|Year : 2021 | Volume
| Issue : 3 | Page : 2-4
|Oration - Dr Sanmukh Joshi
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|Date of Web Publication||29-Apr-2021|
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. Oration - Dr Sanmukh Joshi. Asian J Transfus Sci 2021;15, Suppl S1:2-4
Title : Discovery of blood groups in India –an update
Author : Sanmukh R. Joshi
Institute : Lok Samarpan Regional Blood Bank and Research Centre, Surat
Correspondence : Dr. Sanmukh R. Joshi, Lok Samarpan Blood Bank and Research Centre, Minibazar, Varachha Road, Surat-395006, Gujarat State, India. Phone (Cell): +91 7715915574. E-mail: [email protected]
Running title : Discovery of blood groups
Keywords : Discovery, blood groups, India
Human blood groups comprise over 375 antigens that are classified into 43 blood group systems. These blood groups were discovered over a period of past 120 years. Discovery of different antigens were made in different parts of the World, mainly from the Western countries. India has also contributed its share through original findings as outlined in this article.
Human blood groups comprise over more than 375 antigens, as of 9th December 2020, which are classified into 43 blood group systems as per genetic association. These were discovered in a span of 120 years, mainly by scientists from the Western World. India has also made respectable contributions with a few original discoveries. Steve Pierce and Marion Reid from the USA have recently compiled data in a form of a book entitled “Bloody Brilliant! A history of Blood groups and Blood groupers”, AABB Press (2016). The blood groups discovered in India are outlined below:
It was discovered in the year 1951 by H.M. Bhatia at the KEM Hospital, Bombay while the search for a compatible blood unit for a patient met with a railway accident. While the patient was grouped as O, none of the 115 units were found to be compatible due to a presence of an antibody to the high-frequency antigen (HFA) in his serum. In a span of one month, he got another patient with similar features and was compatible with the first case. A deliberate search among the donors yielded one more case with identical character. The blood specimen from these three individuals were referred to the Blood Group Reference Unit in the UK where it was defined as a “new” blood group that was named later as “Bombay group” or Oh phenotype denoting an absence of HFA antigen H on RBCs with naturally occurring regular alloanti-H in plasma. Discovery was instrumental in understanding the Biosynthetic pathway of the ABH antigens. Later, a systematic survey among the 42,297 persons in Bombay, now known as Mumbai, got 3 individuals with this phenotype showing its incidence as 1:13000 in the city. Further screening on a larger sample size of 1,67,404, the incidence was worked out to be 1:7,600, half of which came from the South-West Maharashtra and Goa. A systematic survey was carried out among 400 villages in these regions with further improved its occurrence as 1:4000. Meanwhile, 179 cases were referred from different parts of India, mainly from the Western & Southern regions and 179 of those were identified as the Oh phenotype. The State-wise distribution showed 122 cases from Maharashtra, 15 cases from Karnataka, 8 cases from Andhra Pradesh (integrated with the present-day Telangana), 6 cases from Goa and 5 from Gujarat. Sporadic cases were also found among the other Indian states as well.,,.
The Ii blood group, developmental antigen system, i.e., I antigen, weakly expressed on the RBCs at birth, gradually turns stronger in the first 18 months of life and remains stable through the rest of the life. Conversely, i antigen is strongly expressed at birth and gradually weakens through the period. As such, most adults are typed as I+i- while the Infants are typed as I-i+. The rare adults with I-i+ phenotype, similar to newborns, are under the genetic influence and the heterozygous display an intermediate pattern referred to as I-int. The adults with I-i- phenotype, with suppression of I akin to the newborn, with no compensatory rise of i, as is found in adult-I phenotype, were found among the healthy blood donors with a frequency of 1:900. The trait was found to be familial in nature, though it does not follow Mendelian inheritance, presumably due to complexity in interaction at the bio-synthetic level with ABH antigens. One large-kindred family of 95 members distributed in 4 generations, there were 15 subjects were I-i- and 6 others were with partial I expression. The phenotype in this family and 4 other families have carried A1 or A1B blood groups and the strength of A1 antigen was expressed higher than the control groups with the normal complement of the i antigen on their RBCs.
Indian Blood groups
Ina antigen was detected by a contaminant antibody present in the immune anti-D serum referred by a diagnostic firm in Surat. The additional antibody was isolated by differential absorption-elution experiments using a panel of red cells. It agglutinated by saline tube method but better reactivity was observed by indirect antiglobulin test (IAT). The antibody did not react with RBCs pretreated by papain enzyme. It reacted with RBCs of about 2-3% of the random donors in Mumbai. The isolated antibody from the original serum was sent to the Blood Group Reference Laboratory (BGRL), London where it was confirmed to be directed to a “new” antigen; we named it Ina. The significance of this discovery was appreciated as 30 different anti-D sera produced for reagent preparation were found to have anti-Ina as contaminant antibody with the implication that, some 2-3% D-negative individuals might have erroneously typed and received the D-positive blood transfusion! The reason for the stimulation of anti-Ina in these anti-D sera was that several Rh.D neg (subtype dce/dce) donors were immunized using RBCs of one person (subtype Dce) who incidentally possessed Ina antigen on his RBCs. The discovery paved the way to identify its antithetical antibody, name Salis, to an HFA detected some 6 years earlier. The Salis was renamed as anti-Inb. With this, a new blood group system was born, named INDIAN, and later on assigned the alpha-numeric symbol IN 023 by the International Society of Blood Transfusion. The system was further expanded when other HFAs, INFI (In3) and INJA (In4), INRA (In5), INSL (IN6) were found in people of Moroccan, Pakistani, Indian and Sri Lankan origin respectively.,,
INRA (In5), another HFA, the antibody to which was found in a course of compatibility tests for a female who was posted for surgical treatment. The antigen, sensitive to enzyme papain and chemical AET, was suspected for its specificity within the Indian system. The Inb, an HFA of the INDIAN blood group system was ruled out, as her RBCs were agglutinated by 2 examples of anti-Inb sera. The other HFAs of the system, viz. In3 and In4 were ruled out as our patient's RBCs were typed positive for both these antigens. Her RBCs were also typed positive for other known HFAs outside of the INDIAN blood group system like Kna, McCa, Yta, U, Vel, Ena, Kpb, Jsb, Wrb, Ge, CD99 excluding these specificities. Besides, the possibility of our patient to be with other rare phenotypes like Gerbichnull, Rhnull, D- -, MkMk, Fy(a-b-), Gy(a-), and Ko, was also ruled out. It was then established that the specificity of antibody in our case was directed to a hitherto unknown antigen. A striking observation on the antibody showing significant weak reactivity with RBCs from Lu(a-b-; InLu type) indicated its specificity within the CD44 (IN) antigens as they are known for suppression on RBCs from the Lu a-b-(InLu) phenotype. Molecular typing showed the exons of the hemopoietic isoform of CD44 (IN) gene with a novel homozygous missense mutation c.449G>A in exon 5 of CD44 encoding p.Arg150His amino acid substitution at the protein level. A novel HFA was named INRA by taking the first 2 letters of the IN system and the last 2 letters of the patient's first name. The ISBT had recognized INRA as a new antigen of Indian blood groups and assigned the alpha-numerical term In5. INRA-negative mutant is very rare as it was not found among 5000 donors tested serologically or by high throughput molecular approach.
Other Rare features were reported first time in India include: phenotypes like, Mg, D- -, Rhnull, I-int, In(b-), Coltonnull, ry, Emmnull, Pnull,, and S-s-U-. Of these, the discovery of Emmnull in Indian subject proved instrumental in getting the Emm recognized as a new blood group system with symbol ISBT 042. Besides, the powerful lectins like and anti-A1 and anti-H were discovered in seeds of the Indian plants, Dolichos biflorous and Momardica dioica, respectively. Also, the first-ever reported cases of interest include, anti-Leb causing HDNB, transfusion induced anti-Ina, anti-Inb causing HTR, citrate-dependent high-titer anti-H in a healthy blood donor, Streptomycin dependent panagglutinating antibody in a patient, bicarbonate anion dependent ant-”N” as a monoclonal antibody, and the spontaneous cold agglutination (SpCA) phenomenon observed among healthy donors, RHCE alleles in cis to weak D type 31 and a novel phenomenon causing blood group anomaly that mimicked Bel, a rare B antigen variant phenotype of the ABO blood group system.
The summarized account on these discoveries on Indian soil is displayed in [Table 1].
|Table 1: Chronological account of blood groups and their discoveries on Indian soil|
Click here to view
There are a total of 43 blood group systems recognized as of now. India can boast of contributing 2 blood group systems viz. Indian (ISBT023) and Emm (ISBT042). Besides, there are a number of rare phenotypes of clinical significance found in the Indian population. Supply of blood to the recipient with rare phenotypes like D- -, Rhnull, In(b-), INRA-, Coltonnull, Pnull, Emmnull, S-s-U- have been proved challenging to provide an appropriate blood unit for transfusion. The rare donor registry is a need of the hour to meet future requirements should their need arises. We have a couple of centers taking initiative in this direction yet enough has to be done to meet eventualities in our Country.
This update was presented as the ISBTI Oration Award lecture at the Annual Conference of Indian Society of Blood Transfusion and Immunohematology (Transcon 2020) held in Chennai on 27-02-2021.The author thanks Willy Albert Flegel, Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health for reviewing and offering valuable suggestions to improve the manuscript. The collaboration over decades with international laboratories, including Blood Group Reference Unit, London and International Blood Group Reference Laboratory, Bristol, UK; German Red Cross Blood Center, Ulm, Germany; National Institutes of Health, Bethesda, MD; New York Blood Center, New York, NY, and Harvard School of Medicine, Boston, MA bear immense importance in imparting their facilities while investigating the specimens presented.
| References|| |
ISBT Working Party on Blood group terminology and immunogenetics. Virtual meeting held on 10 December 2020.
Pierce SR, Merion R. Bloody Brilliant! A History Blood Groups and Blood Groupers. AABB Press, USA, 2016.
Joshi SR. Discovery of human blood groups in India. Manipal Journal of Med Sci 2018; 3(1): 33-6.
Bhende YM, Deshpande CK, Bhatia HM, Sanger RR, Race RR, Morgan WT, Watkins WM. A “new” blood group character related to the ABO system. Lancet. 1952;1(6714):903-4.
Bhatia HM, Sathe MS. Incidence of Bombay Oh phenotype and weaker variants of A and B antigens in Bombay (India). Vox Sang. 1974;27:524–32.
Gorakshakar AC, Sathe MS, Shirsat SR, Bhatia HM. Genetic studies in Ratnagiri and Sindhudurg districts of Maharashtra: Incidence of ABO, Rho (D), In a antigens, G-6-PD deficiency and abnormal hemoglobins. J Indian Anthrop Soc. 1987;22:38–46.
Sathe M, Vasantha K, Mhaisalkar P, Gorakshakar A. Distribution of Bombay (Oh) phenotype in India. J Indian Anthrop Soc. 1988;23:277-80.
Balgir RS. Identification of a rare blood group, “Bombay (Oh) phenotype,” in Bhuyan tribe of Northwestern Orissa, India. Indian Journal of Human Genetics 2007;13(3):109-13 Online DOI: 10.4103/0971-6866.38985. Access date 04/03/2021
Verma A, Vani KG, Chaitanya Kumar IS, Jothi Bai DS. Prevalence of Bombay blood group in a tertiary care hospital, Andhra Pradesh, India. Asian J Transfus Sci 2011;5:57-8.
] [Full text]
Shrivastava M, Navid S, Peethambarakshan A, Agarwal K, Khan A. Detection of rare blood group, Bombay (Oh) phenotype patients and management by acute normovolemic hemodilution. Asian J Transfus Sci 2015; 9:74-7
Joshi SR, Bhatia HM. A new red cell phenotype I- i-: Red cells lacking both I and i antigens. Vox Sang. 1979;36:34–8.
Joshi SR, Bhatia HM. I-i- phenotype in a large kindred Indian Family. Vox Sang. 1984;46:157– 60.
Badakere, SS, Joshi SR, Bhatia HM, Desai PK, Giles CM and Goldsmith KLG. Evidence for a new blood group antigen in the Indian Population (A preliminary report). Indian J Med Res 1973; 61(4):563.
Giles CM. Antithetical relationship of anti-In(a) with the Salis antibody. Vox Sang. 1975;29:73-6.
Poole J, Tilley L, Warke N, Spring F, Overbeeke, M, van der Mark-Zoet J, Ahrens N, Diane Armstrong D, Williams M, and Daniels G. Two missense mutations in the CD44 gene encode two new antigens of the Indian blood group system. Transfusion 2007;47:1306-1311.
Joshi SR, Sheladiya A, Mendapara-Dobariya KV. INRA, a new high-frequency antigen in the Indian (IN023) blood group system. Asian J Transfus Sci. 2017;11:121-3
Henny C, Thorton N, Lejon Crottet S et al. An antibody against a novel high incidence antigen in the Indian blood group system. Vox Sang 2028;113 (suppl 1):231.
Joshi SR, Senjaliya SB, Srivastava K, and Flegel WA. A resource-conserving serologic and highthroughput molecular approach to screen for blood donors with an IN:−5 phenotype Immunohematology 2020;36:129–32.
Joshi SR, Bharucha ZS, Sharma RS, Bhatia HM. The Mg blood group antigen in two Indian families. Vox Sang. 1972;22:478-80.
Badakere SS, Bhatia HM. Haemolytic disease of the newborn in a rare –D-/-D- Indian woman.Vox sang 1973;24:280.
Kulkarni S, Vasantha K, Gogri H, Parchure D, Madkaikar M, Férec C, Fichou Y. First report of Rhnull individuals in the Indian population and characterization of the underlying molecular mechanisms. Transfusion. 2017;57(8): 1944-48
Joshi SR. I-int phenotype among three individuals of a Parsi community from Mumbai, India. Immunohematology 2014, 30(1):11-13
Joshi SR. Immediate Haemolvtic Transfusion Reaction Due to Anti-Inb
Vox Sang 1992;63:232-233
Joshi SR, Wagner FF, Vasantha K, Panjwani SR, and Flegel WA. An AQP1 null allele in an Indian woman with Co(a–b–) phenotype and high-titer anti-Co3 associated with mild HDN. Transfusion. 2001;41:1273-1278.
Undevia JV, Sanghvi LD. The population genetics of the Parsis of Bombay (abstr). Int Congr Ser. 1971;233:180
Lane WJ, Aeschlimann J, Vege S, Lomas-Francis C, Burgos A, Helen H, Mah HH, Halls JBL, Ligthart P, Veldhuisen B, Shah RJ, Joshi SR, Westhoff CM. PIGG
Defines the Emm Blood Group System. ISBT Congress virtual meeting of the working Party on blood group terminology and Immunogenetics, 2020.
Shamee Shastry S, Satyamoorthy K, Acharyac KV, Reddy VR, Chenna GM, Reghunathan DD, Joshi MB. Deletion in the A4GALT Gene Associated with Rare “P null” Phenotype: The First Report from India Transfus Med Hemother 2020;47:186–9
Kanani AN, Senjaliya SB, Rajaparaa MM, Aeschlimann J, Westhoff CM, Joshi SR. P-Null Phenotype Due to a Rare Frame-Shift Mutation and with Allo-Anti-PP1Pk Causing a Severe Hemolytic Transfusion Reaction: A Case Report with Clinical Management. Transfus Med Hemothe/ DOI: 10.1159/000514499
Dara R, Jaiswal RM, et al. The first case with S-s-U- phenotype found in Indian woman (personal communication).
Bird, G. W. G. Relationship of the Blood Sub-Groups A1, A2 and A1B, A2B to Hemagglutinins Present in the Seeds of Dolichos biflorus
Joshi SR, Vasantha K,and Robb JS. An unusual antr-H lectin inhibited by milk from individuals with the Bombay phenotype. Immunoltematol. 2005;21:1-4.
Bharucha ZS, Joshi SR, Bhatia HM. Hemolytic Disease of the Newborn Due to Anti-Leb
. Vox Sang. 1981; 41: 36-9
Joshi SR, Gupta D, Choudhary RK, Choudhury N. Transfusion-induced anti-Ina
following a single unit transfusion. Transfusion 1993;33(5):444
Joshi SR. Immediate haemolytic transfusion reaction due to anti-Inb
. Vox Sang. 1992;63:232– 3.
Joshi SR. Citrate-Dependent Auto-Antibody Causing Error in Blood Grouping. Vox Sang 1997;72:229–232.
Joshi SR. Streptomycin-dependent panagglutinin causing error in forward blood grouping. Vox Sang 2001;81:55.
Iyer YS, Vasantha K, Joshi SR, Patwardhan M, Pujari V, Jadhav S, Mohanti D. A bicarbonate anion-dependent anti-'N' MoAb. Immunohematol 2004;20:59–62
Joshi SR, Naik RA, Gupte SC. Unusual spontaneous cold auto-hemagglutination phenomenon in blood units stored under blood bank condition: A retrospective analysis. Asian J Transfus Sci 2015;9:141-4.
] [Full text]
Srivastava K, Körmöczi GF, Joshi SR, Willy A Flegel WA. Two distinct RHCE alleles in cis to weak D type 31 alleles in individuals from different ethnicities. Transfusion 2018;58(10):2465-66.
Joshi SR, Kanani AN, Senjaliya SB, Rajapara MM. A novel observation on grouping anomaly: The phenomena mimicking the Bel
genetic variant of the ABO blood groups. Asian J Transfus Sci 2020; (In Press).
Source of Support: None, Conflict of Interest: None
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