AChRnegative

AChRnegative is a term used to describe the absence of detectable acetylcholine receptor (AChR) activity or expression in a given context. In clinical neurology, it most often refers to myasthenia gravis (MG) patients who test negative for AChR autoantibodies on standard serologic assays, a group commonly described as seronegative MG. Advances in testing have revealed that many of these patients harbor antibodies against other synaptic proteins, notably MuSK (muscle-specific kinase) or LRP4, leading to refined subtypes such as MuSK-positive MG or LRP4-positive MG. AChRnegative MG typically accounts for a minority of MG cases, with estimates ranging from about 10% to 30% depending on assay sensitivity.

Diagnosis of AChRnegative MG relies on the clinical pattern of fatigable weakness and supportive tests such as electrophysiology (repetitive nerve stimulation or single-fiber EMG) and responsiveness to acetylcholinesterase inhibitors. Serological workup begins with AChR antibody testing; if negative, testing for MuSK and LRP4 antibodies and the use of cell-based assays can identify non-AChR antibodies.

Pathophysiology in AChRnegative MG involves mechanisms distinct from classic AChR-antibody-mediated disruption, including other autoantibody targets and T-cell–mediated processes. Thymic pathology, common in AChR MG, is less consistently associated with seronegative cases, though thymic abnormalities can still be present in some patients.

Treatment is guided by MG subtype and severity and typically includes acetylcholinesterase inhibitors, as well as immunosuppressive therapies when needed. Management aims to improve neuromuscular transmission and quality of life, with thymectomy considered in select MG patients with thymic pathology.

In research and laboratory settings, AChRnegative may also describe tissue or cell samples lacking AChR expression, distinguishing receptor-deficient specimens from normal controls.