RT Journal Article
SR Electronic
T1 Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e200087
DO 10.1212/NXI.0000000000200087
VO 10
IS 2
A1 Florian Ingelfinger
A1 Michael Kramer
A1 Mirjam Lutz
A1 Corinne C. Widmer
A1 Luca Piccoli
A1 Stefanie Kreutmair
A1 Tobias Wertheimer
A1 Mark Woodhall
A1 Patrick Waters
A1 Federica Sallusto
A1 Antonio Lanzavecchia
A1 Sarah Mundt
A1 Burkhard Becher
A1 Bettina Schreiner
YR 2023
UL http://nn.neurology.org/content/10/2/e200087.abstract
AB Background and Objectives Myasthenia gravis (MG) can in rare cases be an autoimmune phenomenon associated with hematologic malignancies such as chronic lymphocytic leukemia (CLL). It is unclear whether in patients with MG and CLL, the leukemic B cells are the ones directly driving the autoimmune response against neuromuscular endplates.Methods We identified patients with acetylcholine receptor antibody–positive (AChR+) MG and CLL or monoclonal B-cell lymphocytosis (MBL), a precursor to CLL, and described their clinical features, including treatment responses. We generated recombinant monoclonal antibodies (mAbs) corresponding to the B-cell receptors of the CLL phenotype B cells and screened them for autoantigen binding.Results A computational immune cell screen revealed a subgroup of 5/38 patients with MG and 0/21 healthy controls who displayed a CLL-like B-cell phenotype. In follow-up hematologic flow cytometry, 2 of these 5 patients were diagnosed with an MBL. An additional patient with AChR+ MG as a complication of manifest CLL presented at our neuromuscular clinic and was successfully treated with the anti-CD20 therapy obinutuzumab plus chlorambucil. We investigated the specificities of expanding CLL-like B-cell clones to assess a direct causal link between the 2 diseases. However, we observed no reactivity of the clones against the AChR, antigens at the neuromuscular junction, or other common autoantigens.Discussion Our study suggests that AChR autoantibodies are produced by nonmalignant, polyclonal B cells The new anti-CD20 treatment obinutuzumab might be considered in effectively treating AChR+ MG.Classification of Evidence This is a single case study and provides Class IV evidence that obinutuzumab is safe to use in patients with MG.AChR=acetylcholine receptor antibody; BCL=B-cell receptor; CLL=chronic lymphocytic leukemia; mAb=monoclonal antibody; LLN=lower limit of normal; MG=myasthenia gravis; PBMC=peripheral blood mononuclear cell; tSNE=t-distributed stochastic neighbor embedding