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 Table of Contents  
SHORT ARTICLE
Year : 2019  |  Volume : 4  |  Issue : 1  |  Page : 79-83

The anti-Mia antibody – Report of four cases in a tertiary care hospital with review of literature


Department of Immunohematology and Blood Transfusion, Lady Hardinge Medical College, New Delhi, India

Date of Web Publication22-Apr-2019

Correspondence Address:
Dr. Shivali Sehgal
Department of Immunohematology and Blood Transfusion, Lady Hardinge Medical College, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/GJTM.GJTM_2_19

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  Abstract 


Anti – Mia antibody is antibody reacting with Mi III phenotype of the Miltenberger (Mi) subsystem. It is rarely reported in the West, however, it is common in Chinese and South East Asian populations. Very few cases have been reported in India. Here, we report 4 cases of the Anti - Mia antibody picked up on antibody screening of samples (which was performed using Asia ID-Diacell I-II-III Asia (Mia +) 3 cell panel). Patients: In all the four cases, ICT was positive. Antibody screening and Identification was done with 3 cell panel (ID-Diacell I-II-III (Asia)) and 11 cell panel (ID-DiaPanel) respectively. Antibody screening showed reaction in “Asia” cell (carrying Mia Antigen) of 3 cell panel. Antibody identification by 11 cell panel was negative ruling out antibodies of Rh, Kell, Duffy, Kidd, Lewis, P, Lutheran and MNS systems. Reaction with the “Asia” cell suggested the presence of Anti-Mia antibody which was confirmed by obtaining the same result when screening was repeated with 2 different lots of 3 cell panel. Discussion and Conclusion: The Miltenberger (Mi) subsystem comprises of a group of phenotypes of red cells that carry low frequency antigens associated with the MNSs blood group system. The Anti- Mia antibody was first described in 1951 in the serum of Mrs Miltenberger. Anti- Mia antibody is clinically significant and can cause Hemolytic disease of newborn (HDN) and mild to moderate haemolytic transfusion reactions (HTR). Most of the antibody screening and identification panels used in India are imported and represent the Western population. They do not have representation of the Mia antigen on their red cells. This leads to missing out of the Anti- Mia antibody which may cause HDN and HTR leading to significant consequences. Thus, the Mia antigen should be incorporated in our screening panels.

Keywords: Antibody, anti-Mia, cases, review


How to cite this article:
Pahuja S, Sehgal S, Sharma G, Singh M, Yadav R. The anti-Mia antibody – Report of four cases in a tertiary care hospital with review of literature. Glob J Transfus Med 2019;4:79-83

How to cite this URL:
Pahuja S, Sehgal S, Sharma G, Singh M, Yadav R. The anti-Mia antibody – Report of four cases in a tertiary care hospital with review of literature. Glob J Transfus Med [serial online] 2019 [cited 2019 Sep 16];4:79-83. Available from: http://www.gjtmonline.com/text.asp?2019/4/1/79/256739




  Introduction Top


The Miltenberger subsystem comprises a group of phenotypes of red cells that carry low-frequency antigens associated with the MNSs blood group system.[1] The Miltenberger subsystem was introduced by Cleghorn in 1966.[2] The antigen is expressed on various glycophorin variants [1] and was thought to be a cross-reactive epitope for many years; however, now, it has been shown to be a discrete antigen.[3]

The antigens of this subsystem are rare in the Western population; however, in South East Asia and China, higher frequencies are reported.[4],[5] Very limited literature is available on the prevalence of Mi a antigen in the Indian population.[1]

The anti-Mi a antibody was first described in 1951 in the serum of Mrs. Miltenberger, who had developed this antibody in response to immunization from her antigen-positive fetus.[3]

Most of the antibody screening panels used in India do not have representation of the Mi a antigen on their red cells. This leads to missing out of the anti-Mi a antibody in patients. Here, we report four cases of the anti-Mi a antibody picked up on antibody screening of samples (which was performed using Asia ID-Diacell I-II-III Asia [Mi a +] 3-cell panel).


  Case Reports Top


Case 1

A 27-year-old male, first time blood donor, came to Regional Blood Transfusion Centre, Lady Hardinge Medical College. His blood group was A negative. The donor had no history of blood transfusion in the past or any other significant history. Routine antibody screening was done with three-cell panel (ID-Diacell I-II-III [Asia]) and a positive reaction was noted with the Mi a antigen-positive cell [Figure 1] and [Table 1]. The 11-cell panel (ID DiaPanel) was put up for antibody identification, in which all cells were nonreactive with the donor's plasma. On analysis of the antigram, all the listed antigens of Rh, Kell, Duffy, Kidd, MNS, P, Lewis, Lutheran, and Xg systems could be ruled out [Table 1]. Since only one cell had the Mi a antigen in the three-cell Asia panel, we repeated the reaction of patients' plasma with three different lots of screening cells (having Mi a antigen) for confirmation. Reaction of the donor's serum with three different Mi a-positive cells confirmed the specificity for anti-Mi a antibody. However, the test for Mi a antigen on the donor's cells could not be performed due to nonavailability of anti-Mi a antiserum. Dithiothreitol (DTT) treatment of the donor's serum was done, and the reaction in the Mi a-positive cell of the screening panel was abolished. This suggested that the antibody was immunoglobulin M (IgM) and not IgG and therefore probably naturally occurring.
Figure 1: Gel card showing 4+ reaction in the third cell during antibody screening (Case 1)

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Table 1: Antegram showing antibody screening results and antibody identification results of the four cases

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Case 2 and Case 3

Two thalassemic patients (17-year-old-male and 11-year-old female) enrolled in Thalassemia Day Care Centre of Kalawati Saran Children's Hospital were on regular blood transfusions as per the partial better-matched policy.

In antibody screening by three-cell panel, positive reaction was noted in the Mi a-positive cell of the three-cell Asia panel [Table 1]. Specificity was confirmed by repeating the test with two other Mi a-positive cells of different lots of the three-cell Asia panel. The reaction in all cells of 11-cell panel was negative [Table 1].

Case 4

An adult female patient with a history of chronic liver disease was admitted in the medicine ward of the hospital. She had hyperbilirubinemia and gave a history of multiple blood transfusions. The indirect Coombs test was positive and the Mi a cell of the three-cell panel gave a positive reaction [Table 1]. Reaction in all 11 cells of 11-cell panel was negative. Specificity was confirmed by repeating the test with two other Mi a-positive cells of different lots of the three-cell Asia panel.

The DTT treatment could not be done in the second, third, and fourth case.


  Discussion Top


The Miltenberger subsystem or the Mi subsystem consists of a total of 11 phenotypes.[6] The Mi a antigen is present on red cells with several Miltenberger phenotypes (Mi I, Mi II, Mi III, Mi IV, Mi VI, and Mi X).[7]

The best-known example of Mi a phenotype is created by the hybrid gene responsible for the GP Mur (Mi III) phenotype. The Mur antigen is rare in people of European and African ethnicity; it has a prevalence of around 7% in Chinese and 10% in Thai population. In Hong Kong and Taiwan, anti-Mur is the most common antibody after anti-A and anti-B.[3] Therefore, the AABB recommends that red cells for antibody detection should include a Mur-positive sample, particularly in South East Asia.[6]

The term anti-Mi a describes antibodies which react with the Mi III phenotype. The anti-Mi a antibody is rarely reported in Western literature. The first monoclonal anti-Mi a was reported by Chen et al.[6] – confirming the existence of Mi a antigen. Kim et al. detected a naturally occurring anti-Mi a antibody in a 16-year-old Korean man on routine screening.[8]

Anti-Mi a antibody is commonly found in China and South East Asia. The prevalence of anti-Mi a antibodies was found to be 0.28% in Chinese blood donors in Taiwan,[9] 0.34% in Chinese blood donors in Hong Kong,[10] and 0.2% in Thai blood donors.[11] In another study, anti-Mi a was one of the five most common alloantibodies found in the Thai population – found in 21.1% of the patients and 7% of donors and 15.2% of the total population.[12] Srijinda et al. performed antibody screening in Thai population and concluded that anti-Mi a was the most common single alloantibody (65.16%).[4] Anti-Mi a antibody was the third most common antibody detected in patients in three of the major ethnic groups residing in Malaysia – Chinese, Malays, and Indians.[13] Anti-Mi a was also detected frequently in the Korean population.[14]

Most of the antibodies detected with Mi a cells are IgM and tend to react best at cold temperatures. However, IgG antibodies react best at 37°C and are clinically relevant.

The anti-Mi a antibody has been implicated in causing hemolytic disease of newborn (HDN) and hemolytic transfusion reactions (HTRs).[9],[15],[16] A case of neonatal isoimmune hemolytic disease due to anti-Mi a antibody has been reported in Korea.[17] Severe form of HDN, hydrops fetalis, has also been reported due to anti-Mi a antibody. The potency of the antibody was due to repeated immunization of the mother during some of her previous pregnancies.[18]

Anti-Mi a antibody is frequently reported in studies on antenatal alloimmunization. Lee et al. evaluated that anti-Mi a was the commonest antibody found in antenatal Chinese women (57.6%).[5] In Hong Kong, the antibody was found in 0.46% of pregnant women.[10]

It has been frequently observed that even after negative antibody screening of recipients, cross-match is incompatible. This reflects that we are probably missing out on some antibodies which are not represented in the panels we use. Varghese et al. analyzed the red cell alloimmunization among antenatal women in a tertiary care hospital in South India and reported nonspecific antibodies (specificity not identified) were present in 37% of females.[19] Considering the very varied phenotypic profile of our country (therefore the very varied antigenic distribution), we require indigenous cell panels which would adequately represent the red cell phenotype of our country.

Very little literature is available on the prevalence of Mi a antigen and anti-Mi a antibody from India. Only a single study with a small sample size has reported the incidence of Mi a antigen in Indian donors.[1] We have not come across any published case of anti-Mi a antibody from India.

Due to the expansion of medical tourism in India and influx of patients from Asian and African countries, the exact incidence of anti-Mi a antibody in our population needs to be evaluated. Further, large-scale studies are needed to evaluate the red cell phenotype of the Indian population and to prepare our Indigenous cell panels.


  Conclusion Top


Since most of the antibody screening and identification panels available in India are imported and represent the Western population, this leads to missing out of antibodies against the Indigenous antigens. Missing out on clinically significant antibodies such as anti-Mi a can lead to significant consequences (HDN and HTR). Therefore, Mi a-positive red cells should be routinely incorporated in our indigenous antibody screening and identification panels.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Makroo RN, Bhatia A, Chowdhry M, Rosamma NL, Karna P. Frequency of Mi(a) antigen: A pilot study among blood donors. Indian J Med Res 2016;143:633-5.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
Cleghorn TE. A memorandum on the Miltenberger blood groups. Vox Sang 1966;11:219-22.  Back to cited text no. 2
    
3.
Technical Manual. 19th ed. Bethesda: American Association of of Blood Banks; 2017.  Back to cited text no. 3
    
4.
Srijinda S, Bosuwan S, Nuanin C, Suwanasophon C. Anti-Mi a and Anti-E: The most common clinically significant red cell alloantibodies in patients at Phramongkutklao Hospital. R Thai Army Med J 2017;70:65-70.  Back to cited text no. 4
    
5.
Lee CK, Ma ES, Tang M, Lam CC, Lin CK, Chan LC, et al. Prevalence and specificity of clinically significant red cell alloantibodies in Chinese women during pregnancy – A review of cases from 1997 to 2001. Transfus Med 2003;13:227-31.  Back to cited text no. 5
    
6.
Chen V, Halverson G, Wasniowska K, Lisowska E, Chen J, Moulds M, et al. Direct evidence for the existence of Miltenberger antigen. Vox Sang 2001;80:230-3.  Back to cited text no. 6
    
7.
Tippett P, Reid ME, Poole J, Green CA, Daniels GL, Anstee DJ, et al. The Miltenberger subsystem: Is it obsolescent? Transfus Med Rev 1992;6:170-82.  Back to cited text no. 7
    
8.
Kim HH, Park TS, Oh SH, Lee EY, Son HC. Naturally occurring Anti – Mi a in a 16 year old Korean man: A case study and a review of literature. Korean J Lab Med 2004;24:146-8.  Back to cited text no. 8
    
9.
Broadberry RE, Lin M. The incidence and significance of anti-”Mia” in Taiwan. Transfusion 1994;34:349-52.  Back to cited text no. 9
    
10.
Mak KH, Banks JA, Lubenko A, Chua KM, Torres de Jardine AL, Yan KF, et al. A survey of the incidence of Miltenberger antibodies among Hong Kong Chinese blood donors. Transfusion 1994;34:238-41.  Back to cited text no. 10
    
11.
Chandanayingyong D, Bejrachandra S. Studies on Anti- Mi a and Mi III complex. Vox Sang 1975;29:311-5.  Back to cited text no. 11
    
12.
Promwong C, Siammai S, Hassarin S, Buakaew J, Yeela T, Soisangwan P, et al. Frequencies and specificities of red cell alloantibodies in the Southern Thai population. Asian J Transfus Sci 2013;7:16-20.  Back to cited text no. 12
[PUBMED]  [Full text]  
13.
Prathiba R, Lopez CG, Usin FM. The prevalence of GP Mur and anti-”Mia” in a tertiary hospital in peninsula Malaysia. Malays J Pathol 2002;24:95-8.  Back to cited text no. 13
    
14.
Sung NH, Jeon TY, Lee EY, Chung JS, Cho GJ, Kim HH. Prevalence and specificity of unexpected antibody using antibody screening test including Dia and Mi a cells. Korean J Lab Med 2005;25:340-6.  Back to cited text no. 14
    
15.
Poole J, King MJ, Mak KH, Liew YW, Leong S, Chua KM. The MiIII phenotype among Chinese donors in Hong Kong: Immunochemical and serological studies. Transfus Med 1991;1:169-75.  Back to cited text no. 15
    
16.
Chiewsilp P, Wiratkasem Y, Sae-huan C. Delayed haemolytic transfusion reaction due to anti-Mi a. Thai J Hematol Transfus Med 1996;6:289-90.  Back to cited text no. 16
    
17.
Park SW, Park JH, Kim Y, You JH, Cho HM, Kim EY, et al. A case of neonatal isoimmune haemolytic disease due to anti-Mi a antibody with massive fetomaternal hemorrhage. Korean J Perinatol 2013;24:310.  Back to cited text no. 17
    
18.
Lin M, Broadberry RE. An intravascular haemolytic transfusion reaction due to anti – Mi a in Taiwan. Vox Sang 1975;28:152-5  Back to cited text no. 18
    
19.
Varghese J, Chacko MP, Rajaiah M, Daniel D. Red cell alloimmunization among antenatal women attending a tertiary care hospital in South India. Indian J Med Res 2013;138:68-71.  Back to cited text no. 19
[PUBMED]  [Full text]  


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