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Background    KIR2DS5  gene encodes an activating natural killer cell receptor whose ligand is not known. It was recently reported to affect the outcome of hematopoietic stem cell transplantation.    Methodology/Principal Findings  In our studies on  KIR2DS5  gene associations with human diseases, we compared the frequencies of this gene in patients and relevant controls. Typing for  KIR2DS5  gene was performed by either individual or multiplex polymerase chain reactions which, when compared in the same samples, gave concordant results. We noted an apparently protective effect of  KIR2DS5  gene presence in several clinical conditions, but not in others. Namely, this effect was observed in ankylosing spondylitis ( p  = 0.003, odds ratio [OR] = 0.47, confidence interval [CI] = 0.28–0.79), endometriosis ( p  = 0.03, OR = 0.25, CI = 0.07–0.82) and acute rejection of kidney graft ( p  = 0.0056, OR = 0.44, CI = 0.24–0.80), but not in non-small-cell lung carcinoma, rheumatoid arthritis, spontaneous abortion, or leukemia (all  p >0.05). In addition, the simultaneous presence of  KIR2DS5  gene and  HLA-C  C1 allotype exhibited an even stronger protective effect on ankylosing spondylitis ( p  = 0.0003, OR = 0.35, CI = 0.19–0.65), whereas a lack of  KIR2DS5  and the presence of the  HLA-C  C2 allotype was associated with ankylosing spondylitis ( p  = 0.0017, OR = 1.92, CI = 1.28–2.89), whereas a lack of KIR2DS5 and presence of C1 allotype was associated with rheumatoid arthritis ( p  = 0.005, OR = 1.47, CI = 1.13–1.92). The presence of both  KIR2DS5  and C1 seemed to protect from acute kidney graft rejection ( p  = 0.017, OR = 0.47, CI = 0.25–0.89), whereas lack of  KIR2DS5  and presence of C2 seemed to favor rejection ( p  = 0.0015, OR = 2.13, CI = 1.34–3.37).    Conclusions/Significance  Our results suggest that KIR2DS5 may protect from endometriosis, ankylosing spondylitis, and acute rejection of kidney graft.

Does the KIR2DS5 Gene Protect from Some Human Diseases?