Alloimmunity to Erythrocytes in Patients during Pregnancy in South Korea and Japan; Recent Results from a Cooperative International Study of Alloimmunity to Antigen Diversity in Asian Populations

Introduction: Pregnancy sometimes leads to the production of irregular erythrocyte alloantibodies (Abs). Although several investigations have been carried out in the U.S. and European countries there are few international collaborative studies on irregular erythrocyte Abs during pregnancy. Asia has a wide multiethnic population and is therefore ideal for studying diversity among ethnic groups related to transfusion medicine. However, the frequency and specificity of antigens and antibodies to erythrocytes as well as their detection is not well characterized. Therefore, the Alloimmunity to Antigen Diversity in Asian Populations Study Group was established in 2008, with the aim of studying erythrocyte alloimmunity among Asians. Here, we report similarities and differences of irregular erythrocyte Abs in pregnant patients from South Korea and Japan.

Materials and Methods: Altogether, 21 institutions in South Korea and 59 in Japan participated in this study. We surveyed methods employed for screening and identifying irregular erythrocyte Abs. The frequencies of irregular Abs to D, C, c, E, e, f, Ce, P₁, M, N, S, s, Mi^a, Le^a, Le^b, Jk^a, Jk^b, Jk3, Fy^a, Fy^b, K, k, Kp^a, Kp^b, Js^a, Js^b, Di^a, Di^b, Lu^a, Lu^b, Xg^a and H were investigated. If a case was analyzed multiple times, it was counted only once. Multiple antibodies detected in the same patient were counted separately. The number of patients who were pregnant at the time (pregnant patients) of the irregular erythrocyte Abs investigation was counted and compared to female patients who were not pregnant (non-pregnant female patients). Because of differences observed in anti-D Ab frequency, we investigated the number of anti-D cases in pregnant patients who received anti-D immunoglobulin, and compared it with the number of alloimmunized anti-D cases among 26 institutions in Japan from 2011 to 2013. The study was accepted with IRB in our university (#22-193, #25-252).

Results: Different irregular erythrocyte Abs screening methods have been adopted at the various institutions involved in this study. The gel column method was used at 46% of institutions in South Korea and 19% of institutions in Japan, whereas the bead column method was used at 43% of institutions in South Korea and 61% of institutions in Japan. The indirect antiglobulin test (IAT) has been adopted at all institutions in both countries. The enzyme methods have been adopted at 58% of institutions in South Korea and 81% of institutions in Japan. Among more than 1.8 million patients were analyzed, antibodies were totally detected in 16,438 patients (3,525 in South Korea; 12,913 in Japan). The number of female patients was 2,113 in South Korea and 7,595 in Japan. Anti-E (1.2x, p<0.01 in South Korea and 1.3x, p<0.01 in Japan), anti-D (4.2x, p<0.01 in South Korea and 2.8x, p<0.01 in Japan) and anti-Jr^a (9.5x, p<0.01 in Japan) were detected more frequently in female patients than in male patients. The number of pregnant and non-pregnant female patients analyzed were 252 and 1,270 in South Korea, 1,007 and 4,710 in Japan, respectively. Anti-D was 8.0 and 1.7 times more frequently detected in pregnant than non-pregnant patients from South Korea and Japan, respectively (p<0.01 in both cases). Anti-Jr^a was 2.0 times more frequently detected in pregnant than non-pregnant patients in Japan (p<0.01). No Anti-Jr^a was detected in patients from South Korea. Anti-c+E was 2.9 times more frequently detected in pregnant than non-pregnant patients in Japan (p<0.01), but this difference was not observed in patients from South Korea. In all, 13 alloimmunized anti-D cases were detected in pregnant patients and 141 anti-D cases in pregnant patients who received anti-D immunoglobulin among 26 institutions in Japan. This data was not included in the analysis.

Conclusion: In this study, data obtained from a collaborative study conducted in South Korea and Japan on alloimmunity to erythrocyte antigens was analyzed. The frequencies of several Abs were different between both countries, and different from other reports. Anti-D and anti- Jr^a were more frequently detected in pregnant patients. These results could be important when considering the mechanism of maternal-infant allo-immunization as well as ethnic differences. The reason for the observed variation in the two countries will be further investigated by a prospective study and erythrocyte antigen analyses.

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