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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 6  |  Issue : 1  |  Page : 81-85

RH phenotype, ABO and kell antigens, alleles and haplotypes frequencies in North Indian blood donor population


Department of Transfusion Medicine and immunohematology, Sri Balaji Action Medical Institute, New Delhi, India

Date of Submission17-Mar-2021
Date of Decision17-Mar-2021
Date of Acceptance25-Mar-2021
Date of Web Publication29-May-2021

Correspondence Address:
Dr. Sadhana Mangwana
Department of Transfusion Medicine and immunohematology, Sri Balaji Action Medical Institute, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/gjtm.gjtm_23_21

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  Abstract 


Background and Objectives: ABO, RH and Kell blood group systems are clinically significant blood group systems among 36 blood group systems having total of 360 blood group antigens which cause most cases of alloimmunization following blood transfusions or pregnancy. India has regionally and ethnically very diverse population in different demographic areas. Due to different antigenic expression in different population, knowledge of antigen frequencies among their local and regional donor population is important to assess the risk of antibody formation, probability of antigen negative blood for patients having alloantibodies, inventory management and database for rare antigens thus enhancing patient safety. Aim: To know and compare phenotype prevalence, frequency distribution of ABO, RH and Kell antigens and Alleles in blood donors. Methods: A prospective study was conducted in a tertiary care hospital in North India over three years period. ABO, RH D grouping, RH and Kell phenotypes were performed on blood donors. Hardy Weinberg's equations were used to calculate ABO, RH and Kell allele frequencies and were analyzed. Results: During the study period, 24745 healthy individuals donated blood at Tertiary Care hospital; with 97.26% male and 2.74% female population. Prevalence of ABO antigens were B =37.74%, O = 31.38%, A = 21.77% and AB = 9.09% with allele frequency for O = 0.560, B = 0.266, A = 0.169 and AB = 0.091. The commonest RH phenotype observed was DCCee followed by DCcee, DCcEe, DccEe while commonest RH negative phenotype were ccee and Ccee. Homozygous phenotypes were absent in our population. Amongst five RH antigens phenotyped serologically, highest prevalence was of e antigen followed by D, C, c and E being the lowest. Prevalence of Kell phenotype was 2.57% (K) while that of k as 97.43% with allele frequencies of K and k as 0.0252 and 0.986 respectively. Discussion: Genetic variability in different population result in varied expression of red cell antigens in different races. Knowledge of varied frequency and phenotypic expression of major clinically relevant antigens and RH haplotypes in these blood groups systems would help in more rational approach for blood transfusion, decreasing alloimmunization thus enhancing blood safety.

Keywords: ABO, alleles and haplotypes, kell antigens, RH phenotype


How to cite this article:
Mangwana S, Simon N, Sangwan L. RH phenotype, ABO and kell antigens, alleles and haplotypes frequencies in North Indian blood donor population. Glob J Transfus Med 2021;6:81-5

How to cite this URL:
Mangwana S, Simon N, Sangwan L. RH phenotype, ABO and kell antigens, alleles and haplotypes frequencies in North Indian blood donor population. Glob J Transfus Med [serial online] 2021 [cited 2021 Dec 7];6:81-5. Available from: https://www.gjtmonline.com/text.asp?2021/6/1/81/317127




  Introduction Top


ABO, RH and Kell blood group systems are most important clinically significant blood group systems. International Society of Blood Transfusion recognizes currently among 36 blood group systems having total of 360 blood groups. RH blood group is one of the most complex and second most important blood group systems after ABO, having 62 antigens; the latest denoted as 62, a high prevalence antigen.[1] Frequency of D phenotype is more than 99.5% in East Asia and 85% in Caucasians.[2] Since the antibodies against high frequency antigens are relatively infrequent and antibodies against low or medium frequency with high antigenicity are more frequent; knowledge of antigens, their frequency and prevalence distribution, patterns of inheritance among different populations have been studied extensively in Western literature with few studies from India.[3],[4],[5],[6],[7],[8],[9] India has a very diverse population in different demographic areas, knowledge of antigen frequencies is important for patient and donor population to assess the risk of antibody formation, probability of antigen-negative blood for patients with red cell alloimmunization, inventory management and database for rare antigens.

Aim

The study was aimed to know the RH phenotype prevalence, frequency distribution of ABO, RH and Kell antigens and Alleles in Indian blood donors in this part of country and to compare with other ethnic groups and population, to reduce alloimmunization and to provide transfusion support to multitransfused patients with alloantibodies thus enhancing blood safety and generating database of donors with rare antigens.


  Methods Top


This prospective study was done in a Tertiary care hospital in Northern India over 3 year's duration, from May 2016 to May 2019. 2 ml EDTA samples were taken from 24745 blood donors and ABO, RH D grouping, RH and Kell phenotypes were performed by monoclonal antisera Anti A, Anti B, Anti AB (Immucor US) for cell grouping, Anti D Series5, Anti D Novaclone (Immucor, US) for RH Typing, and monoclonal Anti C, Anti c, Anti E, Anti e and Anti K, on a fully automated Immunohematology analyser using hemagglutination principal (Neo, USA). Statistics and data compilation and prevalence of antigens is calculated using excel tool. Hardy Weinberg's equation was used to calculate ABO and Kell allele frequencies. Observed and predicted allele frequencies and various ABO, RH and Kell antigens were analyzed and compared.


  Results Top


During the study period, 24745 healthy individuals donated blood at Tertiary Care hospital in capital city with age ranged from 18 to 65 years. There were 97.26% (24,067) males and 2.74% (678) females. Prevalence of ABO antigens were B = 37.74%, O = 31.38%, A = 21.77% and AB = 9.09% with allele frequency for O = 0.560, B = 0.266, A = 0.169 and AB = 0.091 [Figure 1]. Prevalence of Kell phenotype was 2.57% (K) while that of Celino (k) as 97.43% with allele frequencies of K and k as 0.0252 and 0.986 respectively [Figure 2].
Figure 1: ABO antigen and allele frequency

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Figure 2: Kell antigen and allele frequency

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The D antigen (RH 1) was observed in 94.53% (n = 23392) with 5.47% (n = 1353) of blood donors showed D negative antigen.

The most common RH phenotype in D positive donors was observed CCDee (R1R1; 42.54%) followed by DCcee (R1r; 31.31%), DCcEe (R1R2; 13.07%), DccEe (R2r; 3.9%) [[Table 1]; Highlighted pink] while the most common RH negative phenotype was ccee (rr; 4.88%) and Ccee (0.43%) (Highlighted Green). Homozygous phenotypes (DCCEE and ccEE in RH negative) were absent in our population (Highlighted Yellow) [Table 1]. Of the 5 RH antigens phenotyped serologically, highest prevalence was of e antigen (98.79%) followed by D, C, c, (94.53%, 86.28%, 58.57% respectively) and E being the lowest (19.66%) [Figure 3].
Table 1: Antigen frequencies

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Figure 3: RH antigen frequencies

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Principal RH haplotypes prevalence for positive donors in this study was R1 (DCe) as 66.7% followed by R2 (DcE), R0 (Dce) and Rz as 7.7, 1.2 and 0.1% respectively while principal RH haplotypes prevalence for negative donors was r (ce) as 24.15% followed by r'(Ce), r''(cE) and ry (CE) as 0.2,0.05 and zero % respectively [Table 2].
Table 2: Prevalence of principal RH haplotypes

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  Discussion Top


Genetic variability in different population result in varied expression of red cell antigens in different races. Our result of B antigen prevalence in ABO system was similar to other reports in northern and eastern India,[9],[11] with O showing highest allele frequency (0.560); similar to observation by Basu et al. from eastern India.[11]

Prevalence of RH (D) antigen (94.53%) was similar to previous reports from India [Table 2],[5],[6],[7],[8],[9] but there are tremendous variations in prevalence of RH (D) antigen in blood donors worldwide, varying from 83% to 85% in European and American populations while 99%–100% in Japanese, Chinese population.[12] This major difference in the distribution of RH (D) antigen in the different population groups has a clinical significance as D is the most important red cell antigen after A and B, and antibodies are considered potential agents of hemolytic disease of newborn and of hemolytic transfusion reaction and causing alloimmunization of multitransfused patients.[7],[13]

Knowledge of the distribution of RH (D) antigen in blood donor population also helps in formulating policies regarding pre transfusion testing. For instance, the frequency of RH (D) negative person among the Taiwanese population is 0.3%; hence, the incidence of anti-D in Taiwanese population is very uncommon i.e., 1 in 295,000 blood donors. As a result of these findings, routine RH (D) typing in Taiwanese hospital patients requiring blood transfusion has been discontinued.[14]

Prevalence of Kell antigen varied markedly amongst Indian population. Our observation of Kell (K) antigen prevalence of 2.57% was similar to other northern Indian and European population (7.82%–Germany) while eastern Indian population had very low Kell antigen prevalence of 0.79%. [6, 9, 11, 15]

The commonest RH phenotype observed in this study in D positive donors was CCDee (R1R1) followed by CcDee (R1r), CcDEe (R1R2), ccDEe (R2r); similar findings observed in various Indian studies. [6, 7, 9, 16] However, similar results are observed in only 17.6% of white and 2.9% of black population.[2],[10],[17] The ccDee (R0r) phenotype frequency in our population is only 2.4% ; comparable with other Indian data (Sarkar et al. [2.2%] and Makroo et al. (1.15%), Basu et al.[0.98%]) in contrast to 22.9% prevalence in African blocks.[4],[6],[11] The commonest RH negative phenotypes in this study were ccddee (rr) and Ccddee (r'r) as 4.87 and 0.42%; similar to findings by Sarkar, Makroo et al. and Basu et al. who observed rr prevalence as 0.3, 4.76 and 2.75% respectively and r'r prevalence as 2.5, 2.37 and 0.52% respectively.[4],[6],[11]

Homozygous phenotypes (CCDEE, RzRz and ccddEE, r”r” in RH negative) were absent in our population. Rare blood group is the one that, on the basis of the blood group characteristics are considered having frequency of ≤1:1000 random samples in a given population or red cells lacking a high-frequency blood group antigen or blood that lacks multiple common antigens.[18] Rare nature of a blood type may vary from one country to another and therefore a blood type rare in one country may not be considered rare in another. Rare blood groups in our population were of phenotypes as CCDEE, (RzRz) CCddee (r'r'), CcDEe (R1Rz), CcDEE (R2Rz), ccddEe (r”r), CcddEe (r'r”) and ccddEE (r”r”) (frequencies as zero, zero, 0.01, zero, 0.01, zero and zero respectively); similar to other findings from Indian subcontinent as observed by Makroo et al.[6] Prevalence of these rare phenotypes is lower in our population than among Caucasians.[19],[20]

Of the five in RH negative antigens phenotyped serologically, highest prevalence was of e antigen (98.79%) followed by D, C, c, (94.53%, 86.28%, 58.57% respectively) and E being the lowest (19.66%); findings similar to other studies in North and western India population, [Table 3][5],[6],[7],[8],[9],[11] but different when compared to different ethnic groups around the world.[3],[4]
Table 3: Comparison of RH antigens in various Indian studies

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The most common RH haplotypes in our population was DCe (R1; 0.667), followed by dce (r; 0.2415); similar to north and eastern Indian population,[6],[10] endorsing the earlier observation by Makroo et al. that CCDee (R1R1) is the most common phenotype in Indian population but different when compared with different ethnic groups [Table 2].[4],[6],[10]

Present study supports the view that ethnic and regional differences do exist in distribution and prevalence of RH antigens and phenotypes. Antibodies against RH antigens are the most common cause of alloimmunization especially in multitransfused patients as observed in our previous study that 68% alloantibodies in oncology patient were observed from RH blood group system.[13]

To conclude, Knowledge of antigen frequency of RH antigens would be helpful in serological investigations and transfusion support to multitransfused patients with presence of alloantibodies. Prevalence of RH negative donors is sufficiently high to maintain required inventory of RH negative units to support RH negative patients. With around 8000 annual blood donations at our centre with 5.47% of RH negative donations imply that more than 400 RH negative blood units are donated per year. This data will help the department in maintaining adequate stock of RH negative donors. Knowledge of varied frequency and phenotypic expression of major clinically relevant antigens and deriving estimates for underlying ABO and KEL alleles and RH haplotypes in these blood groups systems would help in more rational approach for blood transfusion with appropriate antigen matched blood decreasing alloimmunization and enhancing blood safety. Outcome of such studies can be used to formulate a rare blood group registry at regional and National level and directing patients with antibodies against high frequency antigens, requiring multiple transfusions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Sarkar RS, Philip J, Mallhi RS, Yadav P. Proportion of Rh phenotypes in voluntary blood donors. Med J Armed Forces India 2013;69:330-4.  Back to cited text no. 7
    
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Kahar MA, Patel RD. Phenotype frequencies of blood group systems (Rh, Kell, Kidd, Duffy, MNS, P, Lewis, and Lutheran) in blood donors of south Gujarat, India. Asian J Transfus Sci 2014;8:51-5.  Back to cited text no. 8
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Mangwana S, Kacker A, Simon N. Red cell alloimmunization in multi-transfused, oncology patients: risks and management. Global J Transfus Med 2019;4:74-8.  Back to cited text no. 13
    
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Datta SS, Reddy M, Basu S. Warm autoimmune hemolytic anemia with mimicking anti-e specificity causing intravascular hemolysis in a chronic ITP patient. Transfus Apher Sci 2015;53:205-7.  Back to cited text no. 15
    
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Reesink HW, Engelfriet CP, Schennach H, Gassner C, Wendel S, Fontão-Wendel R, et al. Donors with a rare pheno [geno] type. Vox Sang. 2008;95:236-53. [doi: 10.1111/j. 1423-0410.2008.01084.x].  Back to cited text no. 18
    
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Peyrard T, Pham BN, Elghouzzi MH, Martin A, Boutou P, Beolet MT, et al. A large scale epidemiological study reveals that the rare: -1,2,-3,- 4,5, :--1,-2,3,4,-5,: 1,2,3,-4,-5 blood groups appear less prevalent than expected in the French population. Vox Sang 2010;99 Suppl 1:361.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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