Multiple sclerosis (MS) is one of the most common central nervous system autoimmune diseases. The diagnosis is based on the 2017 McDonald criteria, which allows for early diagnosis; however, this should be made only if there is no better explanation for the existing symptoms [1]. The term “no better explanation” is vague since there is no clear diagnostic test for excluding alternative diagnoses. However, abnormal lab results should serve as “a red flag.” To this effect, necessary laboratory tests include cell blood count, liver and kidney function test, thyroid function, ANA, vitamin B12, folate, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). However, these may vary across centers depending on availability and cost [2].
There are plenty of potential alternatives that can act as a mimic for MS. There is no clear guideline for excluding alternative diagnoses, which is usually left to the judgment of the treating physician. Evidence for systemic autoimmune disease with respect to MS is usually searched to exclude possible alternative diagnoses, including systemic lupus erythematosus (SLE) and Sjogren’s syndrome. Further, examination for antinuclear autoimmune antibody (ANA), an autoantibody group against nuclear and cellular antigens, is a common practice. These antibodies are often indicative of immune dysregulation [3]. However, not all ANA-positive results are clinically meaningful or a cause of concern. These antibodies react with > 150 nuclear antigens and are not all associated with known autoimmune diseases [4]. ANA is a commonly ordered test with respect to suspected autoimmune diseases, including SLE and other rheumatological diseases. The ANA test is sensitive but nonspecific for SLE diagnosis since ANA can be found in different types of autoimmune diseases, including scleroderma and Sjogren’s syndrome, as well as occasionally in healthy individuals [5].
Clinicians frequently order tests for serum autoantibodies, especially ANA, because some rheumatological diseases can present with neurological symptoms resembeling MS. However, ANA testing is generally considered to have a low-positive predictive value [6]. The significance of ANA testing in patients with MS remains unclear. There have been limited studies on the association between MS and ANA with most being performed before the introduction of the 2000 McDonald criteria for MS diagnosis. A previous study was conducted before 2000 to examine whether patients with MS who were ANA positive should be excluded from clinical trials and reported no difference between patients with MS with low ANA titer and those that were ANA negative [7]. A recent study tried to look at the prevalence of positive autoantibodies in patient with MS in Vienna and reported 18% of the patients with MS had positive autoantibody without having another autoimmune disease [8]. However, these findings could not be generalized in different cohorts with different ethnic characteristics and prevalence of MS and other autoimmune diseases.
The specific ANA value in MS diagnosis remains unclear; however, an increased level should be indicative of an alternative diagnosis. Previous studies have reported an incidence of positive ANA in patients with MS ranging from 2 to 44% [9]. The correlation between ANA titer and the disability extent remains unclear. This study aimed to compare the prevalence of positive ANA antibody and its titer between patients with MS and patients with general neurological diseases in Saudi Arabia. Further, we aimed to examine the association between the ANA level and disease disability by measuring the Expanded Disability Status Score (EDSS).