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ORIGINAL ARTICLE  
Year : 2013  |  Volume : 6  |  Issue : 2  |  Page : 183-187
Incidence of Kell blood group in Kashmiri population attending blood bank SKIMS as donors


Department of B.T and I.H, SKIMS, Soura, Srinagar, Jammu and Kashmir, India

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Date of Web Publication14-Aug-2013
 

   Abstract 

Purpose: To determine anti-Kell in Kashmiri population. Material and Methods: Prospective study of One Year. Result: Six patients were tested positive. Conclusion: The incidence of Kell is very low i.e., 0.03% and correlates to the incidence of Japanese.

Keywords: Blood bank, blood donors, incidence, Kell, Kashmir, pregnant ladies, SKIMS

How to cite this article:
Shah M, Shah FY, Shah FY. Incidence of Kell blood group in Kashmiri population attending blood bank SKIMS as donors. Ann Trop Med Public Health 2013;6:183-7

How to cite this URL:
Shah M, Shah FY, Shah FY. Incidence of Kell blood group in Kashmiri population attending blood bank SKIMS as donors. Ann Trop Med Public Health [serial online] 2013 [cited 2020 Feb 25];6:183-7. Available from: http://www.atmph.org/text.asp?2013/6/2/183/116508

   Introduction Top


In addition to the ABO blood group and Rhesus (Rh) antigens, there are over 400 other blood group antigens located on red cell surface. Transfusion recipients with negative antigens on their red cell surface, may develop antibodies against these antigens when transfused with such blood or components.

The first Kell system antibody was described in 1946, shortly after implementating the use of recently described rabbit anti-human globulin reagent. The importance of Kell system was obvious from the first case: an example of hemolytic disease of the new born. [1] A pregnant woman named Mrs. Kellacher was the first patient described with antibodies to K1. [2] Hence, the Kell group was named after her. Mrs. Cellano was likewise a pregnant woman with the first described antibodies to K2. The K0 phenotype was first described in 1957 and the McLeod phenotype was found in Hugh McLeod, a Harvard dental student, in 1961. [3],[4] Subsequent serological studies revealed the polymorphic complexity of the Kell blood group system. [5]

As with most systems, over the years, more antigens have been found that were proven by inheritance to be of the Kell blood group system. At present, it is a system comprised of 25 blood group antigens, several having been shown to be products of allelic genes. Some of the antigens have also shown a distinct racial prevalence (K antigen is more frequently found in Northern European, the Jsa antigen is most frequently found in those of African descent and the Kpc antigen has been found in Japanese).

All this was very suggestive of chromosome location that might have three or more regions with mutation points. [6]

The Kell system of blood groups may be looked upon as a pale shadow of the Rh system. Similarly determined by three closely linked loci, each of which can be occupied by one of the pair of allelic genes, K and K, Kpa and Kpb, and Jsa and Jsb. The K genes, like D in the Rh system, gives rise to an antigen to which mothers do not frequently become immunized, so that their infants suffer from haemolytic disease of the newborn. The K gene and its antigenic product are almost entirely confined to the white or Caucasian people, and Jsa to the Negroid or African ones. [7]

The Kell blood group system is an interesting mix of high-frequency and low-frequency antigens. It consists of 25 antigens, which include six pairs of triplets of antithetical antigens. All of these polymorphisms represent Single Nucleotide Polymorphisms SNP's encoding amino acid substitutions on the Kell glycoprotein. The two antithetical antigens (K and k) remain the most common of the system. K has a frequency of about 9% in a Caucasian population, and about 3.6% in blacks. Despite the low quantity of K antigens on the Red Blood Cells (RBC) surface (3,500-6,000 K copies/cell), it is very much immunogenic. It can be detected on fetal RBC's as early as 10 weeks of gestation. Outside the ABO and Rh antibodies, anti-K is the most common antibody seen in the blood bank. It is usually made in response to antigen exposure through pregnancy or previous transfusion and can persist for many years. The antibody is therefore important in transfusion medicine, autoimmune hemolytic anemia (AIHA), and hemolytic disease of the newborn (HDN). People without Kell antigens (K0) must be transfused with blood donors who are also K0 to prevent hemolysis. [7],[8],[9],[10]

The importance of the association of Kell and XK was deduced from studies on the K0-null, McLeod phenotypes and recognition of the clinical symptoms that accompany the McLeod phenotype. Isolation of Kell and XK proteins from red blood cells, with specific allo-immune antibodies, demonstrated that Kell antigens are carried on a 93 kDa protein and KX on a protein that migrates on SDS-PAGE as a 37 kDa polypeptide. Molecular cloning followed, establishing Kell as a type II glycoprotein homologous with zinc endopeptidases and XK as a unique protein that spans the membrane ten times. The many polymorphic forms of Kell, which express different antigens, were shown to be due to single base changes that encode different amino acids. The disulfide linkage of Kell and XK was demonstrated as occurring between kell Cys 72 and XK Cys 347. The Kell component of Kell/XK complex was shown to be an enzyme that preferentially cleaves big endothelin-3, an inactive intermediate precursor, at Trp 22-I1 e22, producing endothelin-3, and a potent 21 amino acid peptide. The endothelins are potent vasoconstrictors that also act as mitogens and are involved in developmental processes by affecting migration of neural crest derived cells. [11]

Although HDN is most common in Rh alloimmunization, about 0.1% of all obstetric patients have maternal antibodies to K antigen. Maternal antibodies are usually due to transfusions of mismatched blood, although immunizations from previous pregnancies can occur. In contrast to HDN caused by antibodies to Rhesus D antigen, there is a poor correlation between maternal anti-K and the severity of the disease. It has been suggested that fetal anemia, due to Kell antibodies is due mostly to suppression of erythropoiesis rather than to hemolysis. in vitro studies have demonstrated that the anti-K inhibits the growth of K + progenitor cells. [12]

K0 gene is a silent allele. The inheritance of two K0 genes results in the recessive null phenotype. K0 RBCs lack expression of all Kell antigens. These individuals typically make anti-Ku that recognizes the "universal" Kell antigen present on all cells except K0. Anti-Ku has caused both HDN and Hemolytic Transfusion Reaction (HTR). Such individuals should only receive K0 blood. [13]

Although the frequency of anti K is very less in blacks, we tried to estimate the prevalence of Kell antigen in our population and record incidence of Kell blood group in Kashmiri population which could be used to predict which females are prone to develop HDN and to prevent AIHA and transfusion reactions. This study is first of its kind in Kashmiri population. Hence, we conducted a prospective study for a period of one year.

Aims of the study

To study the incidence of Kell blood groups in Kashmiri population, thereby:

  1. To know the prevalence of Kell in Kashmiri population.
  2. To reduce the chances of Kell related transfusion reactions in patients.
  3. To prevent occurrence of HDN

   Material and Methods Top


This study was conducted upon blood donors attending Blood Bank of Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Kashmir (India). 2,000 subjects were included in the study over a period of 1 year from July 2010 to June 2011. 200 donors from each district of the valley were randomly selected and a total of ten districts were included in the study.

Since the number of female donors was less than 7%, other pregnant females who were referred from Gynecology department of SKIMS for testing unexpected antibodies were also included. In this study, their blood samples were collected in EDTA vials. All donors were examined and were declared fit for donation as per guidelines of AABB.

From those 2000 donations, there were 1704 males and 296 females who were tested for Kell antigen.

The human monoclonal anti-K sera and positive (KK and negative KK) controls were obtained from Immucor Gamma 3130, Gateway Driver, NORCRSS, GA30071 & USA.

Specimen collection and preparation

Samples were drawn from blood collection bags which contained anticoagulants. Tests on blood samples were transformed and results were confirmed within a period of two days of donation or collection, thereby reducing the chances of any error due to contamination/improper storage.

Procedure

Three methods are available for detecting Kell antigen, e.g. slide method, tube method and micro-plate or micro-well method. We selected tube method for our study, as it is a simple, reliable and cost effective method. It allows for long incubation without any drying (unlike slide method which causes drying of blood giving false impression of agglutination). The tubes can be centrifuged to enhance Ag, Ab reaction.

Requirement

  • 10×75 mm test tubes
  • Test tube rack
  • Anti-K series 2(human Monoclonal)
  • Serological centrifuge.
Method

One drop of 3% - 5% RBC suspension-sample collected from blood donation bags and in case of females who were required to be tested for unexpected antibodies, their samples were taken as 1 drop of blood from EDTA vial. (1 drop of EDTA blood mixed with 1 ml 0.9% physiological saline) was mixed with one drop of monoclonal anti-K in 12× 75 mm test tubes. The tubes were then centrifuged for 1 minute at 2000 rpm. After re-suspension by agitation, the tubes were examined for agglutination. All negative tubes were incubated at room temperature for 15 minutes, centrifuged and looked for agglutination. The same procedure was applied on the positive and negative controls.


   Results Top


Kashmir Province (India) is composed of 10 districts i.e. Srinagar, Pulwama, Budgam, Ganderbal, Kulgam, Shopian, Anantnag, Baramulla, Kupwara and Bandipore. The population in these districts ranges from medium to very high with an average of 200 per sq.km.

The area of Kashmir Province is 15668 Sq.km with a population of 70.47 lac (Census 2010). There are many communities in Kashmir i.e. Muslims, Pandits, Sikhs and Christians. Muslims are in majority.

Samples were tested in both males and females. Donor samples of females were less than 15% (including those who were pregnant and attended Blood Bank for determination of unexpected antibodies were also included in the study and tested for Kell antibodies [Table 1], [Figure 1].
Figure 1: Showing gender of the studies subjects

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Table 1: Kell analysis with respect to gender of the studied subjects

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All the subjects were fit and healthy and in the age group of 18 to 60 years, having Hb value between 12.5 g/dl to 16.8 g/dl. Their weight ranged from 55Kg to 88Kg. The study was carried over a period of one year. The total number of donors screened for anti-Kell was 2000. The major ABO blood group in the donors tested for Kell group was as follows and is depicted in [Table 2] and [Table 3] and [Figure 2].
Figure 2: Showing blood group of the studied subjects

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Table 2: Blood group in the studied subjects

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Table 3: Blood group in the studied subjects

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In our study, the number of O group donors was 711(35.50%), B group 641 (32.05%), A group 482(24.1%), AB group 166(8.3%) [Table 4]. This corresponds to the general trend of blood groups in other population studies. But Rh negative blood was seen only in 8% of donors studied against world literature of 15% Rh negative bood in other populations.
Table 4: No. of donors with different blood groups

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Only 6 out of 2000 donors were tested positive for anti-Kell. The result of the study is shown in [Table 5].
Table 5: Frequency of Kell Blood group in Kashmiri population

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A total of 2000 blood samples were phenotyped for K-antigen [Table 4].

It is interesting to note that out of 6 positive Kell donors, 4 were among O+ve group and 2 from blood group B+ve. None was positive from other groups. Why only O+ve and B+ve donors tested positive is not clear and no literature supports the incidence of Kell positive antibodies in any particular group.


   Discussion Top


The expression of Kell antigen is different in different populations all over the world. There is racial and ethnic difference in expressing Kell antigen. The maximum expression of Kell antigen on red cell surface is seen in Caucasians with no antigen on RBC sample of Kwalos population.

Anti-Kell is third most potent immogenic antibody (IGg1) after ABO and Rh which causes transfusion reactions and is a cause of hemolytic disease of newborn (HDN). [8],[9],[10]

Although most examples of anti-kell are stimulated either by pregnancy or transfusion, a new case of apparently non-red cell immune anti-Kell have been described. In some cases, the antibodies are found in untransfused, healthy, male blood donors, in other microbial infections were implicated as an immunizing agent. Since, the frequency of the anti-Kell is very low and non-red cell immune anti-Kell may be present in the serum of donor population. The routine screening of blood donors is not recommended and is not being done in most of blood banks of the developing countries. Whenever any transfusion reaction, AIHA and pregnant women wherein chances of HDN are expected, the anti-Kell antigen screening is recommended. The third most immunogenic antibody is that of Kell. It is also advisable to test for anti-Kell in persons who are positive for unexpected antibodies. The persons who have received multiple transfusion/multi-parity, also need to be tested for anti-Kell antibodies.

In our study, 6 out of 2000 subjects screened for anti-Kell were positive. This is a very low frequency of anti-Kell in Kashmiri population (0.03%). The same frequency has been seen in Japanese (0.02%).


   Conclusion Top


Kell antigen testing was carried in random population of 10 districts of Kashmir province from all rural and urban areas which encompassed a total of 2000 subjects comprising of 1704 males and 296 females.

Six donors were tested positive who were all males and had no previous history of transfusion.

It has been reported that in the population of different ethnic and racial, the incidence of Kell antigen is reported to be rare to a maximum of 9% in Caucasians.

The genetic and environmental factor, previous transfusion, pregnancy and factors responsible for varying frequency needs to be probed further.

The present study has shown the incidence of Kell is very low i.e. 0.03% and correlates to the incidence with Japanese.

Further studies need to be carried out a large sample size and in other Provinces of the State.

 
   References Top

1.Daniels G. The molecular genetics of blood group polymorphism. Transpl Immunol 2005;14:143-53.  Back to cited text no. 1
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2.Mourant AE. Blood Relations, Blood Groups and Anthropology. Oxford, UK: Oxford University press; 1983.  Back to cited text no. 2
    
3.SCARF Exchange. Available from: http://scarfex.jove.prohosting.com/. [Last accessed]  Back to cited text no. 3
    
4.Weiner CP, Widness JA. Decreased fetal erythropoiesis and hemolysis in Kell hemolytic anemia. Am J Obstet Gynecol 1996;174:547-51.  Back to cited text no. 4
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5.Danek A, Rubio JP, Rampoldi L, Ho M, Dobson-Stone C, Tison F, et al. McLeod neuroacanthocytosis: Genotype and phenotype. Ann Neurol 2001;50:755-64.  Back to cited text no. 5
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6.Conneally PM, Dumont-Driscoll M, Huntzinger RS, Nance WE, Jackson CE. Linkage relations of the loci for Kell and phenylthiocarbamide taste sensitivity. Hum Hered 1976;26:267-71.  Back to cited text no. 6
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7.Coombs RR, Mourant AE, Race RR. A new test for the detection of weak and incomplete Rh agglutinins. Br J Exp Pathol 1945;26:255-66.  Back to cited text no. 7
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8.Lee S, Wu X, Reid M, Zelinski T, Redman C. Molecular basis of the Kell (K1) phenotype. Blood 1995;85:912-6.  Back to cited text no. 8
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9.Lee S, Lin M, Mele A, Cao Y, Farmar J, Russo D, et al. Proteolytic processing of big endothelin-3 by the kell blood group protein. Blood 1999;94:1440-50.  Back to cited text no. 9
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10.Yu LC, Twu YC, Chang CY, Lin M. Molecular basis of the Kell-null phenotype: A mutation at the splice site of human KEL gene abolishes the expression of Kell blood group antigens. J Biol Chem 2001;276:10247-52.  Back to cited text no. 10
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11.Denise M Hamening. Modern Blood banking and Transfusion Practices. 5 th ed. Baltimore, Maryland: University of Maryland School of Medicine; 2005. p. 175-80.  Back to cited text no. 11
    
12.Russo D, Wu X, Redman CM, Lee S. Expression of Kell blood group protein in nonerythroid tissues. Blood 2000;96:340-6.  Back to cited text no. 12
[PUBMED]    
13.Lee S, Russo DC, Reiner AP, Lee JH, Sy MY, Telen MJ, et al. Molecular defects underlying the Kell null phenotype. J Biol Chem 2001;276:27281-9.  Back to cited text no. 13
[PUBMED]    

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Correspondence Address:
Faisal Younis Shah
318, Mustafabad, Gousia Colony, Bemina, Srinagar
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1755-6783.116508

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