In SLE, various autoantibodies can be positive, including ANA, anti-dsDNA antibody, anti-Sm antibody, anti-RNP antibody, anti-Ro/SS-A antibody, and anti-La/SS-B antibody. Among them, anti-ds DNA antibody is most commonly associated with lupus nephritis (LN), and the antibody titer is usually correlated with disease activity (11). Anti-Sm antibody has also been reported to show a close relation with renal disease, and this association is stronger when anti-Sm antibody is positive together with anti-dsDNA antibody (12). Anti-RNP antibody is detected in 25–47% of SLE patients, with high anti-RNP antibody titers being diagnostic of MCTD. Both anti-Sm and anti-RNP antibodies are more important for diagnosis of SLE than for monitoring disease progression, although anti-RNP antibody shows a higher prevalence in patients with Raynaud's phenomenon and is associated with milder renal involvement, while anti-Sm antibody reflects the severity and of renal involvement and renal disease activity (2). Kitridou et al. performed renal biopsy in 10 MCTD patients with renal disease, and reported that six patients (60%) had membranous nephropathy, two (20%) had mesangial glomerulonephritis, one (10%) had local sclerosing glomerulonephritis, and one (10%) had membranoproliferative nephritis (3). In addition, Bennet et al. performed renal biopsy in four of 20 patients with MCTD, and found that three patients had membranous glomerulonephritis (13) .
In SLE, overproduction of type I interferons (IFNs) and autoantibodies targeting nucleic acids has been reported (14). Kirou et al. suggested that activation of the IFN pathway defines a subgroup of SLE patients whose have more severe disease, including more severe renal disease, and increased disease activity, which is reflected by activation of complement and the presence of autoantibodies targeting RNA binding proteins (RBP), i.e., antibodies specific for Ro, U1 RNP, and Sm (15). Lövgren et al. reported that the induction of IFN production by SLE serum was associated with the presence of anti-RBP antibodies with or without anti-DNA antibodies, but not with anti-DNA antibodies alone (16) .
Two distinct mechanisms for the formation of immune deposits in glomerulonephritis have been suggested, which are passive trapping of immune complexes associated with mesangial or subendothelial deposits, or in situ formation of immune complexes at subepithelial, subendothelial, and mesangial sites (17). The latter mechanism might be considered in MCTD patients with concomitant membranous nephropathy because they predominantly have subepithelial deposits. However, the precise immunological processes underlying membranous nephropathy in MCTD patients are still unclear.
In conclusion, the present study indicated that 5 patients out of 10 patients with anti-RNP antibody positivity only showed MN and normocomplementemia. On the other hand, in patients who are positive for both anti-Sm antibody and anti-RNP antibody, the main renal disease is MES with hypocomplementemia. Among patients showing positivity for anti-RNP antibody alone, those with MCTD seem likely to develop pure MN, while those with SLE tend to have MES as well as MN.