This happens when something goes wrong with the immune system and mistakenly attacks a healthy part of the body, in this case, the brain or spinal cord of the nervous system. In multiple sclerosis, the immune system attacks the layer that surrounds and protects the nerves, called the myelin sheath. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to a variety of neurological and autoimmune manifestations.
There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classic autoimmune disease, even though many authors state this in their description of the disease. We show the evidence that supports and refutes the autoimmune hypothesis. In addition, we present an alternative hypothesis based on virus infection to explain the pathogenesis of MS.
Multiple sclerosis (MS) is a long-term (chronic) central nervous system disease. It's thought to be an autoimmune disorder, a condition in which the body attacks itself by mistake. Multiple sclerosis is an unpredictable disease that affects people differently. Some people with multiple sclerosis may have only mild symptoms.
Others may lose the ability to see clearly, write, speak, or walk when communication between the brain and other parts of the body is interrupted. The cause of multiple sclerosis is unknown. It is considered an immune-mediated disease in which the body's immune system attacks its own tissues. In the case of multiple sclerosis, this malfunction of the immune system destroys the fatty substance that covers and protects nerve fibers in the brain and spinal cord (myelin).
Multiple sclerosis (MS) is an autoimmune disease. With these conditions, the immune system mistakenly attacks healthy cells. In people with multiple sclerosis, the immune system attacks myelin cells, the protective layer that surrounds nerves in the brain and spinal cord. Scientists believe that MS is triggered by a combination of one or more environmental factors acting on a genetically susceptible individual.
These environmental factors include an unknown foreign substance (an antigen), such as a virus or toxin. In autoimmune diseases, researchers have identified the specific antigen responsible. No specific antigens have been identified in MS. However, most experts believe that MS is an autoimmune disease, although specific antigens have not been identified.
Autoimmune comorbidities occur frequently in multiple sclerosis (MS). They can arise as a result of genetic susceptibility to autoimmunity. Certain pathological mechanisms are common to several autoimmune conditions. In the presence of comorbid autoimmune conditions, certain therapies for MS may be preferable to others.
Autoimmune comorbidity associated with MS could be a factor in predicting the response to specific therapies for MS. Interferon beta treatment has been reported to precipitate immune-mediated abnormalities or exacerbate existing autoimmune diseases. By comparison, there are fewer reported cases of treatment-related comorbidities related to autoimmune disease in patients taking glatiramer acetate. Knowledge of factors that influence autoimmune comorbidities can provide information about the complex pathogenesis of MS and help inform treatment options.
The most convincing evidence that immunopathogenesis exists in MS comes from the surprising benefit seen when lymphocyte migration to the CNS is blocked with natalizumab, or when lymphocytes are trapped in regional lymph nodes with fingolimod, 7,8.It is difficult to rule out the fact that, when monocytes are prohibited from entering the CNS, the rate of relapse and the rate of progression of disability in MS are attenuated. Another challenge to the hypothesis of the autoimmune pathogenesis of MS has arisen following the findings that some of the antibodies identified in the cerebrospinal fluid of MS patients are not directed against any of the known myelin proteins. 9 A mitigating argument is that some of these antibodies may be attacking myelin lipids and carbohydrates that are known to play a role in autoimmune inflammation,10 One hypothesis is that demyelination is caused by oligodendrologlial apoptosis and that inflammation is simply a secondary event initiated to eliminate the products of myelin degeneration, 11 Whether it's apoptosis or an infection that triggers the inflammatory response, there is evidence of an unmistakable immune fingerprint at the site of the sickness. Inhibiting the entry of immune cells into the brain provides great benefits, as demonstrated by natalizumab, its effects and its underlying mechanism of action.
[7] Another confounding factor in the pathogenesis of MS lies in the treatment options available. Treatments for controlling MS relapses, such as systemic steroids and adrenocorticotrophic hormone (ACTH), are also widely accepted for other autoimmune conditions, where they can be used for the maintenance or treatment of acute exacerbations. The potential modifying role of ACTH in MS as a disease modifier needs to be further studied. Disease-modifying treatments for multiple sclerosis, such as interferon beta (IFN), glatiramer acetate (GA), natalizumab, fingolimod, and BG-12, have mostly unknown or understudied applications for other autoimmune conditions (with the exception of the BG-12 analog, which is approved for use in psoriasis, and natalizumab, which is approved for use in Crohn's disease).
GA shows promise in inflammatory bowel disease, 12 Effect of autoimmune comorbidities on multiple sclerosis: diagnosis, treatment and outcomes Comorbidities are an important topic in MS. They considerably worsen the impact of the disease and some of them (for example,. For example, in the presence of comorbid inflammatory bowel disease or uveitis, the use of biological therapies against tumor necrosis factor (TNF) should be avoided. Similarly, it would not be advisable to treat MS with natalizumab in a patient who has previously received immunosuppressive therapy for MS or for a comorbid autoimmune condition,18. Insufficient attention has been paid to research on the diagnosis and treatment of autoimmune comorbidities in the MS population.
The resulting information gap adds greater complexity to disease management. Addressing this gap is important, especially because early recognition and treatment of comorbid conditions can improve prognosis, help define the course of the disease, and allow for better-informed and individualized treatment decisions. Studies on autoimmune comorbidities in multiple sclerosis Until recently, clinical data related to the co-occurrence of autoimmune diseases in MS were based predominantly on uncontrolled case series or small case-control studies, and few studies took into account confounding factors such as age and sex. There are many difficulties inherent to these studies, such as selection or verification bias.
The results may differ depending on the conditions being included and the way the diagnosis is arrived at. [18] In ethnically mixed populations, such as North America, the use of spouses as controls allows for ethnic pairing. [19] The use of such controls is quite common in genetic studies, but much less widespread in clinical trials20—2.However, because MS is significantly more prevalent in women, this approach may increase a potential gender imbalance between cases and controls. In a family study in which several members had been diagnosed with MS (176 families, 386 people with MS, and 1,107 first-degree family members), participants were studied to determine if they had a history of coexisting autoimmune disorders (see figure.
Of the 1,107 first-degree family members, 64 percent had a history of autoimmune diseases. The most commonly reported autoimmune conditions in patients with multiple sclerosis and their families were Hashimoto's thyroiditis, psoriasis, and inflammatory bowel disease (IBD). A Danish registry study showed that autoimmune disorders tended to coexist with MS and to occur in the families of MS patients, but that this was not a uniform phenomenon across diseases. 25 patients with type 1 diabetes were found to have more than three times the risk of developing MS.
Compared to the general Danish population, MS patients were found to have a higher incidence of type 1 diabetes, ulcerative colitis, autoimmune thyroiditis, and pemphigoid, but a lower incidence of RA. MS and RA appear to have a reduced likelihood of coexistence, 26 This inverse association between MS and RA was also found in a population-based cohort study used in the UK General Practice Research Database, 27 While previous studies show similarities, there are inconsistencies in the data on the association between thyroiditis and MS. Autoimmune thyroiditis was found to be significantly more prevalent in male MS patients than in male controls (9.4 versus 1.9%; P%3d0.0). However, there were no significant differences in the prevalence of autoimmune thyroiditis between patients with multiple sclerosis and control women (8.7 versus 9.2%).
More studies are required to determine the cause of this increased prevalence of autoimmune thyroiditis in men with MS. 28 This finding illustrates the importance of avoiding gender bias in studies on comorbidities in MS. A large North American study found no association between multiple sclerosis and asthma,24 although asthma associated with chronic obstructive pulmonary disease was excluded from the study, presumably to select it specifically for atopic asthma. However, a retrospective study conducted in Wales established an inverse relationship between asthma and MS (odds ratio 0.33; 95% confidence interval: 0.15—0.7).
In summary, the data published to date show a marked association between MS and certain autoimmune comorbidities. Table 1 provides an overview of some of the most common autoimmune diseases and their degree of association with MS. Future studies should analyze comorbidities and take into account the modifying effects of socioeconomic status, ethnicity, and cultural factors in MS. 33 Studies investigating genetic susceptibility to MS have identified a number of genomic regions and specific genes of interest, most of which are associated with the immune response, in particular the MHC region on chromosome 634 to 38. Although epidemiological data suggest an inverse association between MS and RA, genome-wide association studies (GWAS) have found that MS and RA share many gene factors, 39 However, certain genetic loci of susceptibility to autoimmune diseases, described in the GWAS, they are not associated as much with MS as with other autoimmune diseases; for example, the PTPN22 risk allele has been strongly associated with type 1 diabetes, RA and thyroiditis, but not with MS, 40 In addition to genetic factors, synergistic interactions between environmental factors that trigger autoimmunity, such as Epstein-Barr virus infection or vitamin D deficiency.
may underlie comorbidities, inactivation of the vitamin D 18 receptor and vitamin D-deficient mice have an excess of a type of effector T cell that has been implicated in the pathology of MS and IBD,41 In addition, smoking is associated with an increased risk of comorbid autoimmune disease in MS. 3.Tables 2 and 3 show that there are more reported cases of autoimmune comorbidities in MS patients treated with IFNbeta than in those treated with GA. There have been reports of individual cases of exacerbation of autoimmune diseases, for example,. The effect of GA on autoimmune conditions comorbid to MS has been studied in experimental animal models.
GA has been found to alter the clinical course of type 1 diabetes in animal models,50 and has exerted beneficial effects on uveoretinitis in rodents51, but it had no effect in rodent models of systemic lupus erythematosus (SLE), 52 and was found to aggravate RA, 53 These varying results in animal models suggest that GA may exert its immunomodulatory effect in an antigen-independent manner. As mentioned above, IFN therapy can precipitate immune-mediated abnormalities or exacerbate an existing autoimmune trend. Following reports of autoimmune thyroid and liver disorders in two patients with MS treated with IFN,54, thyroid and liver function and the serum level of 12 autoantibodies against organ-specific (thyroid, gastric, pancreatic) and non-organ-specific antigens were serially monitored. Unlike control patients, autoantibodies (antinuclear, antimuscular, smooth antimuscular, or antithyroid antigens) were detected in 13 patients treated with IFN and, in many cases, were associated with impaired thyroid or liver function.
55 In a separate study of MS patients treated with IFN, serum antimicrosomal and antithymocytic globulin autoantibodies were detected, and a case of autoimmune hepatitis was reported, 56 Summary and future instructions: morbidities are an important component of the range of comorbid conditions seen in MS and contribute to the significant burden of disease suffered by many patients with multiple sclerosis. Autoimmune comorbidities are often associated with MS and can worsen the impact of the disease. These conditions must be treated and treated by neurologists and specialized MS nurses in collaboration with other specialists. It is important to note that the predisposition of MS patients to autoimmune comorbidities is not uniform across diseases.
More studies are needed to establish which genetic and environmental factors influence autoimmune comorbidities in MS. More standardized methods are needed to measure and analyze autoimmune comorbidities and their associations with MS. More studies are also needed to address the effects of autoimmune comorbidities in MS. These future studies should evaluate a wider range of comorbidities and examine how the frequency of comorbidities changes over time.
Finally, the effects of MS treatments on autoimmune comorbidities can influence decisions about therapeutic regimens, and more research is needed in this area. Get the latest clinical knowledge from TouchNeurology. Multiple sclerosis is considered an immune-mediated disease. This means that in multiple sclerosis, the body's immune system attacks the central nervous system.
Most MS experts believe that it is an autoimmune disease, although specific antigens (proteins that boost the immune system) have not been identified in MS. The signs and symptoms of multiple sclerosis can vary widely from person to person and throughout the disease, depending on the location of the affected nerve fibers. Wootla is supported by a collaborative research award on multiple sclerosis from the National Multiple Sclerosis Society. Demyelination is partly the result of the direct destruction of oligodendrocytes by the virus, but it is also a consequence of immune and inflammatory responses.
Perforin mediates axonal transection in multiple sclerosis (MS) and correlates with neurological disability. Vitamin D and its biologically active metabolite, 1,25-dihydroxyvitamin D3 (1,25 (OH), 2D, not only play an important role in regulating calcium and phosphorus homeostasis, but are also an important modulator of immune function. Multiple sclerosis is a disorder in which the body's immune system attacks the protective covering of nerve cells in the brain, optic nerve and spinal cord, called the myelin sheath. Multiple sclerosis (MS) is a potentially disabling disease of the brain and spinal cord (central nervous system).
Tables 2 and 3 show that there are more reported cases of autoimmune comorbidities in MS patients treated with IFNbeta than in those treated with GA. An MRI looks for evidence of injuries (damaged areas) in the brain or spinal cord that indicate multiple sclerosis. Multiple sclerosis as an autoimmune disease The most accepted hypothesis for the pathogenesis of MS is that it is a primary autoimmune disease. .
