Association of Polymorphisms in the HLA-C Locus with Disease Risk for Developing Acute Graft Vs. Host in Pediatric Patients with Allogeneic Hematopoietic Stem Cell

The acute graft versus host disease (aGVHD) is the most common complication subsequent to allogeneic hematopoietic progenitor cell donor match HLA  ( Human Leukocyte Antigen) , occurring in 30-50%. In hematopoietic progenitor transplantation (HSCT) there are  other genetic factors such as minor histocompatibility antigens and citokines . The HLA-C locus has been divided into two groups according to the amino acid at position 80, this variation is important for the type of KIR   (, killer cell Ig-like receptor). The C1 group contains a lysine at position 80 and includes Cw2, -4 alleles -, - 5, -6, -15; The group includes C2 Cw1, -3, -7, -8 alleles contains an asparagine at position 80 alleles of the C1 group for KIR2DL1 and KIR2DS1 receptor and group C2 alleles bind to KIR2DL2 receptors bind and KIR2DL3. The interaction of the different alleles of HLA-C locus with KIR receptors expressed on NK cells cytotoxic activity changes which influence the risk for development of aGVHD.

Our objective was to determine the association of polymorphisms of HLA-C locus with the risk of developing aGVHD in pediatric HSCT patients.

All patients who underwent HSCT from an HLA identical related donor in the period between January 2008 and September 2013.  . HLA results that were taken as part of the protocol for HSCT were analyzed. Descriptive statistics and the difference between the groups that developed aGVHD was performed with chi2, and the odds ratio (OR) was calculated as a measure of association, is also the 95% calculation.

 Nine patients (28.12%) developed aGVHD and  8/9 patients (88.9%) were carriers of an allele group HLA-C C1 OR 38;  95% CI  3.7 - 395; p = 0.0002. Of the 23 patients who did not develop aGVHD, 19 (82.6%) were carriers of at least one allele of the group C2, RM 0.0263; 95% CI 0.0025 to 0.2735; p = 0.0002 (TABLE 1)

 

Patients with aGVH	Patients without Agvh
Group C1 Cw2,-4,-5,-6,-15  (n9)	Grupo C2 Cw1,-3-7-8  (n23)
Cw4-Cw4	Cw3-Cw6
Cw4-Cw7	Cw3-Cw12
Cw3-Cw4	Cw3-Cw8
Cw4-Cw7	Cw3-Cw1
Cw4-Cw12	Cw3-Cw7
Cw6-Cw7	Cw3-Cw7
Cw1-Cw6	Cw3-Cw4
Cw2-Cw7	Cw7-Cw4
Cw7-Cw7	Cw4-Cw15
	Cw7-Cw8
	Cw3-Cw8
	Cw3-Cw4
	Cw6-Cw7
	Cw3-Cw7
	Cw6-Cw7
	Cw1-Cw7
	Cw7-Cw8
	Cw3-Cw7
	Cw4-Cw6
	Cw6-Cw12
	Cw3-Cw16
	Cw4-Cw12
	Cw1-Cw4