Systemic lupus erythematosus patients contain significantly less igm against mono-methylated lysine than healthy subjects.

Post-translational modifications on proteins are important in biological processes but may create neo-epitopes that induce autoimmune responses. In this study, we measured the serum IgG and IgM response to a set of non-modified or acetyl- and methyl-modified peptides corresponding to residues 1-19 of the histone 3 N-terminal tail in systemic lupus erythematosus (SLE) patients and healthy subjects. Our results indicated that the SLE patients and healthy subjects produced antibodies (Abs) to the peptides, but the two groups had different Ab isotype and epitope preferences. Abs to the non-modified form, H31-19, were of the IgG isotype and produced by SLE patients. They could not recognize the scrambled H31-19, which contained the same amino acid composition but a different sequence as H31-19. In comparison, healthy subjects in general did not produce IgG against H31-19. However, about 70% of the healthy subjects produced IgM Abs against mono-methylated K9 of H31-19 (H31-19K9me). Our further studies revealed that ε-amine mono-methylated lysine could completely inhibit the IgM binding to H31-19K9me, but lysine had no inhibitory effect. In addition, the IgM Abs could bind peptides containing a mono-methylated lysine residue but with totally different sequences. Thus, mono-methylated lysine was the sole epitope for the IgM. Interestingly, SLE patients had much lower levels of this type of IgM. There was no obvious correlation between the IgM levels and disease activity and the decreased IgM was unlikely caused by medical treatments.We also found that the IgM Abs were not polyreactive to dsDNA, ssDNA, lipopolysaccharide (LPS) or insulin and they did not exist in umbilical cord serum, implying that they were not natural Abs. The IgM Abs against mono-methylated lysine are present in healthy subjects but are significantly lower in SLE patients, suggesting a distinct origin of production and special physiological functions.

Cytoplasmic domain of human Fcalpha/mu receptor is required for ligand internalization.

The Fcalpha/mu receptor (Fcalpha/microR), a type I transmembrane protein, is an immunoglobulin Fc receptor for both IgA and IgM. Its functions in immune defense are not clear at present. In this work, human Fcalpha/microR was expressed in CHO, 293T, and COS-7 cells to study its biochemical functions. Fcalpha/microR expressed by CHO and 293T was only in monomer form in cytoplasma and the monomeric receptor could not bind IgA or IgM. In comparison, Fcalpha/microR expressed by COS-7 cells had both monomer and dimer forms. The binding assay showed that Fcalpha/microR expressed by COS-7 cells could bind IgM strongly and IgA weakly, implying that dimeric receptor could be expressed on cell membrane and functioned. The bound IgM could be internalized and the internalization was abolished when the cytoplasmic domain of Fcalpha/microR was truncated. Therefore, the cytoplasmic portion of human Fcalpha/microR is required in the internalization.