Rtx In Mgmentioning

confidence: 99%

Rituximab in myasthenia gravis: a “to be or not to be” inhibitor of T cell function

Marino

Bartoccioni

Alboini

et al. 2018

Annals of the New York Academy of Sciences

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In recent years, rituximab (RTX), a monoclonal antibody that binds the B lymphocyte membrane protein CD20, has been increasingly used for the treatment of autoimmune diseases, with the rationale of destroying pathogenic B lymphocytes and decreasing autoantibody formation. Surprisingly, RTX has also proven effective in predominantly T cell-mediated diseases, raising the question whether additional mechanisms may play roles in determining the therapeutic response. Here, we review the current literature on the effects of RTX in autoimmune diseases, with special emphasis on myasthenia gravis (MG). To elicit a complete and effective immune response, B and T lymphocytes cooperate in a loop in which they affect each other. Disruption of this cross talk has profound effects on the immune system. RTX is likely to affect the whole spectrum of B cell function, including antigen presentation, cytokine production, and T cell stimulation. In addition, as a small subset of T lymphocytes expresses CD20, its direct targeting by RTX may contribute to the therapeutic effect. Owing to its distinctive immune characteristics, MG proved to be a useful model to investigate the multifaceted implications of B cell depletion.

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Changes in regulatory T cells after rituximab in two patients with refractory myasthenia gravis

Cited by 19 publications

References 14 publications

Rituximab treatment of myasthenia gravis: A systematic review

Rituximab treatment of myasthenia gravis: A systematic review

Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency—histologic and immunohistochemical analyses of 16 cases

Rituximab in myasthenia gravis: a “to be or not to be” inhibitor of T cell function

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