Erythroid anion transport, nitric oxide, and blood pressure.

Glycophorin A and glycophorin B are structural membrane glycoproteins bound in the band 3 multiprotein complexes on human red blood cells (RBCs). Band 3 is an erythroid-specific anion exchanger (AE1). AE1-mediated HCO3 - transport provides the substrate for the enzyme-catalyzed conversion HCO3 - (aq) ⇌ CO2(g), which takes place inside the RBCs. Bicarbonate transport via AE1 supports intravascular acid-base homeostasis and respiratory excretion of CO2. In the past decade, we conducted several comparative physiology studies on Taiwanese people having the glycophorin variant GPMur RBC type (which accompanies greater AE1 expression). We found that increased anion transport across the erythrocyte membrane not only enhances gas exchange and lung functions but also elevates blood pressure (BP) and reduces nitric oxide (NO)-dependent vasodilation and exhaled NO fraction (FeNO) in healthy individuals with GP.Mur. Notably, in people carrying the GPMur blood type, the BP and NO-dependent, flow-mediated vasodilation (FMD) are both more strongly correlated with individual hemoglobin (Hb) levels. As blood NO and nitrite (NO2 -) are predominantly scavenged by intraerythrocytic Hb, and NO2 - primarily enters RBCs via AE1, could a more monoanion-permeable RBC membrane (i.e., GPMur/increased AE1) enhance NO2 -/NO3 - permeability and Hb scavenging of NO2 - and NO to affect blood pressure? In this perspective, a working model is proposed for the potential role of AE1 in intravascular NO availability, blood pressure, and clinical relevance.

Development of Mia Phenotyping Using Paper-Based Device.

The MNS7 (Mia) blood group antigen is found at a different prevalence among different ethnic groups. Anti-Mia can cause hemolytic disease of the fetus and newborn (HDFN) and both acute- and delayed-type hemolytic transfusion reactions (HTR). Mia typing should be performed in donors to prevent life-threatening hemolytic transfusion reactions. The gel card and standard tube methods still need specialized equipment, centrifugation, and expertise for result interpretation. We used a novel paper-based analytical device (PAD) pre-coated with monoclonal IgM anti-Mia for Mia phenotyping. We measured grey pixel intensity in blood typing results for interpretation processing using OpenCV at the sample (SP) and elution parts (EP); furthermore, we used the SP: EP ratio and F-score as analysis criteria. We typed 214 blood EDTA samples with PAD-Mia and then compared with gel card results for setting an analysis criterion. We observed 100% sensitivity, specificity, and accuracy when we applied the SP: EP ratio and F-score with the optimal criterion (1.07 and 0.17 for SP: EP ratio and F-score, respectively). The validation of PAD-Mia typing for blood donor samples (n = 150) via F-score gave 100% sensitivity and specificity when compared with the gel card method; therefore, we argue that PAD-Mia typing can be used for Mia phenotyping without sero-centrifugation. Moreover, to study the correlation between genotype and phenotype, PCR-SSP was performed to identify GYP(B-A-B) hybrids. The results revealed that all Mia+ blood samples gave a positive with GP. Hut, GP. HF, GP. Mur, GP. Hop, and GP. Bun. Results of the gel card method and PCR-SSP were concordant. Hence, using PAD-Mia typing in blood donors would be helpful for creating a phenotype database of blood donors for reducing alloimmunization risks.

A Balance between Transmembrane-Mediated ER/Golgi Retention and Forward Trafficking Signals in Glycophorin-Anion Exchanger-1 Interaction.

Anion exchanger-1 (AE1) is the main erythroid Cl-/HCO3- transporter that supports CO2 transport. Glycophorin A (GPA), a component of the AE1 complexes, facilitates AE1 expression and anion transport, but Glycophorin B (GPB) does not. Here, we dissected the structural components of GPA/GPB involved in glycophorin-AE1 trafficking by comparing them with three GPB variants-GPBhead (lacking the transmembrane domain [TMD]), GPBtail (mainly the TMD), and GP.Mur (glycophorin B-A-B hybrid). GPB-derived GP.Mur bears an O-glycopeptide that encompasses the R18 epitope, which is present in GPA but not GPB. By flow cytometry, AE1 expression in the control erythrocytes increased with the GPA-R18 expression; GYP.Mur+/+ erythrocytes bearing both GP.Mur and GPA expressed more R18 epitopes and more AE1 proteins. In contrast, heterologously expressed GPBtail and GPB were predominantly localized in the Golgi apparatus of HEK-293 cells, whereas GBhead was diffuse throughout the cytosol, suggesting that glycophorin transmembrane encoded an ER/Golgi retention signal. AE1 coexpression could reduce the ER/Golgi retention of GPB, but not of GPBtail or GPBhead. Thus, there are forward-trafficking and transmembrane-driven ER/Golgi retention signals encoded in the glycophorin sequences. How the balance between these opposite trafficking signals could affect glycophorin sorting into AE1 complexes and influence erythroid anion transport remains to be explored.

Influence of hemoglobin on blood pressure among people with GP.Mur blood type☆.

BACKGROUND/PURPOSE: GP.Mur is a clinically important red blood cell (RBC) type. GP.Mur and band 3 interact on the RBCs. We previously observed that healthy adults with GP.Mur type present slightly higher blood pressure (BP). Because band 3 and Hb comodulate nitric oxide (NO)-dependent vasodilation and hemoglobin (Hb) is positively associated with BP, we aimed to test whether these could contribute to higher BP in GP.Mur+ people. METHODS: We recruited 989 non-elderly adults (21% GP.Mur) free of catastrophic illness and not on cardiovascular or anti-hypertensive medication. Their body indices, blood lab data and lifestyle data were collected for analyses of potential BP-related factors (BMI, age, smoking, Hb, and GP.Mur). RESULTS: BMI and age remained the most significant contributors to BP. GP.Mur slightly increased systolic BP (SBP). The direct correlation between Hb and BP was only found in Taiwanese non-anemic men, not women. After age and BMI adjusted, we estimated an increase of 1.8 mmHg and 2.6 mmHg of SBP by 1 g/dL Hb among men without and with GP.Mur type, respectively. Hb was generally lower among people expressing GP.Mur, which likely limited their larger impact on BP. CONCLUSION: GP.Mur contributed to BP in both Hb-dependent and Hb-independent fashion. A pronounced impact of hemoglobin on BP likely requires sufficient Hb, as GP.Mur increased the sensitivity of SBP to Hb only in non-anemic Taiwanese men, and not in Taiwanese women or anemic men. The mechanism through which GP.Mur affected BP independent of Hb is unknown.

Frequencies of glycophorin variants and alloantibodies against Hil and MINY antigens in Japanese.

BACKGROUND AND OBJECTIVES: Antigens of the MNS blood group system are expressed on the red blood cell (RBC) membrane on glycophorin A (GPA) and glycophorin B (GPB) or on hybrid molecules of GPA and GPB. This study investigated the distribution of glycophorin variants and alloantibodies against Hil and MINY among Japanese individuals. METHODS: Mi(a+) or Hil+ RBCs were screened using an automated blood grouping machine (PK7300) with monoclonal anti-Mia or polyclonal anti-Hil. Glycophorin variants were defined by serology with monoclonal antibodies against Mia , Vw, MUT and Mur, and polyclonal antibodies against Hil, MINY and Hop + Nob (KIPP). The glycophorin variants were further confirmed by immunoblotting and Sanger sequencing. Alloanti-Hil and alloanti-MINY in the plasma were screened using GP.Hil RBCs in an antiglobulin test. The specificity of anti-Hil or anti-MINY was assessed using GP.Hil (Hil+MINY+) and GP.JL (Hil-MINY+) RBCs. RESULTS: The GP.HF, GP.Mur, GP.Hut, GP.Vw, GP.Kip and GP.Bun frequencies in 1 005 594 individuals were 0·0357%, 0·0256%, 0·0181%, 0·0017%, 0·0009% and 0·0007%, respectively. GP.Hil was found in as four of the 13 546 individuals (0·0295%). Of 137 370 donors, 10 had anti-Hil (0·0073%) and three had anti-MINY (0·0022%). CONCLUSIONS: Glycophorin variants were relatively rare in Japanese individuals, with the major variants being GP.HF (0·0357%), GP.Hil (0·0295%) and GP.Mur (0·0256%). Only one example of anti-MINY was previously reported, but we found three more in this study.

Different Involvement of Band 3 in Red Cell Deformability and Osmotic Fragility-A Comparative GP.Mur Erythrocyte Study.

GP.Mur is a clinically important red blood cell (RBC) phenotype in Southeast Asia. The molecular entity of GP.Mur is glycophorin B-A-B hybrid protein that promotes band 3 expression and band 3-AQP1 interaction, and alters the organization of band 3 complexes with Rh/RhAG complexes. GP.Mur+ RBCs are more resistant to osmotic stress. To explore whether GP.Mur+ RBCs could be structurally more resilient, we compared deformability and osmotic fragility of fresh RBCs from 145 adults without major illness (47% GP.Mur). We also evaluated potential impacts of cellular and lipid factors on RBC deformability and osmotic resistivity. Contrary to our anticipation, these two physical properties were independent from each other based on multivariate regression analyses. GP.Mur+ RBCs were less deformable than non-GP.Mur RBCs. We also unexpectedly found 25% microcytosis in GP.Mur+ female subjects (10/40). Both microcytosis and membrane cholesterol reduced deformability, but the latter was only observed in non-GP.Mur and not GP.Mur+ normocytes. The osmotic fragility of erythrocytes was not affected by microcytosis; instead, larger mean corpuscular volume (MCV) increased the chances of hypotonic burst. From comparison with GP.Mur+ RBCs, higher band 3 expression strengthened the structure of RBC membrane and submembranous cytoskeletal networks and thereby reduced cell deformability; stronger band 3-AQP1 interaction additionally supported osmotic resistance. Thus, red cell deformability and osmotic resistivity involve distinct structural-functional roles of band 3.

Frequency of Mia (MNS7) and Classification of Mia-Positive Hybrid Glycophorins in an Australian Blood Donor Population.

BACKGROUND: MNS blood group system genes GYPA and GYPB share a high degree of sequence homology and gene structure. Homologous exchanges between GYPA and GYPB form hybrid genes encoding hybrid glycophorins GP(A-B-A) and GP(B-A-B). Over 20 hybrid glycophorins have been characterised. Each has a distinct phenotype defined by the profile of antigens expressed including Mia. Seven hybrid glycophorins carry Mia and have been reported in Caucasian and Asian population groups. In Australia, the population is diverse; however, the prevalence of hybrid glycophorins in the population has never been determined. The aims of this study were to determine the frequency of Mia and to classify Mia-positive hybrid glycophorins in an Australian blood donor population. METHOD: Blood samples from 5,098 Australian blood donors were randomly selected and screened for Mia using anti-Mia monoclonal antibody (CBC-172) by standard haemagglutination technique. Mia-positive red blood cells (RBCs) were further characterised using a panel of phenotyping reagents. Genotyping by high-resolution melting analysis and DNA sequencing were used to confirm serology. RESULT: RBCs from 11/5,098 samples were Mia-positive, representing a frequency of 0.22%. Serological and molecular typing identified four types of Mia-positive hybrid glycophorins: GP.Hut (n = 2), GP.Vw (n = 3), GP.Mur (n = 5), and 1 GP.Bun (n = 1). GP.Mur was the most common. CONCLUSION: This is the first comprehensive study on the frequency of Mia and types of hybrid glycophorins present in an Australian blood donor population. The demographics of Australia are diverse and ever-changing. Knowing the blood group profile in a population is essential to manage transfusion needs.

A case report on anti-Mia antibody in a multi-transfused patient from India.

GP.Mur antigen belongs to the MNSs system and the corresponding antibody is called as anti-Mia antibody. Anti-Mia antibody is a clinically significant antibody capable of causing haemolytic disease of the new born (HDFN) and intravascular haemolytic transfusion reactions. Literature on anti-Mia antibody from India is very limited. We report here a case of anti-Mia antibody in a multi-transfused patient from India.

The MNS glycophorin variant GP.Mur affects differential erythroid expression of Rh/RhAG transcripts.

BACKGROUND: The band 3 macrocomplex (also known as the ankyrin-associated complex) on the red cell membrane comprises two interacting subcomplexes: a band 3/glycophorin A subcomplex, and a Rh/RhAG subcomplex. Glycophorin B (GPB) is a component of the Rh/RhAG subcomplex that is also structurally associated with glycophorin A (GPA). Expression of glycophorin B-A-B hybrid GP.Mur enhances band 3 expression and is associated with lower levels of Rh-associated glycoprotein (RhAG) and Rh polypeptides. The goal of this study was to determine whether GP.Mur influenced erythroid Rh/RhAG expression at the transcript level. MATERIALS AND METHODS: GP.Mur was serologically determined in healthy participants from Taitung County, Taiwan. RNA was extracted from the reticulocyte-enriched fraction of peripheral blood, followed by reverse transcription and quantitative PCR for RhAG, RhD and RhCcEe. RESULTS: Quantification by real-time PCR revealed significantly fewer RhAG and RhCcEe transcripts in the reticulocytes from subjects with homozygous GYP*Mur. Independent from GYP.Mur, both RhAG and RhD transcript levels were threefold or higher than that of RhCcEe. Also, in GYP.Mur and the control samples alike, direct quantitative associations were observed between the transcript levels of RhAG and RhD, but not between that of RhAG and RhCcEe. CONCLUSION: Erythroid RhD and RhCcEe were differentially expressed at the transcript levels, which could be related to their different degrees of interaction or sensitivity to RhAG. Further, the reduction or absence of glycophorin B in GYP.Mur erythroid cells affected transcript expressions of RhAG and RhCcEe. Thus, GPB and GP.Mur differentially influenced Rh/RhAG expressions prior to protein translation.

Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO2 transport.

Human CO2 respiration requires rapid conversion between CO2 and HCO3- Carbonic anhydrase II facilitates this reversible reaction inside red blood cells, and band 3 [anion exchanger 1 (AE1)] provides a passage for HCO3- flux across the cell membrane. These 2 proteins are core components of the CO2 transport metabolon. Intracellular H2O is necessary for CO2/HCO3- conversion. However, abundantly expressed aquaporin 1 (AQP1) in erythrocytes is thought not to be part of band 3 complexes or the CO2 transport metabolon. To solve this conundrum, we used Förster resonance energy transfer (FRET) measured by fluorescence lifetime imaging (FLIM-FRET) and identified interaction between aquaporin-1 and band 3 at a distance of 8 nm, within the range of dipole-dipole interaction. Notably, their interaction was adaptable to membrane tonicity changes. This suggests that the function of AQP1 in tonicity response could be coupled or correlated to its function in band 3-mediated CO2/HCO3- exchange. By demonstrating AQP1 as a mobile component of the CO2 transport metabolon, our results uncover a potential role of water channel in blood CO2 transport and respiration.-Hsu, K., Lee, T.-Y., Periasamy, A., Kao, F.-J., Li, L.-T., Lin, C.-Y., Lin, H.-J., Lin, M. Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO2 transport.

Selection of GP. Mur antigen-negative RBC for blood recipients with anti-'Mia ' records decreases transfusion reaction rates in Taiwan.

OBJECTIVES: To evaluate the clinical significance of GP. Mur antigen-negative blood selection for transfusion in patients with anti-'Mia ' records. BACKGROUND: The GP. Mur RBC phenotype is prevalent (7·3%) in Taiwan. Antibodies against GP. Mur (anti-'Mia ') are identified in 1·24% of our population, and anti-'Mia ' screening using GP. Mur RBC has been routine for Taiwan's blood banks. However, due to the lack of commercial antibodies, only cross-matching was used to prevent transfusion of GP. Mur-positive blood to patients with anti-'Mia ' in most hospitals. There is still a risk of GP. Mur-positive RBC exposure and subsequent anti-'Mia '-related transfusion reactions. METHODS: Since February 2014, GP. Mur antigen-negative RBCs identified by reaction with anti-'Mia '-positive serum were selected for blood recipients with anti-'Mia ' records. The transfusion reactions between January 2013 and January 2014 were compared with those that occurred between February 2014 and July 2015. RESULTS: The transfusion reaction rate was significantly higher in anti-'Mia '-positive blood recipients compared to total subjects receiving an RBC transfusion before GP. Mur-negative donor RBC selection. After antigen-negative RBC selection, the transfusion reaction frequency in subjects with anti-'Mia ' became similar to total blood recipients. IgG form anti-'Mia ' antibodies were present in all cases of probable anti-'Mia '-related transfusion reactions. The time required for anti-'Mia ' boosting after transfusion was around 4-21 days. CONCLUSION: Selection of GP. Mur-negative RBC for transfusion to patients with anti-'Mia ' records could decrease the rate of transfusion reaction and antibody boosting. This procedure should be incorporated into blood bank routines in areas where anti-'Mia ' is prevalent.

Colorimetric Detection by Gold Nanoparticle DNA Probes for Miltenberger Series (GP.Mur, GP.Hop, and GP.Bun) Identification.

BACKGROUND: Miltenberger (Mi) series are the collective glycophorin hybrids in the MNS blood group system. Mi series are composed of several subtypes, for examples, GP.Mur, GP.Hop, and GP.Bun. The incompatibility of Mi series blood transfusion poses the risk of hemolysis. Due to the lack of standard antibodies for Mi series blood typing, colorimetric gold nanoparticle (AuNP) DNA probes were therefore explored for Mi series identification. METHODS: AuNPs were synthesized and conjugated to an RvB (test) probe and an RvA2 (control) probe. Each of the AuNP DNA probes was tested against the amplified products of Mi(+) (GP.Mur/Hop/Bun), Mi(-), and the blank (no amplified product). The change in color was observed by visual inspection and UV-Vis spectroscopy. RESULTS: The amplified product of the Mi(+) sample retained the color on both probes (test+/control+). The amplified product of the Mi(-) sample retained the color only on the control probe (test-/control+) and the amplified product of the blank turned clear on both probes (test-/control-). The results by optical density absorbance measurement were concordant with the results by visual inspection. Both probes were validated with the amplified products of the ten Mi(+) and ten Mi(-) samples. All of the samples were correctly identified. CONCLUSION: AuNP DNA probes (RvB and RvA2) could be applied to distinguish the amplified products of Mi(+), Mi(-), and the blank by visual inspection and/or OD absorbance measurement.

Mur (MNS 10) screening with a novel loop-mediated isothermal amplification assay in Zhongshan, China.

BACKGROUND: The distribution of the Mur blood group antigen is 5-7% in the south of China, and a much higher prevalence is observed in some areas of the region. Anti-Mur can cause hemolytic disease of the newborn and severe transfusion reactions. OBJECTIVES: Genetic testing is more ideal than conventional serological tests because antibodies for detection are usually not available. METHODS: In this study, a novel loop-mediated isothermal amplification (LAMP) assay for the detection of Mur blood group antigen was established. RESULTS: Fifteen of 275 (5·5%) samples were confirmed by LAMP as Mur antigen positive. All the Mur antigen-positive samples were GP.Mur subtype which was confirmed with sequencing. CONCLUSION: The LAMP method has identical results with conventional serology method but more suitable for large-scale screening.

Miltenberger blood group typing by real-time polymerase chain reaction (qPCR) melting curve analysis in Thai population.

OBJECTIVES: To develop reliable and convenient methods for Miltenberger (Mi(a) ) blood group typing. AIM: To apply real-time polymerase chain reaction (qPCR) melting curve analysis to Mi(a) blood group typing. BACKGROUND: The Mi(a) blood group is the collective set of glycophorin hybrids in the MNS blood group system. Mi(a+) blood is common among East Asians and is also found in the Thai population. Incompatible Mi(a) blood transfusions pose the risk of life-threatening haemolysis; therefore, Mi(a) blood group typing is necessary in ethnicities where the Mi(a) blood group is prevalent. METHODS/MATERIALS: One hundred and forty-three blood samples from Thai blood donors were used in the study. The samples included 50 Mi(a+) samples and 93 Mi(a-) samples, which were defined by serology. The samples were typed by Mi(a) typing qPCR, and 50 Mi(a+) samples were sequenced to identify the Mi(a) subtypes. Mi(a) subtyping qPCR was performed to define GP.Mur. Both Mi(a) typing and Mi(a) subtyping were tested on a conventional PCR platform. RESULTS: The results of Mi(a) typing qPCR were all concordant with serology. Sequencing of the 50 Mi(a+) samples revealed 47 GP.Mur samples and 3 GP.Hop or Bun samples. Mi(a) subtyping qPCR was the supplementary test used to further define GP.Mur from other Mi(a) subtypes. Both Mi(a) typing and Mi(a) subtyping performed well using a conventional PCR platform. CONCLUSION: Mi(a) typing qPCR correctly identified Mi(a) blood groups in a Thai population with the feasibility of Mi(a) subtype discrimination, and Mi(a) subtyping qPCR was able to further define GP.Mur from other Mi(a) subtypes.

Dissecting alternative splicing in the formation of Miltenberger glycophorin subtype III (GYP.Mur).

BACKGROUND AND OBJECTIVES: Miltenberger subtype III (Mi.III, GP.Mur) is one of the most important red cell phenotypes in the fields of transfusion in South-East Asia. GP.Mur is believed to evolve from homologous gene recombination events between glycophorin A (GYPA) and glycophorin B (GYPB). GYP.Mur differs from GYPB in only seven nucleotides dispersed near the region of 3' exon 3 of GYP.Mur. The goal of this study was to dissect how these nucleotide variants affected splicing of exon 3. MATERIALS AND METHODS: We first designed two minigene constructs: one containing GYP.Mur from exon 2 to exon 4 and the other containing GYPB in the same region. To test how these nucleotide variations between GYP.Mur and GYPB affected the splicing, a repertoire of the GYP.Mur-like minigene constructs with different point mutations were created. These minigene variants were evaluated for their abilities to induce splicing of exon 3 using a heterologous expression system. RESULTS: (1) GYP.Mur minigene expressed exons 2, 3 and 4, whereas GYPB minigene expressed only exon 2 and exon 4. (2) The single nucleotide alteration at the position of the 5' splice site of glycophorin intron 3 reversed the splicing decision. (3) The nucleotide variations between GYP.Mur and GYPB other than that at the 5' splice site showed very little or no effect on splicing of exon 3. CONCLUSION: Splicing of the glycophorin B-A-B hybrids (GYP.Mur and GYP.BUN) and unsplicing of GYPB follow the GU-AG rule strictly.

A Case of Neonatal Isoimmune Hemolytic Disease due to Anti-Mi(a) Antibody with Massive Fetomaternal Hemorrhage / 대한주산의학회잡지

Authors experienced a newborn treated with severe anemia transferred to our hospital due to pulselessness and apnea shortly after birth. Laboratory analysis of the blood on admission revealed hemoglobin 3.1 g/dL, reticulocyte 11.0%. Kleihauer-Betke test for fetal hemoglobin from maternal blood was seen Hgb F 7%, then we suggested almost 180 ml fetomaternal hemorrhage. But, anemia was not improved despite repeated packed RBC transfusion. So, we evaluated the other cause of intractable anemia. The results were as follows; the Coombs' test was positive. The antibody identification test using mother's serum revealed anti-Mia antibody. The patient improved with supportive treatment, but got hypoxic brain injury due to massive fetomaternal hemorrhage. At day 29, the infant was doing well and was discharged. We report a case of neonatal isoimmune hemolytic disease due to anti-Mia with massive fetomaternal hemorrhage with a brief review of the related literatures.

A case of Hemolytic Disease of the Newborn due to Anti-Mi a Antibody / 대한수혈학회지

We report a case of hemolytic disease of the newborn caused by anti-Mia (Miltenberger) antibody. Full term male infant was admitted due to hyperbilirubinemia on second day of life. Total serum bilirubin level was 8.6 mg/dL at 12 hours of age and 12.3 mg/dL at 24 hours of age. The blood group of patient and his mother were both RhD positive B type. Direct antiglobulin test was strongly positive in the patient, and testing of maternal serum and patient's serum against a red cell panel including cells known to carry the antigenic determinants of some Miltenberger phenotypes revealed the presence of anti-Mia . Testing of paternal red cells and patient's red cell against anti-Mia serum revealed positive reaction. This report documents the first case of hemolytic disease of the newborn due to anti-Mi a in Korea.

Naturally-occurring Anti-Mia(a) in a 16-year-old Korean Man: A Case Study and a Review of the Literature / 대한진단검사의학회지

We report a case of naturally-occurring anti-Miltenberger (anti-Mia(a)) antibody in a 16-year-old man who had never been transfused before. During an operation for a trauma he received 2 units of packed red blood cells. He was negative on an antibody screening test, but positive a week after the surgery when an extended screening test was conducted using blood cells positive for Miltenberger III (Mi.III) phenotype. The Mi.III phenotype is a low incidence antigen among Caucasians, however, it is reported to be relatively high in incidence among people in South-East Asia. Anti-Mia(a) antibodies are clinically significant antibodies that cause hemolytic transfusion reactions (HTRs) and hemolytic disease of the newborns (HDNs). In addition, anti-Mia(a) has a high rate of incidence among Thais, Taiwanese, and Hong Kong Chinese. There has been no particular report on Koreans regarding the incidence of this antibody, it would therefore require further research on the Mi.III phenotype and anti-Mia(a).