Correlation Between Serum Anti-desmoglein Antibodies' Subclasses And High Antibody Titers Of Pemphigus In Remission

Objective:Pemphigus is an autoimmune bullous skin disease that can seriously endanger human health.Serum anti-desmoglein(Dsg)antibody levels are often used to diagnose the type of pemphigus,monitor the patient's severity,and evaluate their prognosis.However,in clinical practice,it has been found that some pemphigus patients in remission have high antibody titers,which also brings a great challenge to the adjustment of their therapeutic regimens.Because the first-line treatment of pemphigus is systemic corticosteroids,and the timely reduction of the corticosteroids‘dosage can minimize the adverse effects.Therefore,for such patients,it is very important to find indicators that can accurately assess their condition and prognosis.Recently,the antibody subclasses which bind to the conformational epitopes of Dsg have been found to be pathogenic antibodies.At the same time,anti-Dsg IgG4 is dominant during active disease while anti-Dsg IgG1 is dominant during remission.Determining the levels of pathogenic conformational antibodies and anti-Dsg IgG1/4 helps better assess patients's severity and judge the probability of recurrence,thereby improving the clinical diagnosis and treatment of pemphigus.This reasearch intends to analyze the relationship between levels of anti-Dsg antibodies'subclasses and patients' disease severity and prognosis to provide a reference for the diagnosis and treatment of pemphigus.Methods:The clinical data of 134 pemphigus patients who were diagnosed and treated in Department of Dermatology,Peking Union Medical College Hospital from January 2013 to September 2020 were retrospectively analyzed.Eligible ordinary pemphigus patients(control group)and pemphigus patients with high antibody titers in remission(experimental group)were included,and their clinical data were collected and analyzed.Collect serum samples of the control group during active disease and remission,and serum samples of the experimental group during remission.The levels of anti Dsg-1/3 antibodies,anti Dsg-1/3 IgG1/4,and conformational anti Dsg-1/3 IgG1/4 of the above-mentioned serum samples were detected.Analyze the relationship between levels of serum antibodies and each subclass and patients' condition(active/remission)to determine whether there are certain antibody subclasses significantly related to patients' disease severity.Analyze the relationship between leves of serum antibodies and each subclass of the control group in remission and their prognosis(relapse or not during follow-up)to determine whether there are certain antibody subclasses significantly affecting patients's recurrence-free survival time.Results:1.Compared with active phase,non-conformational anti Dsg-1/3 IgG1's proportion of the control group was significantly increased in remission.Non-conformational anti Dsg-1 IgG1's proportion of the experimental group was significantly lower than the control group.2.Compared with active phase,non-conformational anti Dsg-1 IgG4's proportion of the control group decreased significantly in remission.3.In the control group,the IgG4/IgG1 ratio of the anti Dsg-1/3 antibodies decreased significantly in remission.4.Among patients with positive anti Dsg-1 antibodies,high level of non-conformational anti Dsg-1 IgG4 was a prognostic risk factor.Among patients with positive anti Dsg-3 antibodies,only in univariate analysis,it was found high level of non-conformational anti Dsg-3 IgG1 might be a prognostic risk factor(P=0.103).Conclusions:1.In patients with positive anti Dsg-1 antibodies,levels of total anti Dsg-1 antibody and anti Dsg-1 IgG4 were positively correlated with disease severity while non-conformational anti Dsg-1 IgG4 was negatively correlated with it.High level of non-conformational anti Dsg-1 IgG4 was a risk factor of pemphigus patients' prognosis.2.In patients with positive anti Dsg-3 antibodies,the level of total anti Dsg-3 antibody was positively correlated with disease severity,while anti Dsg-3 IgG4's level was negatively correlated with it.The levels of anti Dsg-3 antibody and each subclass had no significant effect on the prognosis of pemphigus.