AUTHOR=Chen Yuping , Tao Xiaoyong , Wang Yan , Xu Shengjie , Yang Yanhua , Han Jinming , Qiu Feng 

TITLE=Clinical Characteristics and Prognosis of Anti-AChR Positive Myasthenia Gravis Combined With Anti-LRP4 or Anti-Titin Antibody

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.873599

DOI=10.3389/fneur.2022.873599

ISSN=1664-2295

ABSTRACT=Objective: To summarize the clinical characteristics and prognosis of anti- acetylcholine receptor (AChR) positive myasthenia gravis (MG) patients with a combination of anti-LRP4 or Titin antibodies. 
Methods: A total of 188 patients with generalized MG before immunotherapy were retrospectively collected and then divided into three groups: single anti-AChR positive-MG (AChR-MG, 101 cases), anti-AChR combined with anti-low-density lipoprotein receptor-related protein 4-positive MG (AChR+LRP4-MG, 29 cases) and anti-AChR combined with anti-Titin-positive MG (AChR+Titin-MG, 58 cases). Clinical manifestations, therapeutic responses to immunotherapy, and follow-up information were analyzed.
Results: Of the 188 seropositive MG patients, 29 (15.4%) were positive for both AChR and LRP4 antibodies, and 58 (30.9%) were positive for both AChR and Titin antibodies. The mean disease onset ages in the three groups were 47.4±17.0, 49.8±19.2, and 48.1±16.5 years, respectively. AChR+LRP4-MG showed female predominance (27.6% were males and 72.4% were females), with mild overall clinical symptoms. The AChR+Titin-MG group showed shorter times for conversion to generalized MG (5.1±4.0 months) than the AChR-MG group (11.6±9.0 months) and the AChR+LRP4-MG group (13.0±8.5 months; P<0.001 in both cases). Furthermore, AChR+Titin-MG group had increased bulbar dysfunction, higher incidences of thymoma (32.8% vs 19.8% and 3.4%, P=0.035), more severe quantitative MG scores, as assessed by both QMG scores [15.5 (11.75-22.5) vs. 13 (8-19), P=0.005; and 9 (6-14) P<0.001], and MG-ADL scores [10 (8-13) vs. 8 (5-13), P=0.018; and 6 (4-8), P<0.001]. Treatment for AChR+Titin-MG was largely dependent on corticosteroids and immunosuppressive agents (56.7% vs 19.2% and 16.7%, p=0.028). The rates of achieving minimal manifestations status (MMS) or better within 2 years following immunotherapy in the three groups were 51.5%, 62.1%, and 51.7%, respectively (P = 0.581).
Conclusion: Clinical symptoms of anti-AChR positive MG combined with Titin antibody were more severe and progressed faster than those in the AChR + LRP4 and AChR groups. Regardless of antibody status, all patients responded well to immunotherapy and had relatively good prognoses.