- Early neutropenia with thrombocytopenia following alemtuzumab treatment for multiple sclerosis: case report and review of literature. [Journal Article]
- CNClin Neurol Neurosurg 2018 Nov 03; 175:134-136
- Alemtuzumab is a monoclonal antibody targeting the CD52 antigen used in the treatment of relapsing-remitting multiple sclerosis (RRMS). CD52 is expressed by lymphocytes and monocytes but less by neut...
Alemtuzumab is a monoclonal antibody targeting the CD52 antigen used in the treatment of relapsing-remitting multiple sclerosis (RRMS). CD52 is expressed by lymphocytes and monocytes but less by neutrophils and not by platelets. We present a case of a 38-year-old woman with RRMS who developed early neutropenia with thrombocytopenia after alemtuzumab infusion. She had no fever or symptoms of infection or purpura. After two weeks her haematological disorders spontaneously resolved. We reported the first case of neutropenia and thrombocytopenia as a possible event occurring after alemtuzumab infusion in MS patients, even if in a mild grade. So, we recommend to not underestimate these two conditions.
- Hypercalcaemia with undetectable parathormone levels. [Journal Article]
- BMJBMJ 2018 Nov 08; 363:k4074
- Vitiligo after alemtuzumab treatment: Secondary autoimmunity is not all about B cells. [Journal Article]
- NeurNeurology 2018 Nov 07
- CONCLUSIONS: The 3 cases represent a detailed description of vitiligo as a T-cell-mediated secondary autoimmune disease following alemtuzumab treatment. The prevailing concept of unleashed B-cell responses might therefore not cover all facets of alemtuzumab-related secondary autoimmunity. Mechanistic studies, especially on TCR repertoire, might help clarify the underlying mechanisms.
- Severe B cell-mediated disease activation despite two cycles of alemtuzumab in a patient with multiple sclerosis. [Journal Article]
- MSMult Scler 2018 Nov 07; :1352458518810261
- Alemtuzumab is a potent monoclonal CD52 antibody used to treat patients with multiple sclerosis (MS). However, recent literature reports have described paradoxical activation of B cell-mediated disea...
Alemtuzumab is a potent monoclonal CD52 antibody used to treat patients with multiple sclerosis (MS). However, recent literature reports have described paradoxical activation of B cell-mediated disease within 1 year of the first cycle of alemtuzumab. We raise awareness that severe B cell-mediated disease activation could develop, even after two cycles of alemtuzumab, in some vulnerable MS patients; therefore, individualized therapeutic strategies should be considered in clinical practice. We also propose that a novel regulatory B-cell subset may be a candidate for a predictive biomarker of disease activation in MS patients treated with alemtuzumab.
- Autoimmune Thyroid Disease in Islet Transplant Recipients Discontinuing Immunosuppression Late After Lymphodepletion. [Journal Article]
- JCJ Clin Endocrinol Metab 2018 Nov 05
- CONCLUSIONS: Despite routine use of alemtuzumab, clinical presentations of AITD seem to be uncommon in CIT patients receiving immunosuppression. However, AITD can develop following withdrawal of immunosuppression, highlighting the need for careful thyroid surveillance in this population.
- Lambert-Eaton myasthenic syndrome associated with alemtuzumab administration. [Journal Article]
- MSMult Scler Relat Disord 2018 Oct 22; 27:131-132
- CONCLUSIONS: Alemtuzumab treatment can result in the development of neurologic autoimmune conditions that could mimic MS progression.
- Cost-effectiveness of alemtuzumab and natalizumab for relapsing-remitting multiple sclerosis treatment in Iran: decision analysis based on an indirect comparison. [Journal Article]
- JMJ Med Econ 2018 Oct 31; :1-30
- CONCLUSIONS: Alemtuzumab was dominant in the treatment of RRMS compared with natalizumab due to lower total cost, greater efficacy and slowing of disease progression, and lower rate of relapses over a 20-year time horizon in Iran. Comparative head-to-head trials and long-term follow-up are needed to confirm these results.
- IL-21 Biased Alemtuzumab Induced Chronic Antibody-Mediated Rejection Is Reversed by LFA-1 Costimulation Blockade. [Journal Article]
- FIFront Immunol 2018; 9:2323
- Despite its excellent efficacy in controlling T cell mediated acute rejection, lymphocyte depletion may promote a humoral response. While T cell repopulation after depletion has been evaluated in man...
Despite its excellent efficacy in controlling T cell mediated acute rejection, lymphocyte depletion may promote a humoral response. While T cell repopulation after depletion has been evaluated in many aspects, the B cell response has not been fully elucidated. We tested the hypothesis that the mechanisms also involve skewed T helper phenotype after lymphocytic depletion. Post-transplant immune response was measured from alemtuzumab treated hCD52Tg cardiac allograft recipients with or without anti-LFA-1 mAb. Alemtuzumab induction promoted serum DSA, allo-B cells, and CAV in humanized CD52 transgenic (hCD52Tg) mice after heterotopic heart transplantation. Additional anti-LFA-1 mAb treatment resulted in reduced DSA (Fold increase 4.75 ± 6.9 vs. 0.7 ± 0.5; p < 0.01), allo-specific B cells (0.07 ± 0.06 vs. 0.006 ± 0.002 %; p < 0.01), neo-intimal hyperplasia (56 ± 14% vs. 23 ± 13%; p < 0.05), arterial disease (77.8 ± 14.2 vs. 25.8 ± 20.1%; p < 0.05), and fibrosis (15 ± 23.3 vs. 4.3 ± 1.65%; p < 0.05) in this alemtuzumab-induced chronic antibody-mediated rejection (CAMR) model. Surprisingly, elevated serum IL-21 levels in alemtuzumab-treated mice was reduced with LFA-1 blockade. In accordance with the increased serum IL-21 level, alemtuzumab treated mice showed hyperplastic germinal center (GC) development, while the supplemental anti-LFA-1 mAb significantly reduced the GC frequency and size. We report that the incomplete T cell depletion inside of the GC leads to a systemic IL-21 dominant milieu with hyperplastic GC formation and CAMR. Conventional immunosuppression, such as tacrolimus and rapamycin, failed to reverse AMR, while co-stimulation blockade with LFA-1 corrected the GC hyperplastic response. The identification of IL-21 driven chronic AMR elucidates a novel mechanism that suggests a therapeutic approach with cytolytic induction.
- IL-15 enhanced antibody-dependent cellular cytotoxicity mediated by NK cells and macrophages. [Journal Article]
- PNProc Natl Acad Sci U S A 2018 Oct 29
- The goal of cancer immunotherapy is to stimulate the host immune system to attack malignant cells. Antibody-dependent cellular cytotoxicity (ADCC) is a pivotal mechanism of antitumor action of clinic...
The goal of cancer immunotherapy is to stimulate the host immune system to attack malignant cells. Antibody-dependent cellular cytotoxicity (ADCC) is a pivotal mechanism of antitumor action of clinically employed antitumor antibodies. IL-15 administered to patients with metastatic malignancy by continuous i.v. infusion at 2 μg/kg/d for 10 days was associated with a 38-fold increase in the number and activation status of circulating natural killer (NK) cells and activation of macrophages which together are ADCC effectors. We investigated combination therapy of IL-15 with rituximab in a syngeneic mouse model of lymphoma transfected with human CD20 and with alemtuzumab (Campath-1H) in a xenograft model of human adult T cell leukemia (ATL). IL-15 greatly enhanced the therapeutic efficacy of both rituximab and alemtuzumab in tumor models. The additivity/synergy was shown to be associated with augmented ADCC. Both NK cells and macrophages were critical elements in the chain of interacting effectors involved in optimal therapeutic responses mediated by rituximab with IL-15. We provide evidence supporting the hypothesis that NK cells interact with macrophages to augment the NK-cell activation and expression of FcγRIV and the capacity of these cells to become effectors of ADCC. The present study supports clinical trials of IL-15 combined with tumor-directed monoclonal antibodies.
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- Restoration of regulatory B cell deficiency following alemtuzumab therapy in patients with relapsing multiple sclerosis. [Journal Article]
- JNJ Neuroinflammation 2018 Oct 30; 15(1):300
- CONCLUSIONS: Our results highlight the preferential reconstitution of Bregs as a possible mechanism of action of alemtuzumab and CD19+CD24hiCD38hi cells as a potential biomarker for disease activity.