Pathogenesis, Clinical Presentations and Diagnosis of IgG4-related Disease: AReview

Abstract

IgG4-Related Disease (IgG4RD) was identified by the International Classification of
Diseases (ICD) in 2012. Numerous diseases, including Mikulicz’s disease, Kuttner’s
tumor, Riedel’s thyroiditis, and Ormond’s disease, are pathologically associated
with IgG4. Here, we present a review of the clinical presentation and pathogenesis
of IgG4-associated disease. IgG4-RD term has been used to refer to a group of
diseases involving multiple organs in which there is an abundant IgG4-positive
lymphoplasmacytic infiltration, storiform fibrosis, obliterative phlebitis, and mild
to moderate tissue eosinophilia, all of which show clinically as a tumefactive lesion,
usually in more than one organ. IgG4 exhibits a unique property called an unstable
disulfide bond between its heavy chain, as described by Fab-arm exchange which
enables the recombination of a single IgG4 heavy chain with other IgG4 heavy
chains, resulting in a bispecific antibody incapable of cross-linking and thus of
forming an immune complex. IgG4-RD pathomechanism that causes serum IgG4
increase and tissue IgG4-plasma-cell deposition that is pathogenic, rather than the
IgG4 itself. Genetic predisposition, autoimmunity, T-cell dysregulation, infection,
and dysbiosis are just a few of the underlying pathomechanisms. Clinical
symptoms are also frequently complex and may involve many organs. Confirmation
of a diagnosis required a comprehensive anamnesis and examination.