Iron Metabolism Pattern And Its Association With Clinical Features In Myasthenia Gravis Patients

PART 1 Iron Metabolism Patterns in Non-anemic Myasthenia Gravis:A Cross-sectional and Follow-up StudyIntroduction:Iron metabolism in myasthenia gravis(MG)and factors associated with it are explored by few published studies.Therefore,this study aimed to compare iron metabolism patterns between patients with MG and healthy individuals as well as between the same group of patients before and after immunotherapy,and to identify predictors of iron metabolism disorders in MG.Materials and methods:For this study,105 patients and healthy individuals were included at baseline,after which paired parametric and non-parametric tests were adopted to compare their iron metabolism patterns,and multivariate binary logistic regression was used to identify predictors of iron metabolism disorders.Patients with MG were then followed up for 12±3 months to explore alterations in their iron metabolism patterns after starting immunotherapy with the help of paired tests.Results:Non-anemic immunotherapy-naive patients with MG had similar hemoglobin,transferrin,and total iron binding capacity levels compared with healthy individuals.However,these MG patients had significantly lower serum iron(SI)and transferrin saturation(TS)levels than healthy individuals.Premenopausal female was significantly associated with SI<65 μg/dL and iron deficiency in these patients.However,iron metabolism parameters did not significantly alter after around 12 ± 3 months of immunotherapy in patients with MG.Conclusion:Iron metabolism disorder was present in patients with MG.Premenopausal female was significantly associated with low SI and iron deficiency.Iron metabolism patterns of MG patients hardly improved after immunotherapy.Given the significant role of iron in human body,it should be given more attention in patients with MG.PART 2 The Association of Iron Metabolism and Clinical Characteristics in Non-anemic Myasthenia Gravis:A Cohort StudyIntroduction:The association of iron metabolism parameters with disease severity and outcome in myasthenia gravis(MG)patients has not been reported.This study was conducted to determined clinical factors including iron metabolism parameters correlated with disease severity and future outcome in non-anemic immunotherapy-na?ve MG patients first receiving immunotherapy.Materials and methods:One hundred and ten immunotherapy-naive MG patients who did not reach minimal manifestation status(MMS)were included in this study.At baseline,univariate and multivariate logistic regression was used to explore independent factors associated with disease severity represented by variables derived from MG activities of daily living score.Immunotherapy was initiated in 106 of these patients,after which 103 and 98 patients remained in the cohort at 6-month and 12-month followup respectively.Univariate and multivariate survival analysis was used to identify independent predictors for MMS in MG patients first receiving immunotherapy.Sensitivity analysis was finally used to validate the results yielded by survival analysis.Results:Higher ferritin level was independently associated with higher risk of severe generalized disease in non-anemic immunotherapy-naive MG patients.Total iron binding capacity<250 μg/dL and the interval between symptom onset and immunotherapy<1 year were independent predictors for MMS at 6-month and 12-month follow-up after initiating immunotherapy.Transferrin<2.00 g/L was an independent predictor for MMS at 12-month follow-up.The results did not change after including patients who were lost or had insufficient follow-up time in the sensitivity analysis.Conclusion:In immunotherapy-na?ve MG patients,ferritin was an indicator for disease severity,while total iron binding capacity and transferrin predicted outcome.Iron metabolism parameters might be promising biomarkers for evaluating disease severity,predicting long-term prognosis,and guiding therapeutic decision in MG patients.PART 3 Clinical and Iron Metabolism Characteristics of Myasthenia Gravis Comorbid with AnemiaIntroduction:Studies on myasthenia gravis(MG)with anemia are rare.The aim of this study is to explore the clinical and iron metabolism characteristics of anemic MG,and compare them with MG without anemia,so as to contribute to management and further research on anemic MG.Materials and methods:This study included 8 anemic and 98 non-anemic MG patients who started immunotherapy at our institution.Clinical and iron metabolism characteristics of anemic MG were described and causes of anemia were analyzed.Parametric,non-parametric,or chi-square tests were used to compare the clinical and iron metabolism characteristics of MG patients with and without anemia.Results:Among the 8 anemia MG patients,5 were premenopausal females and 3 males,5 had iron deficiency anemia and 3 possibly anemia of chronic disease.Serum iron and transferrin saturation levels of anemic MG patients were significantly lower than those of non-anemic ones,but there were no significant differences in transferrin,total iron binding capacity,and ferritin levels between the two groups.Compared with non-anemic MG patients,anemic ones had higher MG activities of daily living scores at inclusion,as well as a larger proportion of premenopausal women,severe generalized disease,and tacrolimus exposure.A larger rate of anemic MG suffered bulbar symptoms at inclusion,which,however,was not statistically significant.Conclusion:Anemic MG patients tended to be premenopausal women and to have iron deficiency anemia.Anemic MG had more significant iron deficiency,more severe symptoms,and higher rates of tacrolimus use.It is necessary to pay more attention to the management of MG with anemia.