Probiotics and Eating Disorders
Martin Colin R, Derek Larkin in Probiotics in Mental Health, 2018
Substances called autoantibodies may also play a significant role here. An autoantibody is an antibody that reacts against normal substances present in the organism, and is commonly found in autoimmune diseases. AutoAbs directed against stress related hormones: alpha-melanocyte-stimulating hormone (a-MSH—a neuropeptide that helps to regulate appetite and emotion) and adrenocorticotrophic hormone (ACTH) are higher in patients with eating disorders compared with controls. Fetissov and colleagues (2008) found that the level of one of these autoantibodies (AutoAbs a-MSH) was directly correlated with higher scores of restrictive eating behaviour as measured by the Eating Disorders Inventory-2 (Garner, 1991). They also found significant linear (positive and negative) correlations between autoAbs directed against four other key neuropeptides (ACTH, a-MSH, Oxytocin, Vasopressin) in patients with AN and BN. Data from other studies supports the finding that levels of AutoAbs are altered in different ways in AN compared to obesity (Kalra, 2008). There is also growing support for this theory from animal models, for example intracerebral injection of a-MSH IgA autoABs in rat models produces acute bulimic and anxious responses (Lee et al., 2008; Fetissov et al., 2008).
Tolerance and autoimmunity
Gabriel Virella in Medical Immunology, 2019
Autoantibody-associated diseases are characterized by the presence of autoantibodies in the individual's serum and by the deposition of autoantibodies in tissues. Antibodies with high affinity for the antigen are considered to be more pathogenic because they form stable immune complexes (ICs) that can activate complement more effectively. Other characteristics of the antibodies and corresponding agents may play a determinant pathogenic role. For example, DNA antibodies, very prevalent in SLE, have a weak positive charge at physiological pH and bind to the negatively charged glomerular basement membrane, which also binds DNA. Such affinity of antigens and antibodies for the glomerular basement membrane creates the ideal conditions for in situ IC formation and deposition, which is usually followed by glomerular inflammation. Some DNA antibodies cross-react with NMDA receptors in the brain and cause pathology. Finally, autoantibodies may bind only to cells and tissues that have been exposed to a stressor such as ischemia, activate complement, and cause tissue injury. This may explain why titers of autoantibodies almost never correlate with autoimmune disease severity.
Human Monoclonal Autoantibodies
Thomas F. Kresina in Monoclonal Antibodies, Cytokines, and Arthritis, 2020
Most of the T cell-reactive antibodies we isolated show reactivity with other hematopoietic and some nonhematopoietic cell types. Therefore, it is possible that antilymphocyte autoantibodies may cause wide-ranging functional effects. Similarly, Shoenfeld et al. have found that the DNA-reactive monoclonal antibodies that they have isolated also show a remarkable degree of polyspecificity. That is, individual DNA-reactive monoclonal antibodies bind to a wide variety of targets, including native DNA, single-stranded DNA, synthetic polynucleotides, cardiolipin, lymphocytes, platelets, cytoskeletal proteins, and some mycobacterial antigens (6,43–46). However, there is significant variability from antibody to antibody in the precise pattern of cross-reactivity. The remarkable cross-reactivity of human monoclonal autoantibodies raises interesting questions regarding the original stimulus for such antibodies and raises the possibility that a single autoantibody could be involved in a wide range of clinical effects.
Pathogenesis, diagnosis and treatment of paraneoplastic neurologic syndromes
Published in Expert Review of Neurotherapeutics, 2021
In contrast to PNS with onconeural antibodies, paraneoplastic syndromes associated with autoantibodies to surface-binding autoantibodies respond much better to immunosuppressive treatment [20]. In these syndromes, the autoantibody itself is the pathogenic agent or contributes significantly to the underlying pathophysiology. The first-line treatment of PNS with surface/receptor antibodies includes steroids, intravenous immunoglobulins, plasma exchange, or a combination of these treatments [80,116,117]. However, among patients with suspected paraneoplastic and non-paraneoplastic autoimmune encephalitis, treatment should not be delayed until autoantibody test results are available. If viral and bacterial causes are excluded, prompt immunosuppressive treatment should be initiated. If the patient does not respond to a first-line treatment, rituximab or cyclophosphamide should be considered as an escalation treatment [15,118]. Tocilizumab, an anti-interleukin-6 antibody, was effective in the management of patients with autoimmune encephalitis refractory to rituximab [119]. In general, about 60–80% of the patients experience significant improvements within two years, although relapses may occur in 15–30% [116]. There is also an ongoing discussion as to whether a more aggressive early immunosuppression leads to a reduced relapse rate [80,117].
Plasmablasts and neuroimmunological disorders
Published in Immunological Medicine, 2019
Norio Chihara, Riki Matsumoto, Takashi Yamamura
On the other hand, about half of anti-NMDA receptor encephalitis is paraneoplastic neurologic syndrome related to ovarian teratoma, and the recurrence is about 15%, and in those cases, ovarian teratoma can recur [23]. It is also well known that autoantibodies against voltage-gated calcium channels (VGCC) cause Lambert–Eaton myasthenic syndrome, typically as a paraneoplastic neurologic syndrome due to small-lung cell carcinomas, inhibiting pre-synaptic calcium channels which are required for acetylcholine supply in the neuromuscular junction [24]. There are also cases of thymoma-related MG5 as well as tumors associated with NMO [25]. In these cases, autoantibody production is seen as a normal immune response in a cross-reaction against tumor antigens (non-self antigens), where immune background may be different from autoantibodies positive cases without tumor. In the future, it is expected that the characteristics of PB that produce autoantibodies in neuroimmunological disease patients will be clarified that can lead to the development of therapeutics based on its pathological background.
Anti-DFS70 antibodies: an update on our current understanding and their clinical usefulness
Published in Expert Review of Clinical Immunology, 2019
Michael Mahler, Luis E. Andrade, Carlos A. Casiano, Kishore Malyavantham, Marvin J. Fritzler
Since it is evident that some serum samples generate a DFS pattern in the HEp-2 IIF test but do not react with the recombinant DFS70/LEDGFp75, it is likely that other proteins are the target of autoantibodies. Due to the apparently identical IIF staining pattern, it is possible that such sera recognize other proteins of the macromolecular complex representing interacting partners of DFS70/LEDGFp75 are the autoantibody targets. Interestingly, one of these partners is MeCP2 [22], which based on its migration in Western blotting gels happens to have the same molecular mass as DFS70/LEDGFp75. As expected, monoclonal antibodies to MeCP2 have shown to produce an IIF pattern that is indistinguishable from DFS. Consequently, MeCP2 was considered to be a potential target of autoantibodies in human sera. However, it was reported that MeCP2 is not a major autoantigenic target in human sera [22]. Other mammalian proteins that interact with DFS70/LEDGFp75 and could potentially generate antibodies that produce an IIF pattern similar to DFS include the c-MYC binding protein JPO2/CDCA7L (53 kDa), the mixed lineage leukemia protein 1 (MLL1, 586 kDa) and its associated protein Menin (68 kDa), the Cdc7-ASK/DBF4 kinase (77 kDa), and other recently identified interacting partners [23,24]. Studies to investigate autoantibodies to these targets are of paramount importance in trying to achieve a clearer picture of the entire DFS autoantibody repertoire.
Related Knowledge Centers
- Antibody
- Protein
- Immune System
- Autoimmune Disease
- Lupus Erythematosus
- B Cell
- Clonal Deletion
- Graves' Disease
- Hashimoto'S Thyroiditis
- Arthritis