Patients with myasthenia gravis (MG) with concurrent chronic lymphocytic leukemia (CLL), or its precursor monoclonal B-cell lymphocytosis (MBL), do not appear to have a direct causal link between each other, according to a study published in Neurology: Neuroimmunology & Neuroinflammation.

In the study, a direct causal link could not be found between the specificities of the monoclonal CLL-phenotype B-cells involved in the CLL and MBL patients and the autoantigens involved in the autoimmune MG also found in those patients, the researchers noted. The B-cell receptors (BCRs) isolated from 2 patients with MG-MBL and 1 patient with MG-CLL displayed no reactivity to recombinant human acetylcholine receptors (AChRs), they added.

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The reactivity of the BCRs was also tested for more general reactivity to neuromuscular components. The BCRs displayed no reaction to murine neuromuscular endplates of tibialis anterior. In a microarray test to assess reactivity to 128 autoantigens, the BCRs only showed weak reactivity to recombinant monoclonal antibodies (mAbs) against collagen VI and insulin.

“In this case series, we demonstrate the absence of a direct causal link between the specificities of the monoclonal CLL phenotype B cells and autoantigens involved in MG, similar to what has been described for CLL-associated autoimmune hemolytic anemia,” the authors said.

To find patients with co-occurring MG and CLL or MBL, a computational immune cell screen of peripheral blood and serum samples collected from 38 patients with MG who were positive for AChR antibodies and 21 age- and sex-matched healthy donors were analyzed.

A total of 5 of the patients with MG and none of the healthy controls displayed a CLL-like B-cell phenotype. Follow-up hematologic flow cytometry revealed that 2 of the 5 patients with MG had MBL. Another patient with AChR-positive MG and CLL also presented at the clinic and was analyzed along with the 2 patients with MG-MBL.

The patient with MG-CLL  was treated with 4 cycles of the anti-CD20 therapy, obinutuzumab, plus chlorambucil. After the 4 cycles, his CLL was in remission, and his ocular MG symptoms had improved and only required low-dose pyridostigmine.


Ingelfinger F, Kramer M, Lutz M, et al. Antibodies produced by CLL phenotype B cells in patients with myasthenia gravis are not directed against neuromuscular endplates. Neurol Neuroimmunol Neuroinflamm. Published online February 8, 2023. doi:10.1212/NXI.0000000000200087