The Role of Osteopontin and Its Gene on Glucocorticoid Response in Myasthenia Gravis

Abstract

Biomarkers that assess treatment response for patients with the autoimmune disorder, myasthenia gravis (MG), have not been evaluated to a significant extent. We hypothesized the pro-inflammatory cytokine, osteopontin (OPN), may be associated with variability of response to glucocorticoids (GCs) in patients with MG. A cohort of 250 MG patients treated with standardized protocol of GCs was recruited, and plasma OPN and polymorphisms of its gene, secreted phosphoprotein 1 (SPP1), were evaluated. Mean OPN levels were higher in patients compared to healthy controls. Carriers of rs11728697*T allele (allele definition: one of two or more alternative forms of a gene) were more frequent in the poorly GC responsive group compared to the GC responsive group indicating an association of rs11728697*T allele with GC non-responsiveness. One risk haplotype (AGTACT) was identified associated with GC non-responsiveness compared with GC responsive MG group. Genetic variations of SPP1 were found associated with the response to GC among MG patients.

Understanding the burden of refractory myasthenia gravis

“…9,25 At present, although certain patient and clinical characteristics have been associated with an increased risk of being refractory to treatment, there are no reliable biomarkers to determine, early on, which patients will respond to therapy. Patients with anti-MuSK antibody-positive MG are unlikely to respond to AChE inhibitors 94 and there is some evidence that genetic associations might explain the variability of the response to drugs, including glucocorticoids and azathioprine, among patients with MG. [95][96][97] Further work in this area may help to predict which patients will have disease that is refractory to treatment or experience intolerable AEs to certain drugs in clinical practice. Refractory MG is uncommon, even in tertiary clinical centers.…”

Comparative study of computed tomography of normal and lymphoid follicular hyperplasia thymus in myasthenia gravis patients

“…LFH, also known as autoimmune thymitis, is characterized by a normal size and weight of the thymus with chronic inflammation and proliferation of lymphoid follicles, active germinal centers and increased numbers of lymphocytes and epithelial cells (23,24). The symptoms of MG, including the impairment of ocular (extra-ocular muscles, eyelids), bulbar (ingestion function, voice/speech function, respiratory function, facial muscles) and limb-axial muscles (arms, legs and neck), always improve after thymectomy in patients with thymoma or LFH thymus (5)(6)(7)(8). Furthermore, in MG patients with LFH, the thymus also frequently appears as atrophic on CT scan and gross examination, particularly in elderly patients.…”

“…An estimated 80-90% of MG patients have thymic abnormalities, of which lymphoid follicular hyperplasia (LFH) accounts for 65-75% (4). Thymectomy has almost always been routinely performed for patients with MG and is effective in most cases of LFH (5)(6)(7)(8). From the position of the thoracic surgeon and under consideration of the cost, pre-operative computed tomography (CT) is a more valuable method than magnetic resonance imaging and 201 Tl-single photon emission CT in diagnosing the abnormalities of thymus, including LFH and thymoma.…”

Advances in autoimmune myasthenia gravis management

“…Also, there is a possibly up to 30 percent of patients being poorly responsive to corticosteroids based on a lack of improvement or intolerance [102–104]. Treatment resistance is likely to be more a function of individual differences in corticosteroid responsiveness than severity of disease per see [103–106]. Corticosteroids impact autoimmune mechanisms in several ways.…”