KIR2DS5 in the presence of HLA-C C2 protects against endometriosis.
Endometriosis is defined as the presence of functional endometrial tissue outside the uterine cavity. Several hypotheses have attempted to explain the etiology and pathogenesis of endometriosis. Recently, it has been suggested that a defect of the natural killer (NK) activity in the recognition and lysis of endometrial cells is one of the crucial points in the development of this disease. Natural killer cells can express killer immunoglobulin-like receptors (KIR), which recognize class I human leukocyte antigens on target cells. We asked whether polymorphisms in KIR, HLA-C, and HLA-B genes are risk factors for endometriosis. We tested 153 women with endometriosis diagnosed on the basis of laparoscopic and histological examination, and 213 control healthy women, who gave birth to at least one child. The frequency of KIR genes in patients was similar to that in controls except for KIR2DS5, which exerted a protective effect only in HLA-C C2-positive individuals. Moreover, KIR2DS5-positive women with endometriosis had 13 times lower chance that the disease would occupy the peritoneum than KIR2DS5- and KIR2DS4del-negative ones (OR = 0.077, P = 0.0061). Similarly, KIR2DS4del-positive endometriotic persons had 11 times lower chance for peritoneal disease (OR = 0.094, P < 0.001). Negative linkage disequilibrium between KIR2DS5 and KIR2DS4del indicates that these genes are mutually exclusive. Our data suggest that KIR2DS5 may be associated with protection from endometriosis, whereas KIR2DS4del seems to be associated with higher disease stages, possibly by exclusion of protective KIR2DS5.
Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Rudolfa Weigla 12, 53-114, Wrocław, Poland, izan@iitd.pan.wroc.pl.
Izabela
I
Nowak
Rafał
R
Płoski
Ewa
E
Barcz
Piotr
P
Dziunycz
Paweł
P
Kamiński
Grażyna
G
Kostrzewa
Łukasz
Ł
Milewski
Piotr I
PI
Roszkowski
David
D
Senitzer
Jacek
J
Malejczyk
Piotr
P
Kuśnierczyk
D000328:Adult; D004715:Endometriosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D015810:Linkage Disequilibrium / Q000235:genetics; D008875:Middle Aged; D011044:Poland / Q000453:epidemiology; D054340:Receptors, KIR / Q000235:genetics*; D055815:Young Adult
D015236:HLA-C Antigens; C048767:HLA-C*02 antigen; C473953:KIR2DS4 protein, human; C531595:KIR2DS5 protein, human; D054340:Receptors, KIR