Purpose Natural killer cell cytotoxicity is regulated by inhibitory receptors recognising HLA. These include the CD94/NKG2A and the killer cell immunoglobulin-like receptors (KIR). Previously we described functional autoantibodies to CD94/NKG2A, in patients with systemic lupus erythematosus (SLE). Here we investigated whether patients with SLE, primary Sjögren’s syndrome (pSS) or systemic sclerosis (SSc) have autoantibodies to KIR-receptors and whether presence of such autoantibodies correlates to clinical manifestations.
Method HEK293-transfectants expressing KIR2DL1, KIR2DL2, KIR2DL3, KIR3DL1, KIR3DL2, KIR2DL4, KIR2DS2 or KIR2DS4 were incubated with serum from 191 SLE, 121 pSS, 48 SSc patients and 100 healthy donors. Binding of human IgG to each transfectant was determined using flow-cytometry and the median fluorescence intensity (MFI) was divided by the MFI of untransfected cells. The cut-off for autoantibody-positivity was set at the mean +4 standard deviations of healthy donors. Clinical data were tested for association to the presence of anti-KIR autoantibodies using Fischer’s exact test.
Results Autoantibodies to KIR-receptors were identified in 23.0% of SLE, 10.7% of pSS and 12.5% of SSc patients compared to 4.0% of healthy individuals. Anti-KIR antibodies to all eight receptors studied were detected in SLE and pSS sera, whereas SSc sera reacted with four of the receptors. The highest titers of anti-KIR antibodies were found in SLE sera. All KIR-positive healthy donor sera and the majority of KIR-positive pSS (76.9%) and SSc (50.0%) sera reacted with 1 KIR-receptor. In contrast, 36.3% and 22.6% of the anti-KIR-positive SLE sera reacted with 2–3 and >3 KIR-receptors, respectively. Autoantibodies to >3 KIRs were associated with an increased risk for lupus nephritis (80.0% vs 27.2%, p=0.001), an increased number of ACR criteria fulfilled (7 vs 6, p=0.02), presence of anti-Sm (50.0% vs 13.6%, p=0.01) and anti-RNP (70.0% vs 23.1%, p=0.003) antibodies compared to patients without anti-KIR antibodies. Age at disease onset (21 vs 30, p=0.74), SLICC damage index (1.5 vs 1.0, p=0.31) or presence of anti-dsDNA (70.0% vs 60.5%) were not significantly different.
Conclusion Autoantibodies to KIR-receptors are found in patients with SLE, pSS and SSc. Given the association with lupus nephritis such autoantibodies may have a clinical importance.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.