Clinical utility of human leukocyte antigen genotyping and immunoglobulin G4 autoantibody testing in autoimmune neurological diseases: A focused minireview

Core Tip

Core Tip: Human leukocyte antigen (HLA) class II molecules present peptides derived from neuronal and glial membrane proteins to CD4+ T cells, particularly follicular helper T cells and interleukin (IL)-10-producing regulatory subsets. In the IL-10-rich milieu associated with chronic antigen exposure, B cells undergo immunoglobulin G4 (IgG4) class switching and differentiate into high-affinity plasma cells and memory cells, thereby driving the production of pathogenic IgG4 neuro-autoantibodies. These antibodies disrupt protein-protein interactions rather than inducing classical inflammatory responses. IgG4 neuro-autoantibodies are mainly detected in serum and cerebrospinal fluid using cell-based assays, although these assays are labor-intensive and require specialized cell culture and transfection facilities. HLA typing may have clinical relevance in patients with intrathecal IgG4 antibodies and may help explain specific phenotypic associations in anti-Ig-like domain-containing protein 5 disease, including the increased frequency of sleep and bulbar manifestations. Distinct HLA associations also underlie the divergent clinical profiles observed in leucine-rich glioma-inactivated 1 and contactin-associated protein-like 2 antibody diseases.