Allo-Immunity to Erythrocytes in Relation to Blood Transfusion and Pregnancy: Cooperative Study of Allo-Immunity to Antigen Diversity in Asian Populations.
Authors: Takeshita Akihiro , Watanabe Hiroko , Kim Dae Won , Han Kyou Sup , Kwon So Yong , Suh Jang Soo , Natalie Chan Pui Ha , Nadarajan Veera Sekaran , Marican Nuranissa Bte Yacob , Permpikul Parichart , Uchikawa Makoto , Kino Shuichi , Ohto Hitoshi 
Published: October 2019

Abstract
Abstract 3144
Poster Board III-81

Purpose
Allo-immunization to erythrocytes is an important issue with regard to blood transfusions, albeit perhaps less prominent than other possible adverse effects. Several studies including pregnant and transfused cases have been conducted in US and European counties. However, a sufficient international or interracial comparative study has not been performed yet. Asian populations contain a wide variety of genetics and circumstances. They may differ in immune responses to allo-antigens that are common among American and European populations. Because no confirmed nor detail information exists for many Asian populations, collaborative international study concerning these issues will improve blood transfusions and transplantations not only in Asia but also the world. (Method) Forty-eight institutes, including those in Japan (29), Korea (15), Hong Kong (1), Singapore (1), Malaysia (1) and Thailand (1), participated in this first cooperative study of Asian population examining allo-immunity to erythrocytes. The total number of independent cases included more than 866,000 patients. Ab screening methods adopted in these institutes included gel columns, beads columns, traditional tubes or some combination of these three. If a case was tested multiple times, we counted it as one case. Multiple antibodies detected during the study in one patient were separately analyzed. Patients with unconfirmed histories were excluded from the study. We analyzed and compared the frequencies of irregular antibodies (Abs) to erythrocyte antigens between patients of different gender, patients pregnant or not, and patients with and without previous blood transfusion.

Results
Abs were determined in 8,880 patients (male /female: 3,528 /5,482), including 1801 /2418 from Japan, 946 /1477 from Korea, 287 /688 from Malaysia, 214 /408 from Thailand, 237 /375 from Hong Kong, and 11 /15 from Singapore. Of note, anti-D Ab was more frequently detected in females (p<0.01), but varies among countries as follows; 0.6 /2.4 (male /female, %) in Japan, 1.7 /8.1 in Korea, and 8.0 /19.6 in Malaysia. It significantly increased in pregnant patients (4.8% in Japan, 35.9% in Korea, 34.0% in Malaysia), but did not increase in patients that had received blood transfusion. Other Abs including complex ones did not significantly increase in pregnant patients. Anti-D Ab was rare in other Asian counties. Anti-E Ab was 1.4 times more frequently detected in patients that had received blood transfusion. [Japan (2.4x), Thailand (3.1x) Hong Kong (1.3x) and Singapore (1.3x)]. Anti-Jka and -C Abs increased in patients that had received blood transfusion. Anti-Dia Ab increased 1.6 times more in Japan, but did not in Korea (0.5x). Anti-c+E complex Abs, increased in patients that had received blood transfusion in many Asian counties. However, other complex Abs such as Anti-Lea+Leb Abs did not.

Conclusion
Although there have been several previous reports on allo-immunity in pregnant and transfused cases, this is the first international collaborative study in allo-immunity to erythrocyte antigens in relation to gender, pregnancy and blood transfusion status in Asia. Anti-D Ab was frequently detected in pregnant female patients. Anti-E, -Jka and -C Abs were frequently detected in patients that had received blood transfusion. However, the frequency varies among Asian countries. These data will contribute to the international body of knowledge concerning allo-immunity, allowing for advancements in successful blood transfusion in Asia and the world. The number of cases might be small in the light of total Asian populations, therefore, we should continue and spread the study.

Disclosures
No relevant conflicts of interest to declare.