Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis.

Myasthenia Gravis (MG) is an autoimmune disease associated with severe neuromuscular weakness. Diagnostic confirmation of MG is typically delayed and secured in about 85% and 50% of patients with generalized and ocular MG, respectively with serum antibodies. We have identified a sensitive and specific diagnostic biomarker for various MG serotypes with quantitative proteomics. Serum proteomes of 18 individuals (MG patients, healthy controls (HC), Rheumatoid Arthritis (RA) were quantified in a pilot study and occurrence of high residual fibrinogen was validated by immunoblotting and further investigated by targeted mass spectrometry on the sera of 79 individuals (31 MG of various serotypes, 30 HC, 18 RA). Initial proteomic analysis identified high residual fibrinogen in MG patient sera which was then validated by antibody-based testing. Subsequently, a blinded study of independent samples showed 100% differentiation of MG patients from controls. A final serological quantification of 14 surrogate peptides derived from α-, ß-, and γ-subunits of fibrinogen in 79 individuals revealed fibrinogen to be highly specific and 100% sensitive for MG (p < 0.00001), with a remarkable average higher abundance of > 1000-fold over control groups. Our unanticipated discovery of high levels of residual serum fibrinogen in all MG patients can secure rapid bedside diagnosis of MG.

Rituximab in Myasthenia Gravis - Where do we stand?

Introduction: Myasthenia gravis (MG) is an antibody-mediated disease with diverse serology and clinical presentation. Currently, MG is managed by untargeted immunomodulatory agents. About 15% patients are refractory to these therapies. Several novel and targeted treatments are on the horizon. Rituximab, a monoclonal antibody, is reported to be highly effective with widespread oof-label usage in MG, particularly in patients with antibody against muscle-specific kinase or refractory disease. However, a recent trial showed negative results. Compared to conventional oral immunosuppressive therapies used in MG, Rituximab has several benefits. Regular hematological monitoring is not required though serious side effects can occur. Current status of Rituximab in MG and newer immunosuppressants is discussed.Areas explored: Biologic features, clinical effectiveness, safety profile, and newer preparations of Rituximab.Expert opinion: Rituximab provides a promising option for management of MG, particularly in patients with muscle-specific kinase antibodies or those with refractory disease. Several knowledge gaps remain due to scarcity of data from randomized controlled studies. Despite lack of regulatory approval Rituximab has found widespread usage in MG. Large, well-designed studies are needed to assess the comparative efficacy of Rituximab and its optimal regimen in MG.