Immune Mechanisms Of Neutropenia With Graves’ Disease

Graves’ disease(GD) is one of the most common organ-specificautoimmune diseases, and immune factors play a great role in itspathogenesis although it remains not completely clear. Under pathogenicstatus, a breakdown in the tolerance of self antigen and different subsets ofT and B cells as well as their regulatory populations play important roles inthe occurrence and maintenance of the disease process. Th17cells, a newlyidentified effector T-cell subset, have recently been shown to play a role inGraves’ disease, mainly related to the intractable GD.Neutropenia which is defined as circulating neutrophil number less than2000/μl, can be coexistent with Graves’ disease in some patients.Mild andmoderate neutropenia can be seen in patients with untreated Graves’ disease,there were some findings suggest an immune basis for the association of GDwith neutropenia. Circulating autoantibodies specific for TSHR withopsonic activity against homologous neutrophils were found in50%of GDpationts. Cell-bound IgG was observed on autologous cells of in more GDpatients but another research indicated that those IgG are not antineutrophilautoantibodies, but possibly immune complexes bind to neutrophils.Researchers in China have found the systemic immunity turbulence insideGD patients is associated with neutropenia,howerver the exact mechanismremain unkonwn.The mechanisms for ATD-induced neutropenia are complicated, andmany hypotheses have been presented which maily recognized asimmunological reactions induced by drugs. Some studies suggest the ATD-dependent neutrophil-specific IgG and IgM which may play aopsonizing role or through a complement-dependent way in inducingneutropenia. The antibodies can sometimes combined with myeloidprecursors and cause bone marrow hypoplasia. The production of theseantibodies are possibly due to the new neoantigens formed by ATD ormetabolite and cell membrane components. T cellular immune mechanismsmay play a role in ATD-induced neutropenia although this is stillunclear.Moreover, ANCA positivity are developed in some patients withGraves’ disease especially with PTU treatment and are strongly associatedwith ATD-induced vasculitis. Recent years,there are also cases of ANCAimplicated in the ATD-induced neutropenia reported.One in vitroexperimental study have demonstrated the pathogenic role of ANCA forneutrophils through a complement-dependent way, and further studies areneeded to clarify this idea.