Tonsillar IgA1 as a possible source of hypoglycosylated IgA1 in the serum of IgA nephropathy patients

Abstract

Background. There are many reports of incompletely glycosylated O-linked oligosaccharides on the IgA1 hinge region in certain IgA nephropathy patients. In addition, other reports have noted a relationship between tonsillectomy and IgA nephropathy. Methods. Immunoglobulins from extracts of tonsillectomized tissue and other sources were analysed by isoelectric focusing (IEF) and by enzyme-linked immunosorbent assay (ELISA). Results. The IEF profile of tonsillar IgA differed from that of serum IgA and it was enriched in cationic IgA. However, extracts from tonsillitis controls and IgA nephropathy patients exhibited profiles that were very similar. Enzymatic removal of sialic acid induced a shift of the peaks to the cathode side. The profiles of IgA from treated tonsillar extract and treated serum were closely overlapped. In addition, asialo Galβ1, 3GaINAc was clearly present in cationic IgA from tonsillar extract and in aberrant IgA1 from serum following enzymatic transfer of sialic acid to IgA1. Serum IgA also contained partly sialylated IgA1. Quantitative analysis of IgA and IgG in the extracts indicated that IgA was significantly higher, whereas IgG was significantly lower in IgA nephropathy patients. Conclusions. We found that the IgA1 produced in tonsillar tissue differed from serum IgA1. Furthermore, an overproduction of asialo IgA1 resulted from the disordered balance between IgA- and IgG-producing cells in the tonsils from the IgA nephropathy patient. Although it is unclear how such asialo IgA1 molecules are transferred from tonsil tissue to serum, a tonsillar source may produce a few micrograms of aberrant IgA1 that then appears in serum.