Anti-acetylcholine receptor blocking antibodies in an Argentinian myasthenia gravis cohort

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

Congreso; LXXI Reunión Anual de la Sociedad Argentina de Inmunología; 2023

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies that can recognise several proteins present in the neuromuscular junction, being the anti-acetylcholine receptor autoantibodies (ACRA) the most frequent. There are three types of ACRA, according to their pathogenic mechanisms: binding, modulating and blocking autoantibodies. Blocking antibodies (bACRA) are directed to the acetylcholine binding site, interfering directly with the normal signalling. Unlike binding (biACRA), its role in the disease remains unclear and controversial. In this study, we aim to assess its prevalence and involvement in the pathology of an Argentinian MG cohort.Serum and plasma samples were obtained from 82 MG patients from April 2016 to September 2022. biACRA and bACRA were measured in serum by RIA. Additionally, complement components C3, C4 (RID) and C5a (ELISA) were determined. The severity of the disease was established through ADL and MGC clinical scores. T-test or Mann Whitney test were applied for comparison between means or medians, respectively, while Pearson or Spearman r tests were used for correlation analysis; Fisher’s exact test was conducted for contingency tables.41 (50.0%) MG patients tested positive for bACRA. When comparing complement factors between bACRA positive and bACRA negative populations, we found a statistically significant (ss) difference in the mean value of C4 (25.4 mg/dL and 20.5 mg/dL, respectively) (p=0.006) and the median value of C5a (14.7 ng/mL and 20.8 ng/mL, respectively) (p=0.043), and also a positive correlation between C4 and bACRA titre, which altogether could indicate a minor consumption of complement in the positive group. No ss differences were observed when comparing ADL, MGC and biACRA titre among groups. Focusing only in the bACRA positive group, both ADL and MGC scores correlated inversely with its titre (p=0.0252, r=-0.354; p=0.030, r=-0,3445, respectively). Finally, no association was found within the presence of blocking antibodies and exacerbations of the disease, nor ss correlations between biACRA titre and bACRA titre in the overall population studied.In conclusion, this is the first report of bACRA prevalence in Argentinian MG patients. Overall, we could not find an association with the severity of the disease, although in the bACRA positive individuals an inverse correlation with the clinical scores was observed. Further studies are necessary to determine the importance of bACRA measurement in the diagnosis of MG.