Anti-LuB aka LU2

Blood Group: Lutheran

Common: Extremely rare. 0.122% of people are at risk for developing anti-LuB (2)

Transfusion Reaction: Mild to moderate. <0.2% of blood is compatible (18).

Causes HDN: Yes, Mild - “The presence of the Lutheran glycoprotein on placental tissues may result in absorption of maternal antibodies to Lutheran antigens.”17
Critical Titer: 1:16

Information:


Around 1957 the first two examples of anti-Lub were described. It had long been predicted that anti-Lub would exist, but there had never been a reported case before (2). The original Lutheran antibody, anti-Lua was found in 1946. By 1968 at least 11 cases of anti-Lub had been described in the literature 11.


Lutheran antigens belong to a blood group where two main alleles, Lua and Lub make the current phenotypes Lu(a-b+) 93.07%, Lu (a+b-) 0.122%, and Lu (a+b+) 6.81% (2). A null phenotype Lu(a-b-) also exists which lacks all Lu antigens, including Lua and Lub (3). It is unknown if it is possible to have antibodies to both Lua and Lub or if a an additional Lutheran antibody that will react with both Lua and Lub will be discovered like in the Kidd blood group (4).

Note: anti-Lu 3, 4, 5, 6, 8, and 11 have been found (17). Anti-Lu11 does not react with cells that are Lu(a-b-) (16).


There are a couple of articles that talk about freezing blood from the pregnant woman herself, compatible siblings or unrelated individuals' red blood cells. This was used for anti-Lutheran b, anti-PP1Pk, and a rare genotype of anti-c. (1, 17)


Anti-Lub can cause mild Hemolytic Disease of the Newborn (12). One article suggests that the Lutheran antigens are only weakly expressed at birth and that may be why there are no severe cases of HDN from anti-Lub in the literature (13). A second article says that Lub antigen is weaker in fetuses than adults, and was not detected in a fetus of 9 weeks, despite having inherited Lub from both parents (15). Additional articles confirm weak expression of the Lub antigen at 8 and 10 months of age.  Lutheran antigens are found on the surface of the cells that become blood cells, so anti-Lutheran may destroy the progenitor cells before they even turn into red blood cells. Because the precursor cells do not have hemoglobin, less bilirubin is released, which may mean that jaundice can be less common in infants, but the underlying anemia may still be present (3). This is similar to anti-Kell and anti-M antibodies. Cord blood grouping on infants was found to give a “appreciable, highly significant, occurrence of false negatives in Lua grouping” (14). This suggests that cord blood typing may not be accurate for the Lutheran antigens.


In summary, not much is known about anti-Lub or how exactly it works in relation to hemolytic disease of the newborn and fetus. There is a lot of theory, but little is known for sure except that it has not caused a severe case of HDN to date, but infants have required phototherapy from it. No cases of intrauterine transfusion, hydrops, or death from anti-Lub have been found in the literature, however this is a clinically significant antibody capable of causing disease and should be monitored.



Articles:

1- https://obgyn.onlinelibrary.wiley.com/doi/abs/10.3109/00016348209156560

2 - http://www.bloodjournal.org/content/bloodjournal/12/11/998.full.pdf?sso-checked=true

3 - http://www.jbc.org/content/273/27/16686.full

4 - https://www.ncbi.nlm.nih.gov/books/NBK2272/

5 - https://www.nature.com/articles/178855b0

6 - https://www.ncbi.nlm.nih.gov/pubmed/17725551

7 - https://www.ncbi.nlm.nih.gov/pubmed/17725727

8 - https://www.ncbi.nlm.nih.gov/pubmed/18366461

9 - https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1423-0410.1960.tb04039.x

10 - https://onlinelibrary.wiley.com/doi/pdf/10.1002/9780470987018.ch6

11 - https://watermark.silverchair.com/ajcpath49-0652.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAb0wggG5BgkqhkiG9w0BBwagggGqMIIBpgIBADCCAZ8GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMCTxnheKOobbQi3VFAgEQgIIBcE2ZDVBcPPwmtJTQnXM4ii58EmibYyMAuKoO7WdA6HcUrBTZiQOdr7msD-

zHD2i5jPRMWUSIsfDyWRtdme4eE1Yyv3zyIVhTaAVgdQgJ4ANR-qCv-QxkEgG-abIuVO_gO8lHwwU45LYLJVrQGkDm8CgpjKOfBoBhrUpdPAwxetHXt0WzxzjTDHUNz2G4GoZ1Dfj6DUmvP-NEL6GWFJ5SavrtIkFOopWnJuzfg5yrjEYDGdYSJebC0gCAJ-qQOkdiBiGGnIrv5Z5UVgAF9X1GrsuteYeMslcLbmBk7-DtsWUeq9sOR4GryNpla6siKFoVwB_0C0z6ryKQKfBiexHimqSwN2BmzCRvPQMBj9xXF0ctd657MeU6TjBcFrwbOub0-z5Qz2AMng9V8Gpv6QfjkgTd2YpItcb8BbM98l4tfZC5LVINgdZeZw5gRA_GQ9zEKkc_dyqgPylJFcoVeQdOuGTWHGdA6FLNXEU5_e83pTPr

12 - https://onlinelibrary.wiley.com/doi/full/10.1111/j.1537-2995.1966.tb04764.x?scrollTo=references

13 - https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1537-2995.1967.tb05509.x

14 - https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1423-0410.1968.tb01698.x

15 - https://www.researchgate.net/publication/17380824_Fetal_Development_of_Red_Cell_Antigens_K_k_Lua_Lub_Fya_Fyb_Vel_and_Xga

16 - https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1423-0410.1974.tb02388.x

17 - https://books.google.com/books?id=XVTc49cTw3MC&pg=PA283&lpg=PA283&dq=anti-+Lu+11&source=bl&ots=q3DufUxzaE&sig=5YbaJsew5HuHDeFt9_liraNF-x0&hl=en&sa=X&ved=0ahUKEwiF4d-Hsp_aAhWG6lMKHaFmAAYQ6AEIVjAG#v=onepage&q=anti-%20Lu%2011&f=false

18 - http://www.pathology.leedsth.nhs.uk/pathology/ClinicalInfo/AntenatalTesting/AntibodiesinPregnancy.aspx

19 - https://www.karger.com/Article/Abstract/462163
20 - http://www.redcross.org/images/MEDIA_CustomProductCatalog/m4440096_25_4_09.pdf