Does the KIR2DS5 Gene Protect from Some Human Diseases?

Abstract

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 FindingsIn 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/SignificanceOur results suggest that KIR2DS5 may protect from endometriosis, ankylosing spondylitis, and acute rejection of kidney graft.

Lack of association between KIR genes and acute lymphoblastic leukemia in children

“…Given the consistently decreased frequencies of all KIR-S genes in the Almalte et al study, 1 it would be highly desirable to know inhibitory KIR gene frequencies in this cohort, which would help to understand how the distribution of KIR genotypes is affected. Unfortunately, PCR primers and amplification conditions used for KIR PCR-based KIR genotyping was performed as described by Vilches et al 3 As an additional quality control, 10% of samples were randomly selected and analysis repeated with an independent KIR typing protocol as described by Uhrberg et al 4 Similarly, all samples exhibiting rare KIR genotypes (frequency Ͻ 0.5%) were controlled in this way. 4 Samples with discordant typing results (n ϭ 9) were excluded from the analysis.…”

“…Unfortunately, PCR primers and amplification conditions used for KIR PCR-based KIR genotyping was performed as described by Vilches et al 3 As an additional quality control, 10% of samples were randomly selected and analysis repeated with an independent KIR typing protocol as described by Uhrberg et al 4 Similarly, all samples exhibiting rare KIR genotypes (frequency Ͻ 0.5%) were controlled in this way. 4 Samples with discordant typing results (n ϭ 9) were excluded from the analysis. (B) Distribution of group A and B KIR haplotypes according to previous definitions.…”

“…It is noteworthy that decreased frequencies of some activating KIR genes in ALL patients have been described. 3,4 The reasons for the discordant results in the 2 studies are not immediately apparent. However, we speculate that these differences may result from the use of different PCR primer sets.…”

Comparison of KIR gene content profiles revealed a difference between northern and southern Persians in the distribution of KIR2DS5 and its linked loci

“…KIR2DS5 is implicated in the outcome of bone marrow transplantation [37]. Moreover, studies suggest that the presence of KIR2DS5 is protective for psoriasis vulgaris, endometriosis, ankylosing spondylitis, and acute rejection of kidney graft [38,39]. Knowing the medical significance, it is an appealing hypothesis to determine whether KIR2DS5-enriched northern Persians are more resistant to developing these clinical conditions compared with those living in the southern part of the country.…”

Response: associations between activating KIR genes and childhood leukemia

“…It is noteworthy that decreased frequencies of some activating KIR genes in ALL patients have been described. 3,4 The reasons for the discordant results in the 2 studies are not immediately apparent. However, we speculate that these differences may result from the use of different PCR primer sets.…”