Characterization of Complement Receptor 1 haplotypes in individuals from Argentine

MUFARREGE N; MATTALONI S; COTORRUELO C; TRUCCO BOGGIONE C; LUJÁN BRAJOVICH M; BIONDI C; PRINCIPI C; GARCÍA BORRÁS S

Basilea

Congreso; 29th Regional Congress of the ISBT; 2019

International Society of Transfusion Medicine

Background: Complement Receptor 1 (CR1) is a membrane glycoprotein found at the surface of several human cells, especially erythrocytes and macrophages. Human CR1 expressed on erythrocytes plays a role in immune complex (IC) clearance. On the other hand, the expression of CR1 on macrophages, monocytes and neutrophil granulocytes mediates the uptake of complement-opsonized particles. Five distinct CR1 nucleotide substitutions have been described. One of them is located in intron 27 of CR1 gene and is associated to a HindIII restriction fragment-length polymorphism responsible for the H/L alleles. The other four SNPs are found in exon 29 and generate the Kna/Knb, McCa/McCb, Sl1/Sl2 y KCAM+/- Knops blood group antigens alleles. Genetic variations in CR1 may be involved in the recognition of opsonized microorganisms during an infectious disease. Aims: The aim of this work was to analyze CR1 haplotypes in samples from donors (D) and from tuberculosis (TB) and leprosy (L)patients. Methods: The five SNPs described (H/L; Kna/Knb; McCa/McCb; SL1/SL2; KCAM+/KCAM-) were genotyped in DNA samples from D (n=122) and TB (n=50) and L (n=43) patients using PCR-RFLP strategies. Haplotypic and allelic frequencies were obtained with the Arlequin® v3.5.2.2 software. Results: In the 122 D samples studied, the haplotypes H-Kna-McCa-Sl1-KCAM+(Freq: 0,760); L-Kna-McCa-Sl1-KCAM+(Freq: 0,189); H-Kna-McCa-Sl2-KCAM+(Freq: 0,016); L-Kna-McCa-Sl2-KCAM+(Freq: 0,008), H-Kna-McCb-Sl1-KCAM+(Freq: 0,004); and L-Kna-McCb-Sl2-KCAM+ (Freq: 0,004) were identified. However, in TB and L groups only two haplotypes were found: H-Kna-McCaSl1-KCAM+ (Freq: TB=0,740; L=0,744) y L-Kna-McCa-Sl1-KCAM+ (Freq: TB=0,260; L=0,256). The allelic frequencies obtained were: H(D=0,784; TB=0,740; L=0,744), L (D=0,202; TB=0,260; L=0,256), Kna (D=0,999; TB=0,999; L=0,999), McCa (D=0,992; TB=0,999; L=0,999), McCb (D=0,008; TB=0,001; L=0,001), Sl1 (D=0,971; TB=0,999; L=0,999), Sl2 (D=0,029; TB=0,001; L=0,001) and KCAM+ (D=0,999; TB=0,999; L=0,999). Even though no significant differences were found among the groups studied, 4 haplotypes containing the McCb and SL2polymorphisms were identified in D samples but were not found in TB and L groups. Summary / Conclusions: This preliminary data obtained suggests that CR1 polymorphisms and haplotypes, especially those containing McCb and Sl2 SNPs, could be involved in the disease pathogenesis of tuberculosis and leprosy. The entrance of mycobacteria into macrophages is mediated by complement receptors that facilitate their uptake by host cells so the combined haplotypes could be enhancing parasite phagocytosis and inflammation. Further studies are being carried out to establish whether CR1 polymorphisms are risk or protective factors and whether other genetic variations in this receptor are also involved.