Low expression of complement regulator proteins in myasthenia gravis patients

JUSTO, ME; AGUIRRE, F; LEONI, J; VILLA, A; PAZ, ML

Congreso; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 2022

Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disease that affects the neuromuscular junction. These autoantibodies, mainly directed against the acetylcholine receptor, can activate the classical pathway of the complement system, leading to the destruction of the muscle fiber. Complement is a cascade system which comprises over 50 proteins, many of them involved in the inhibitory regulation of the activation sequence. Different complement regulator proteins (CRPs) have been evaluated in animal models, but little has been examined in MG patients.We measured CD59, CD46 and CD55 expression, three membrane-bound CRPs, on white blood cells (WBCs) from 6 MG patients and 6 healthy controls (HCs). Blood samples were collected in heparinized tubes and processed 24h later. Isolated WBCs were incubated with anti CD59-FITC, CD55-APC and CD46-PE monoclonal antibodies during 30min at RT. Expression of the three markers was analysed by flow cytometry on whole WBCs and on the granulocyte’s subpopulation (the most abundant population and the one with the higher expression of CRPs). Additionally, the severity of the disease was determined and registered through ADL and MGC clinical scores.We found a lower mean fluorescence intensity (MFI) on granulocytes for the three CRPs in MG patients compared to HCs. Only CD46 expression (MFI) showed a statistically significant (ss) difference with HCs (MG: 5796 ± 1507 vs. HCs: 7822 ± 1302, p=0.03). No differences were observed when analysing the whole WBCs’ population. Preliminary, with this initial small and heterogeneous group of patients, we couldn’t find a correlation between CRPs expression and MG severity. In conclusion, this study suggests that a diminished expression of these three CRPs, especially CD46, might be involved in a higher susceptibility to complement damage in MG patients, although further studies involving a higher number of participants are needed.