Central Nervous System (CNS) and Systemic Autoimmune Disease: Coexistence or More?

Dear Sir,

The central nervous system (CNS) autoimmune and demyelinating diseases have been known to be associated with systemic autoimmune diseases. However, their magnitude of association and the underlying common genetic and/or environmental predisposition is still a subject of ongoing research. The study published by Malli et al.[1] in the current issue emphasizes the need for more hospital- and community-based disease-specific registries to answer this conundrum. The study has specifically looked at primary demyelinating diseases of the CNS and classified patients into multiple sclerosis (MS), anti-aquaporin 4 (AQP4)-positive, anti-myelin oligodendrocyte glycoprotein-positive, and seronegative non-MS cases. They have studied the frequency of concomitant autoimmune disorders, anti-nuclear antibody (ANA), and antithyroid antibody (ATAb) in the cohort Mangalore Demyelinating Disease Registry (MANDDIR).

The association of MS with other autoimmune diseases has been shown in earlier cohorts.[23] The criticism of such associations has been linked to the mere serological association than any clinical implication. Another challenge is that some of the newer treatment modalities, like alemtuzumab, used in MS can itself cause diseases like Goodpasture syndrome and thyroid diseases. Longitudinal studies can answer if there is a mere serological coexistence, and if their early detection would alter the course of the disease by timely intervention. Such registries, as well as population-based data, are available in the developed world,[4] and the contribution of environmental and genetic factors warrant similar studies in the Indian subcontinent. It has been shown that MS patients have an increased risk of rheumatoid arthritis, psoriasis, thyroid diseases, ankylosing spondylitis, dermatomyositis, Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory bowel disease, myasthenia gravis, uveitis, and pemphigoid.[456] There have been very few earlier registry-based data in MS from India.[78] These have shown comparable prevalence and clinical features. Studies have also shown the association of neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) with systemic sclerosis[9] and other systemic connective tissue diseases (CTD).[10] AQP4 antibody was detectable in 78% of the patients with CTD and NMOSD but in none of the patients with CTD and neurological disorders other than NMO, longitudinally extensive transverse myelitis (LETM), or optic neuritis (ON). This strengthens the concept that the AQP4 antibody is responsible for the pathogenesis of these neurological conditions and is not simply a part of a group of antibodies associated with other connective tissue disorders. The current study found ATAb as the commonest association in about a quarter of the patients of MS as well as healthy controls. It is, therefore, imperative that longitudinal cohorts provide associations if any. This would help in channelizing the constrained resources toward the management of clinical problems, rather than advising a ‘panel’ of antibody tests. A positive result would create anxiety and stress for the patients, a challenge for the treating clinician, and would add to the cost of the disease. On the other hand, early detection of another autoimmune disease, which would impact the clinical course, would be empowering the clinician. The detection of the neurological findings in rheumatological diseases has a profound bearing, especially, SLE, sarcoidosis, and Sjögren syndrome, as it warrants aggressive and prolonged immunosuppression.[6] Whether the reverse is true still needs to be explored. As more and more antibodies are added to the list of the ‘autoimmune panel,’ results from registries and population-based studies may provide answers to how much diagnostic cost needs to be added up. This publication from this registry has sown the seed and the preliminary efforts also need to be applauded so that the registry matures and provides more robust results.