China
Africa
Explore chapters and articles related to this topic
Myocarditis
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
George Lazaros, Emilia Lazarou, Dimitris Tousoulis
In this difficult-to-treat patient group, EMB findings are of paramount importance to guide immunomodulatory and antiviral therapeutic options. Patients with inflammatory cardiomyopathy, i.e., virus-negative, inflammation-positive patients with persistent HF symptoms and depressed LVEF (<45%), despite optimal treatment for at least six months, are candidates for immunosuppression.8,14 Increased myocardial HLA expression and presence of circulating anti-heart antibodies further support immunosuppressive treatment.8 To date, two major placebo-controlled trials (the Myocarditis Treatment Trial and the Tailored Immunosuppression in Inflammatory Cardiomyopathy [TIMIC]) trial have evaluated treatment with prednisolone and azathioprine combinations for six months in this setting.59,60 The Myocarditis Treatment Trial was neutral,59 but viral genome search was not performed. In TIMIC, which included viral-negative patients, immunosuppression was beneficial (improved LVEF and left ventricular dimensions).60 Ongoing trials are expected to provide further data on this topic. In the context of immunomodulatory therapies, immunoadsorption is a procedure aiming at the removal of circulating antibodies. In myocarditis, autoantibodies appear to promote the progression of myocarditis to dilated cardiomyopathy. Initial experience from small studies showed a potential benefit with immunoadsorption; however, its role should be tested in larger studies.8
Hereditary and Acquired Causes of a Hypercoagulable State
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
As with the other anticoagulants, a functional screening assay is preferred. Several plasma-based clotting endpoint methods are commercially available. These generally involve addition of APC or snake venom PC activators to the test system, and measurement of PS activity in patient plasma diluted in PS-deficient plasma by a clotting endpoint. However, it has been shown that falsely low PS activity can be found in systems in which patient plasma is not diluted sufficiently (57, 58). This discrepancy is found in patients who carry the factor V Leiden mutation and is due to APC resistance prolonging the clotting time despite normal PS levels. Methods which add exogenous FVa or purify free PS by immunoadsorption before testing are minimally affected (59). Before interpreting PS levels, one should look at the APC resistance status and run the PS assay at at least two dilutions to look for the effect of inhibitors which could give rise to false PS activity. Because of these problems, some have suggested using free and total PS antigenic assays as screening methods (2). Most immunoassays for free PS utilize precipitation or immunoadsorption to separate free from bound forms. Recently a direct assay using a new monoclonal Ab specific for the free form has been described (60).
Closed-Loop Plasmapheresis
Published in James L. MacPherson, Duke O. Kasprisin, Therapeutic Hemapheresis, 2019
Michael J. Lysaght, Walter Samtleben, Baerbel Schmidt, Hans J. Gurland
The concept of immunosorption is illustrated in idealized form in Figure 4. An antibody or other molecule capable of reacting more or less specifically with a particular plasma component or protein class is bound to a suitable solid phase matrix. Plasma flows over the composite. Through the extremely specific lock-and-key mechanisms of immunochemistry, the bound antibody reacts with its cohort thereby removing it from solution while the remainder of the plasma freely returns to the patient. Analogous biochemical reactions such as that between heparin and low density lipoproteins (LDL), although not strictly immunochemical, are usually treated in the same category. The appeal of immunoadsorption is in its specificity. In principle, immunoadsorption is capable of removing the offending pathogen and nothing else. Thus the molecular hierarchy of the immune system need not be violated. Such a treatment is far more selective than pharmacological (i.e., cytotoxic) therapy which, like conventional plasma exchange, must be directed against broad classes of compounds to affect a single constituent protein. In fact, highly specific plasmapheresis might well prove preferable to broad-based cytotoxic therapy. Its simplicity could be combined with specificity, the present triage might be reserved, with plasmapheresis being employed as the treatment of first choice and not merely as the ultima ratio.
Therapeutic issues in Guillain–Barré syndrome
Published in Expert Review of Neurotherapeutics, 2023
Based on the current knowledge of the pathogenesis of GBS, several pathways seem interesting to target. Indeed, it has appeared quite clear that a complement deposition is a key event at least as a final critical step leading to nerve injury. Importantly, this has been suggested in the two main variants of GBS, which are AIDP and AMAN. Therefore, targeting different components of the complement pathways for therapeutic purposes makes sense. Despite partly disappointing results with Eculizumab (possibly due to the choice of the primary endpoint), this strategy seems worth exploring in the near future [24,25,45]. Ongoing clinical trials will hopefully demonstrate the usefulness of complement inhibition in GBS. Similarly, despite some gaps in the current knowledge of the pathogenesis of GBS, autoantibodies have been described, at least in AMAN, and are likely to be implicated in AIDP as well. Indeed, plasma exchange and immunoadsorption are apheresis techniques that, among other consequences, can remove antibodies from the plasma of individuals. Imlifidase, which is currently investigated as an add-on therapy in subjects with GBS would be a very good candidate to treat patients with aggressive forms of GBS, as it can very quickly cleave IgG from the serum of affected patients. If no serious adverse event occurs, due to reversible immunosuppression, one may speculate that this drug would become an important tool in the strategy of GBS treatment.
Memory B cells and long-lived plasma cells in AMR
Published in Renal Failure, 2022
Wenlong Yue, Jia Liu, Xiaohu Li, Luman Wang, Jinfeng Li
In patients with AMR, the DSAs produced in vivo are mainly anti-HLA and anti-non-HLA [59,80]. In the clinic, plasma exchange/immunoadsorption, as well as the injection of immunoglobulin-neutralizing antibodies, is often used to reduce plasma antibody levels in an effort to prevent graft rejection. Complementary pathway inhibitors [81], such as eculizumab, can also be used to alleviate the inflammatory pathological effects of antibody FC binding to complement proteins [82,83]. These inhibitors can reduce the incidence of rejection, to some extent, but the immune system undergoes a series of GC reactions that produce long-lived plasma cells that can persist in bone marrow for decades, even a lifetime, after kidney transplantation [51,64]. Therefore, the abovementioned medical intervention is only a temporary solution. It is an effective method to monitor the activity of long-lived plasma cells and memory B cells before the production of DSAs; subsequently, we can inhibit the body’s immune system through multiple immunouppressive regiments.
Emerging drugs for antibody-mediated rejection after kidney transplantation: a focus on phase II & III trials
Published in Expert Opinion on Emerging Drugs, 2022
Katharina A. Mayer, Klemens Budde, Bernd Jilma, Konstantin Doberer, Georg A. Böhmig
ABMR is a challenging post-transplant complication. Today, acute ABMR treatment relies on SOC treatment consisting of plasmapheresis and IVIG [11]. The evidence behind the use of such treatment is limited and mainly based on observational studies with or without historical control groups [22]. For immunoadsorption, a single trial has suggested efficacy. However, due to premature termination this trial only included 10 subjects [29]. Available evidence for adding rituximab to SOC is weak [81,84,86]. Similarly, the role of complement inhibitors is a matter of controversial discussion [49]. The results of an ongoing trial evaluating an anti-C1s monoclonal antibody are awaited [52]. Late (chronic) ABMR may be particularly challenging. In this indication, TRITON and BORTEJECT have failed to demonstrate efficacy of IVIG/rituximab or bortezomib, respectively [84,114]. Plasmapheresis and IVIG is not recommended and, currently, optimizing baseline immunosuppression and medical therapy is the only option outside investigational studies [11]. But even for this recommendation evidence is lacking. For ABMR treatment, there are promising concepts in the pipeline and systematic trials are currently underway. These include, among others, monoclonal antibodies against IL-6/IL-6 R [36,104], imlifidase for IgG cleavage [46] or the CD38 antibody felzartamab [127]. These studies will hopefully help to develop an optimal treatment schedule for ABMR.