scholarly journals Belimumab for Immune-Mediated Necrotizing Myopathy Associated With Anti-SRP Antibodies: A Case Report and Retrospective Review of Patients Treated With Anti-B-Cell Therapy in a Single Center and Literature

2021 ◽  
Vol 12 ◽  
Author(s):  
Bei-Bei Cui ◽  
Yun-Ru Tian ◽  
Xin-Yue Ma ◽  
Geng Yin ◽  
Qibing Xie
Keyword(s):  
Literature Review ◽  
Cell Therapy ◽  
B Cell ◽  
Conventional Therapy ◽  
Signal Recognition Particle ◽  
Treatment Schedule ◽  
Cell Therapies ◽  
Necrotizing Myopathy ◽  
Immune Mediated

BackgroundImmune-mediated necrotizing myopathy (IMNM) is characterized by markedly elevated creatinine kinase and histologically scattered necrotic muscle fibers and generally associated with autoantibodies against signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coA-reductase (HMGCR). Poor clinical response to conventional therapies and relapses commonly occur in severe cases. Anti-B-cell therapies have been used in refractory/relapsing cases.MethodsThe characteristics of a patient with IMNM associated with anti-SRP antibodies including physical examination, laboratory tests, and disease activity assessment were evaluated. Conventional therapy, belimumab treatment schedule, and follow-up data were recorded. Medical records of IMNM patients treated in our department from September 2014 to June 2021 were reviewed to evaluate the efficacy and safety of anti-B-cell therapy for anti-SRP IMNM. A literature review of patients with anti-SRP IMNM treated with anti-B-cell therapies was performed.ResultsWe describe a case of a 47-year-old woman with IMNM associated with anti-SRP antibodies who relapsed twice after conventional therapy but showed good response and tolerance to belimumab at 28 weeks follow-up. In this review, three patients from our department were treated with rituximab. Two of the three patients rapidly improved after treatment. Twenty patients and five retrospective studies were included in the literature review. All patients were administered rituximab as an anti-B-cell drug.ConclusionDespite a lack of rigorous clinical trials, considerable experience demonstrated that anti-B-cell therapy might be effective for patients with IMNM associated with anti-SRP antibodies. Belimumab in association with steroids might be an encouraging option for refractory/relapsing cases.

scholarly journals Long-Term Follow-Up of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

2020 ◽  
Vol 38 (32) ◽  
pp. 3805-3815
Author(s):  
Kathryn M. Cappell ◽  
Richard M. Sherry ◽  
James C. Yang ◽  
Stephanie L. Goff ◽  
Danielle A. Vanasse ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T

PURPOSE Anti-CD19 chimeric antigen receptors (CARs) are artificial fusion proteins that cause CD19-specific T-cell activation. Durability of remissions and incidence of long-term adverse events are critical factors determining the utility of anti-CD19 CAR T-cell therapy, but long-term follow-up of patients treated with anti-CD19 CAR T cells is limited. This work provides the longest follow-up of patients in remission after anti-CD19 CAR T-cell therapy. METHODS Between 2009 and 2015, we administered 46 CAR T-cell treatments to 43 patients (ClinicalTrials.gov identifier: NCT00924326 ). Patients had relapsed B-cell malignancies of the following types: diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma (DLBCL/PMBCL; n = 28), low-grade B-cell lymphoma (n = 8), or chronic lymphocytic leukemia (CLL; n = 7). This report focuses on long-term outcomes of these patients. The CAR used was FMC63-28Z; axicabtagene ciloleucel uses the same CAR. Cyclophosphamide plus fludarabine conditioning chemotherapy was administered before CAR T cells. RESULTS The percentages of CAR T-cell treatments resulting in a > 3-year duration of response (DOR) were 51% (95% CI, 35% to 67%) for all evaluable treatments, 48% (95% CI, 28% to 69%) for DLBCL/PMBCL, 63% (95% CI, 25% to 92%) for low-grade lymphoma, and 50% (95% CI, 16% to 84%) for CLL. The median event-free survival of all 45 evaluable treatments was 55 months. Long-term adverse effects were rare, except for B-cell depletion and hypogammaglobulinemia. Median peak blood CAR-positive cell levels were higher among patients with a DOR of > 3 years (98/µL; range, 9-1,217/µL) than among patients with a DOR of < 3 years (18/µL; range, 0-308/μL, P = .0051). CONCLUSION Complete remissions of a variety of B-cell malignancies lasting ≥ 3 years occurred after 51% of evaluable anti-CD19 CAR T-cell treatments. Remissions of up to 9 years are ongoing. Late adverse events were rare.

scholarly journals Immune checkpoint inhibitor-associated myopathy: a clinicoseropathologically distinct myopathy

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Shahar Shelly ◽  
James D Triplett ◽  
Marcus V Pinto ◽  
Margherita Milone ◽  
Felix E Diehn ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Signal Recognition Particle ◽  
Ocular Involvement ◽  
Signal Recognition ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Coa Reductase

Abstract Immune checkpoint inhibitors have revolutionized the landscape of cancer treatment. Alongside their many advantages, they elicit immune-related adverse events, including myopathy, which potentially result in substantial morbidity if not recognized and treated promptly. Current knowledge of immune checkpoint inhibitor-associated myopathy is limited. We conducted a 5-year retrospective study of patients with immune checkpoint inhibitor-associated myopathy. Clinical features, survival and ancillary test findings were analysed and compared with those of immune-mediated necrotizing myopathy patients without immune checkpoint inhibitor exposure seen during the same time period. We identified 24 patients with immune checkpoint inhibitor-associated myopathy (median age 69 years; range 28–86) and 38 patients with immune-mediated necrotizing myopathy. Ocular involvement occurred in 9/24 patients with immune checkpoint inhibitor exposure, without electrodiagnostic evidence of neuromuscular transmission defect, and in none of the immune-mediated necrotizing myopathy patients (P &lt; 0.001). Myocarditis occurred in eight immune checkpoint inhibitor-associated myopathy patients and in none of the immune-mediated necrotizing myopathy patients (P &lt; 0.001). Median creatine kinase was 686 IU/l in the immune checkpoint inhibitor cohort (seven with normal creatine kinase) compared to 6456 IU/l in immune-mediated necrotizing myopathy cohort (P &lt; 0.001). Lymphopenia was observed in 18 and 7 patients with and without immune checkpoint inhibitor exposure, respectively (P &lt; 0.001). Myopathological findings were similar between patients with and without immune checkpoint inhibitor exposure, consisting of necrotic fibres with no or subtle inflammation. Necrotic fibres however arranged in clusters in 10/11 immune checkpoint inhibitor-associated myopathy patients but in none of the immune checkpoint inhibitor-naïve patients (P &lt; 0.001). Despite the lower creatine kinase levels in immune checkpoint inhibitor-exposed patients, the number of necrotic fibres was similar in both groups. Immune checkpoint inhibitor-associated myopathy patients had a higher frequency of mitochondrial abnormalities and less number of regenerating fibres than immune-mediated necrotizing myopathy patients (P &lt; 0.001). Anti-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle antibodies were absent in patients with immune checkpoint inhibitor exposure but positive in two-thirds of immune checkpoint inhibitor-naïve patients. Most patients with immune checkpoint inhibitor-associated myopathy responded favourably to immunomodulatory treatments, but four died from myopathy-related complications and one from myocarditis. Intubated patients had significantly shorter survival compared to non-intubated patients (median survival of 22 days; P = 0.004). In summary, immune checkpoint inhibitor-associated myopathy is a distinct, treatable immune-mediated myopathy with common ocular involvement, frequent lymphopenia and necrotizing histopathology, which contrary to immune-mediated necrotizing myopathy, is featured by clusters of necrotic fibres and not accompanied by anti-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle antibodies. Normal or mildly elevated creatine kinase level does not exclude the diagnosis.

scholarly journals Clinical And Morphological Improvement Of Lupus Nephritis Treated With Rituximab

Folia Medica ◽  
2014 ◽  
Vol 56 (4) ◽  
pp. 245-252 ◽  
Author(s):  
Maria E. Tsanyan ◽  
Sergey K. Soloviev ◽  
Stefka G. Radenska-Lopovok ◽  
Anna V. Torgashina ◽  
Ekaterina V. Nikolaeva ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Cell Therapy ◽  
Disease Activity ◽  
B Cell ◽  
Renal Biopsy ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Renal Biopsies

Abstract Aim: TO assess the effects of rituximab (RTM) therapy on clinical and morphologic activity of lupus nephritis (LN). Material and methods: The study included 45 patients with confirmed diagnosis of systemic lupus erythematosus (SLE), unaffected by previously received standard therapy with glucocorticoids (GCs) and cytostatics. The disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K); to assess the LN activity we used the SLICC RA/RE index. Forty-five patients with LN were given puncture renal biopsy prior to prescribing RTM; 16 patients had repeated renal biopsy 1 year and more after beginning the anti-B-cell therapy. LN was graded histologically in accordance with the WHO classification (2003) with indices of activity (AI) and chronicity (CI). Results: The predominant number of patients had class III - IV of LN. The repeated renal biopsies demonstrated that LN had undergone a transition into a more favourable morphologic class, which was associated, in most of these cases, with a positive therapeutic effect. The follow-up dynamics showed a statistically significant reduction of AI (p=0.006), and no statistically significant changes in the CI (p = 0.14). Conclusion: The long-term follow-up in the study has showed that repeated courses of anti-B-cell therapy with RTM have a positive effect both on SLE activity and generally on the renal process. The reduction of the morphologic class of LN as assessed in the repeated renal biopsies is a convincing proof for this. Eleven out of 16 patients experienced transition of the morphologic class into a more favourable type, which in most cases was combined with lower AI (p = 0.006). We found no evidence of increase in the CI (p = 0.14).

scholarly journals The Role of B Cells and B Cell Therapies in Immune-Mediated Liver Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Tamsin Cargill ◽  
Emma L. Culver
Keyword(s):  
B Cells ◽  
B Cell ◽  
Liver Diseases ◽  
Current Knowledge ◽  
Adaptive Immune System ◽  
Immune Defense ◽  
Future Research ◽  
Primary Biliary Cholangitis ◽  
Cell Therapies ◽  
Immune Mediated

B cells form a branch of the adaptive immune system, essential for the body’s immune defense against pathogens. B cell dysfunction has been implicated in the pathogenesis of immune mediated liver diseases including autoimmune hepatitis, IgG4-related hepatobiliary disease, primary biliary cholangitis and primary sclerosing cholangitis. B cells may initiate and maintain immune related liver diseases in several ways including the production of autoantibodies and the activation of T cells via antigen presentation or cytokine production. Here we comprehensively review current knowledge on B cell mechanisms in immune mediated liver diseases, exploring disease pathogenesis, B cell therapies, and novel treatment targets. We identify key areas where future research should focus to enable the development of targeted B cell therapies.

Clinical Characteristics of Immune-Mediated Necrotizing Myopathy with Autoantibodies Recognizing the Signal Recognition Particle: A Retrospective Study of a Chinese Cohort

2021 ◽  
Author(s):  
Qi Tang ◽  
Jinshen He ◽  
Feng Li ◽  
Jinwei Chen ◽  
Jing Tian ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Inflammatory Myopathy ◽  
Signal Recognition Particle ◽  
Idiopathic Inflammatory Myopathy ◽  
Lower Limbs ◽  
Hunan Province ◽  
Signal Recognition ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Chinese Cohort

Abstract Objective: Immune-mediated necrotizing myopathy (IMNM) with autoantibodies recognizing the signal recognition particle (SRP) patients tend to have prominent proximal weakness and infrequent extra-muscular involvement, especially interstitial lung disease (ILD). However, we reported a Chinese cohort of anti-SRP IMNM patients with relatively more frequent ILD.Methods: Anti-SRP IMNM patients from September 2016 to November 2019 were included according to the most recent European Neuromuscular Center criteria for IMNM. All sera for anti-SRP autoantibody and other myositis-related autoantibodies detection were obtained before the treatment initiation. Muscle strength, coexisting autoimmunity, complications including ILD, treatment and follow-up outcomes were also recorded. Univariate logistic regression was performed to determine variables predicting bad outcomes.Results: Of 271 patients with idiopathic inflammatory myopathy tested, we diagnosed 23 (8.5%) patients with anti-SRP IMNM. Muscle weakness was presented in 23 patients (100%) and generally worse in the lower limbs. ILD was observed in 50% anti-SRP IMNM patients. Predictor of bad outcomes identified by univariate logistic regression analysis was complicated ILD (odds ratio, 3.8).Conclusion: ILD tends to be more frequent in this Chinese anti-SRP IMNM cohort from Hunan province. Complicated ILD represents a risk factor for bad outcomes for anti-SRP IMNM.

scholarly journals Rituximab in the treatment of immune-mediated necrotizing myopathy: a review of case reports and case series

2021 ◽  
Vol 14 ◽  
pp. 175628642199891
Author(s):  
Anji Xiong ◽  
Guancui Yang ◽  
Zhuoyao Song ◽  
Chen Xiong ◽  
Deng Liu ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Case Reports ◽  
Signal Recognition Particle ◽  
High Dose ◽  
Signal Recognition ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Coa Reductase

Immune-mediated necrotizing myopathy (IMNM) is a group of immune-related myopathies characterized by progressive proximal muscle weakness, extremely high serum creatine kinase (CK) levels, and necrotic muscle fibers with a relative lack of inflammation. Treatment of IMNM is challenging, with most cases refractory to high-dose steroids in combination with multiple immunotherapies. The role of rituximab (RTX) for IMNM has been explored in isolated case reports and small series. The aim of this article was to perform a literature review of patients with IMNM treated with RTX and to evaluate RTX efficacy and safety. A total of 34 patients with IMNM were reviewed: 52.9% (18/34) with anti-signal recognition particle (SRP) antibodies and 47.1% (16/34) with anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies. Patient age at onset varied from 11 years to 81 years (mean 41 years). The majority of patients presented as a severe proximal muscle weakness and the peak level of CK varied from 3900 IU/L to 56,000 IU/L (mean 18,440 IU/L). Prior to RTX administration, all patients were treated with high-dose steroids and most were treated with multiple immunotherapies. The reason for initiating RTX was that 64.7% (22/34) of patients showed no improvement after previous treatments, and 35.3% (12/34) of patients relapsed when attempting to wean steroids or other immunosuppressive agents. With regard to RTX efficacy, 61.8% (21/34) of patients presented a response to RTX. Our data may support the use of RTX as an effective treatment strategy against IMNM resistant to steroids and multiple immunotherapies. Meanwhile, RTX as a first-line therapy could be a choice in IMNM, particularly in African Americans with anti-SRP antibody-positive subsets. ANA, antinuclear antibody; CK, creatine kinase; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; IMNM, immune-mediated necrotizing myopathy; MAC, membrane attack complex; MHC-I, major histocompatibility complex-I; RTX, rituximab; SRP, signal recognition particle.

scholarly journals Statins and Immune-Mediated Necrotizing Myopathy

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Mauro Turrin
Keyword(s):  
Present Article ◽  
Signal Recognition Particle ◽  
Intravenous Immunoglobulins ◽  
Pharmacological Therapy ◽  
High Dose ◽  
Signal Recognition ◽  
Drug Induced ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Diagnosis Classification

Statins are a well-recognized cause of a variety of skeletal myopathic effects, which generally resolve when discontinuing the treatment. Among autoimmune manifestations associated with statins, there is immune-mediated necrotizing myopathy (IMNM).The present article summarizes the main features of statin-related IMNM, describing diagnosis, classification, epidemiology, treatment, and the main autoantibodies detected.Statins are a well-recognized cause of a variety of skeletal myopathic effects, which generally resolve when discontinuing the treatment. Among autoimmune manifestations associated with statins, there is immune-mediated necrotizing myopathy (IMNM).The present article summarizes the main features of statin-related IMNM, describing diagnosis, classification, epidemiology, treatment, and the main autoantibodies detected.Although it is impossible to define the precise number, it evident that more than 550 statin-related IMNM cases have been described in the literature. Among IMNM, two forms must be distinguished: with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and with anti-signal recognition particle (SRP) antibodies. The differential diagnosis should be made between the IMNM and self-limited statin-related myopathy, drug-induced rhabdomyolysis, and nonautoimmune myopathies.Patients who have failed to normalize high creatine phosphokinase (CPK) after statin withdrawal should be tested for anti-HMGCR antibodies and, if these are positive, undergo muscle biopsy to confirm the diagnosis of IMNM. Pharmacological therapy of IMNM, not yet based on evidence, involves the use of high-dose corticosteroids, immunosuppressant drugs used alone or in combination, intravenous immunoglobulins (IVIg) or plasmapheresis.

scholarly journals Isolated Oropharyngeal Dysphagia as the Initial Presentation of Anti-SRP Immune-Mediated Necrotizing Myopathy

2020 ◽  
Author(s):  
Pat Korathanakhun ◽  
Thanyalak Amornpojnimman
Keyword(s):  
Muscle Weakness ◽  
Clinical Course ◽  
Signal Recognition Particle ◽  
Oropharyngeal Dysphagia ◽  
Signal Recognition ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Electrodiagnostic Study

A 51-year-old male initially presented with a progressive course of isolated oropharyngeal dysphagia prior to the clinical course of painful symmetrical proximal muscle weakness without sensory deficit which rendered him to wheelchairbound status within 5 months. The physical examination revealed symmetrical proximal muscle weakness without sensory symptoms. The initial serum creatine kinase was extremely high and the electrodiagnostic study revealed a myopathic pattern. A muscle biopsy of the left biceps suggested a diagnosis of immune-mediated necrotizing myopathy (IMNM) and the serum anti-signal recognition particle (SRP) autoantibody was finally detected. This case presented a rare form of anti-SRP IMNM in which isolated oropharyngeal dysphagia preceded the onset of proximal muscle weakness.

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