MOLECULAR STUDY GENOTYPE MHC-C (LOW RESOLUTION), WHOLE BLOOD

Reference values and Delivery Time Modification

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Test New code: 9955

Effective update from 27/12/2023

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Results Format:       R1: See attached report	Result Format:       R1: KIR ligand genotype (HLA-C group)       R2: LOCUS C (Class I)       (a*) Interpretative text of the study

(a*) MOLECULAR STUDY HLA-C GENOTYPE (LOW RESOLUTION), WHOLE BLOOD

DETERMINATION

Molecular typing of human leukocyte antigen (HLA -C class I) alleles at the allele group level (low resolution).

TEST PRINCIPLE

The technique is based on the reverse hybridization principle. A P CR-SSO is carried out after DNA isolation.

At the PCR, amplification of exons 2 and 3 of the HLA-C locus occurs and PCR products are biotinylated. Then, amplification products are subsequently hybridized using a typing strip. This test is designed to give the best possible resolution at the allele group level (this means the first two digits after the asterisk in an allele name following standard HLA nomenclature, ex. Cw*07Cw*08), although resolution to the allelic level may be possible for the most allele combinations.

Interpretation of the results is based on the allele population frequency.

ALLELE GROUPS:

C1: C*01, C*03 (except C*03:07), C*07 (except C*07:07, C*07:09), C *08, C*12 (except C*12:04, C*12:05), C*14,C*15:07, C*16 (except C*16:02),C2: C*02, C*03:07, C*04, C*05, C*06, C*07:07, C*07:09, C*12:04, C *12:05, C*15 (except C*15:07), C*16:02, C*17, C*18

APPLICATION IN HUMAN REPRODUCTION

At a pregnancy, maternal uterine natural killer cells (UNKs) are the dominant immune cells in the uterine mucosa and there are multiple studies that support their important role in establishing normal early placentation (1, 2, 3, 4, 5, 6). There are also evidences of a dir ect ligand-receptor interaction between trophoblastic cells (which show HLA -C class I molecules) and UNKs KIR receptors. This interaction seems to

condition the process of placentation. HLA genotypes are organized into two groups (HLA -C1 and HLA-C2), and although both HLA-C1 and HLA-C2 bind to KIR receptors, the strength of the downstream UNKs response is str ongly influenced by C1 and C2 zygosity of

the new pregnancy. The extreme variability in both the maternal KI R and fetal HLA -C ligands means that each pregnancy will feature a range of different combinations. Therefor e, the balance of KIR genotypes in a given patient and the HLA-C exposure in a given pregnancy may influence the initiation of normal placentation (7).

 REFERENCES

(

1). Trundley A., Moffett A. Human Uterine Leukocytes and pregnancy. Tissue Antigens 2004; 63: 1-12.
(2). Caligiuri MA. Human natural killer cells. Blood 2008; 112: 461-9.
(3). Moffett A., Shreeve N. First do no harm: uterine natural kill er (NK) cells in assisted reproduction. Human
Reproduction 2015; 30: 1519-25.
(4). Pace D., Morrison L., Bulmer JN. Proliferative activity in en dometrial stromal granulocytes throughout
menstrual cycle and early pregnancy. J Clin Pathol 1989; 42: 35-9.
(5). Xiong S., Sharkey AM. Kennedy PR, Gardner L, Farrell LE, Cha zara O, et al. Maternal uterine NK cell -
activating receptor KIR2DS1 enhances placentation. J Clin Invest 2013; 123: 4264-72.
(6). Robson A. Harris LK, Innes BA, Lash GE, Aljunaidy MM, Aplin JD, et al. Uterine natural killer cells
initiate spiral artery remodeling in human pregnancy. FASEB J 2012; 26: 4876-85.
(7). Scott J. Morin, Nathan R. Treff, Xin Tao, et al. Combination of uterine natural killer cell immunoglobulin
receptor haplotype and trophoblastic HLA -C ligand influences the risk of pregnancy loss: a retrospective co hort
analysis of direct embryo genotyping data from euploid transfers.

 

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