Thank you so much, Lesley, for bringing this to my attention.
The original post can be seen here:
Universal “panda blood” developed by engineering cell surfaces
“Panda blood” refers to the Rh-negative blood type in China, which, as the phrase suggests, is “as rare as pandas”. It is estimated that about 3 out of 1000 Chinese people have the Rh-negative blood type.
Due to its extreme rarity, Rh-negative blood is constantly in short supply. Whether this life-saving blood can be available in a timely manner plays a critical role in the life of the patient with the Rh-negative blood type.
To address this challenge, the research team led by TANG Ruikang, a professor from the Department of Chemistry, and WANG Ben, an associate professor from the Second Affiliated Hospital of the Zhejiang University School of Medicine, successfully engineered universal “panda blood.” They developed an alternative approach to sheltering the epitopes on RhD-positive RBCs using a surface-anchored framework and achieved the fabrication and transfusion of this universal “panda blood”. These findings are published in the March 20 issue of Science Advances.
The pioneering studies of Karl Landsteiner in the 19th century provided a solid foundation for our current understanding of blood types. The major human alloantigen system involves the ABO, Rhesus (Rh), MNS, Lutheran, and Kell blood groups. The Rh blood group system is a clinically notable human blood group polymorphism in alloimmunization and includes more than 50 different serologic specificities, which makes this system particularly paramount and challenging for biomedical scientists and clinicians. Within the Rh blood group, the D antigen is the most immunogenic and clinically vital epitope. As a rare blood type, there is a dire deficiency in the bank of RhD-negative blood for transfusion, especially in emergencies. Exposure of RhD-negative individuals to RhD-positive blood may cause serious immune responses, including hemolysis, which is life threatening.
Is there any “once-and-for-all” solution to this formidable challenge? The research team led by TANG Ruikang and WANG Ben developed a novel technique to engineer cell surfaces for the production of RhD-negative RBCs using a rationally designed three-dimensional (3D) crosslinking framework of polysialic acid (PSA)–tyramine hydrogel, which has a flexible texture to ensure cell membrane stability. This technique for the anchored framework can balance the modified RBC membrane fluidity and RhD antigen shielding and achieve the successful transfusion of the engineered RhD-positive RBCs to RhD-negative recipients without immunogenicity.
This universal “panda blood” was already tested in a mouse model and these results indicated that surface engineering leads to negligible complement activation and cytokine response and presents good biocompatibility. Furthermore, the systematic biosafety of engineered RBCs was investigated in a rabbit model, which indicated that surface modifications can not only bypass anti-RhD immunity but also promote favorable biocompatibility. This study, therefore, holds great promises for clinical translation.
This study demonstrates a biocompatible membrane-anchoring self-assembly method for cell surface engineering. This approach may promote immunological applications by sheltering antigens of tissues and cells at the single-cell level. Researchers believe that the application of cell surface engineering will provide an alternative to preventing rejection reactions with control over cellular functions through material transformation.
In addition to our follow-up research into universal red cells, the compatibility issue in platelet transfusion is more troublesome, WANG Ben said. “In the not-too-distant future, there may be more chemical-biological ways to convert cells and endow them with more functions, opening up the possibility of their applications in medicine,” WANG Ben added.
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Yes…I do read this and more. Our best hope for understanding Rh Neg is to look at and compare the scientific work being done in all countries. In lighter mode, I doubt that the Chinese give any credence to the crazier ideas running around in the US on Rh Neg and other topics ! In California, many sane people are looking at the fusion of traditional Asian and Western medecine.
the process looks helpful for what it was designed to do. since red blood cells (RBCs) tend to live about 115-120 days for healthy individuals, they will be removed by the liver and such eventually. i suspect these altered RBCs will have some other issues, but if they help someone survive a transfusion for an Rh neg blood type in a place where the required blood type is rare – then, that’s a good thing by itself.
i’m wondering if anyone has seen and/or read this maybe 98 page book…either in reality or as it is here as a completely accessible online book:
Blood Groups and Red Cell Antigens – by Laura Dean, MD
Bethesda (MD): National Center for Biotechnology Information (US); 2005.
“Blood Groups and Red Cell Antigens is a guide to the differences in our blood types that complicate blood transfusions and pregnancy. It accompanies the dbRBC, a new NCBI resource that contains clinical and DNA data about human red blood cells.”
https://www.ncbi.nlm.nih.gov/books/NBK2261/
https://www.ncbi.nlm.nih.gov/books/NBK2261/pdf/Bookshelf_NBK2261.pdf
some quotes from sections of this book:
Chapter 5 The ABO blood group
Frequency of ABO blood group antigens
A: 43% Caucasians, 27% Blacks, 28% Asians
B: 9% Caucasians, 20% Blacks, 27% Asians
A1: 34% Caucasians, 19% Blacks, 27% Asians
Note: Does not include AB blood groups (1).
Frequency of ABO phenotypes
Blood group O is the most common phenotype in most populations.
Caucasians: group O, 44%; A1, 33%; A2, 10%; B, 9%; A1B, 3%; A2B, 1%
Blacks: group O, 49%; A1, 19%; A2, 8%; B, 20%; A1B, 3%; A2B, 1%
Asians: group O, 43%; A1, 27%; A2, rare; B, 25%; A1B, 5%; A2B, rare
Note: Blood group A is divided into two main phenotypes, A1 and A2 (1).
Chapter 7 The Rh blood group
“The significance of the Rh blood group is related to the fact that the Rh antigens are highly immunogenic. In the case of the D antigen, individuals who do not produce the D antigen will produce anti-D if they encounter the D antigen on transfused RBCs (causing a hemolytic transfusion reaction, HTR) or on fetal RBCs (causing HDN). For this reason, the Rh status is routinely determined in blood donors, transfusion recipients, and in mothers-to-be.
Despite the importance of the Rh antigens in blood transfusion and HDN, we can only speculate about the physiological function of the proteins, which may involve transporting ammonium across the RBC membrane and maintaining the integrity of the RBC membrane.”
Frequency of Rh antigens
D: 85% Caucasians, 92% Blacks, 99% Asians
C: 68% Caucasians, 27% Blacks, 93% Asians
E: 29% Caucasians, 22% Blacks, 39% Asians
c: 80% Caucasians, 96% Blacks, 47% Asians
e: 98% Caucasians, 98% Blacks, 96% Asians (1)
Frequency of Rh phenotypes
Rh haplotype DCe: most common in Caucasians (42%), Native Americans (44%), and Asians (70%)
Rh haplotype Dce: most common in Blacks (44%)
Rh D-negative phenotype: most common in Caucasians (15%), less common in Blacks (8%), and rare in Asians (1%) (1)
————
—- so, roughly 15% of whites are Rh(D) negative, 8% for blacks & 1% for asians —-
those were the #’s she used/gave in this book in 2005. if we assume these #s are still reasonably accurate, then i/we can use them for CVD19 data analysis now and for other things and studies. noting when relevant, if a population area or group is noticeably different from these global averages.
“It was wrongly thought that the agglutinating antibodies produced in the mother’s serum in response to her husbands RBCs were the same specificity as antibodies produced in various animals’ serum in response to RBCs from the Rhesus monkey. In error, the paternal antigen was named the Rhesus factor. By the time it was discovered that the mother’s antibodies were produced against a different antigen, the rhesus blood group terminology was being widely used. Therefore, instead of changing the name, it was abbreviated to the Rh blood group.”
—- the following section is complete quote of that section from the book: —-
Basic biochemistry
Common Rh phenotypes
“” The most common Rh haplotype in Caucasians, Asians, and Native Americans is DCe. In Blacks, the Dce haplotype is slightly more common (1).
In Caucasians, the Rh D-negative phenotype results from a deletion of the RHD gene. About 15% of Caucasians are Rh D-negative.
In Africans, there are three molecular backgrounds that give rise to the Rh D-phenotype which is found in 8% of the population. One is the RHD gene deletion that is common in Caucasians. The other two mechanisms are inheriting a RHD pseudogene (contains a duplication of nucleotides that introduces a premature stop codon) or inheriting a RHD hybrid gene (contains nucleotide sequences from the RHCE gene, produces no D antigen and abnormal C antigen) (3)
Uncommon Rh phenotypes
The D antigen contains over 30 epitopes. Variations of the D phenotype arise when these epitopes are only weakly expressed (“weak D phenotype”) or when some are missing (“partial D phenotype”).
Weak D: all D antigen epitopes are present but are underexpressed
“Weak D” is a Rh phenotype found in less than 1% of Caucasians and is only slightly more common in African Americans (2). It is typically caused by a single amino acid switch in the transmembrane region of the RhD protein. This disrupts how the RhD protein is inserted into the RBC membrane, reducing the level of expression of RhD. In most cases, adequate levels of D antigen are present and because there has been no change in D epitopes, the formation of anti-D is prevented. Therefore, individuals with the weak D phenotype can receive Rh D-positive blood.
Partial D: some D antigen epitopes are missing
In contrast, people who have been identified as having the “partial D” phenotype should not receive Rh D-positive blood but in practice, people with partial D are difficult to identify. This phenotype is usually caused by the creation of a hybrid RhD and RhCE protein. The hybrid protein is similar enough to RhD to be correctly inserted in the RBC membrane, but it lacks several epitopes found on the complete RhD protein. If a person with the partial D phenotype encounters the complete D antigen on transfused RBCs, they may form anti-D and suffer from a transfusion reaction. “”
——–
Function of Rh proteins
“The Rh antigens are thought to play a role in maintaining the integrity of the RBC membrane—RBCs which lack Rh antigens have an abnormal shape.
Individuals with the rare Rhnull phenotype caused by the deletion of RHAG have RBCs that do not express any of the Rh antigens because they cannot be targeted to the RBC membrane. The absence of the Rh complex alters the RBC shape, increases its osmotic fragility, and shortens its lifespan, resulting in a hemolytic anemia that is usually mild in nature. These patients are at risk of adverse transfusion reactions because they may produce antibodies against several of the Rh antigens”
Clinical significance of Rh antibodies
“Whereas most blood types are determined by red cell antigens that differ by one or two amino acids, the Rh blood group contains the D antigen which differs from the C/c and E/e antigens by 35 amino acids. This large difference in amino acids is the reason why the Rh antigens are potent at stimulating an immune response (4).
The majority of antibodies formed against the Rh antigens are of the IgG type. They are capable of causing significant HTR and HDN. Rh antibodies rarely, if ever, bind complement, and therefore RBC destruction is mediated almost exclusively via macrophages in the spleen (extravascular hemolysis).”
Molecular information
Gene
“The Rh locus is located on the long arm of chromosome 1 (on 1p36-p34). It contains the RHD and RHCE genes, which lie in tandem. The RHD and RHCE genes are structural homologs and result from a duplication of a common gene ancestor.
RHD and RHCE each contain 10 exons and span a ~75-kb DNA sequence. The RHD gene is flanked by two 9-kb, highly homologous sequences called “Rhesus boxes” (14, 15). It is thought that unequal homologous recombination confined to the Rhesus boxes is a common cause of the deletion of the RHD gene, which is found in up to 40% of the population.”
Protein
“The RHD and RHCE genes each encode a transmembrane protein over 400 residues in length that traverses the RBC membrane 12 times. The RhD protein only differs from the common form of the RhCE protein by about 35 amino acids.”
Ken:
I like your train of thought and will look at the book. The very pertinent quotations that you give do correspond to the essential Rh facts in other sources…and give us all good clues as to what to look for.
I am trying to do a literature search on Rh Neg issues and findings. There is a lot out there !
Mike et al:
A further citation on Rh Neg in China is this
https://pubmed.ncbi.nlm.nih.gov/17029213/
Once in that system, there are several other good citations and references on Rh neg in China and its distribution within and among minority groups in China.
This a further evidence trail that confirms “that there is something there”. Such distributions are clearly not random and must have some form of explanation.
A similar non-random pattern emerges for India.
Cheers
Richard
Just a quick FYI:
WP/Akismet have been going crazy this year when it comes to placing comments into the spam folder that don’t belong there. Now that some of you have been approved to comment without moderation, certain comments still appear to require moderation on my part. Usually, those comments have certain terms such as the “v-word” (Wack Seen) in them. Even when the comments are not critical, the word alone appears to pull the trigger. Other alternative medicine related subjects and terms seem to do so as well. I just wanted to make sure that all of you understand I haven’t changed anything in the settings and the approval mode is what I have changed it to a couple of days ago.
for my long comment above that required you to approve it, i was logged in and was working on that post for probably an hour or more while i was reading & researching. i had copied and saved my comment and decided to refresh this page to see if an other comments had been made, and was surprised to see my comment had been submitted and it said it was waiting for approval. i went inside WordPress and tried to approve that comment/my long post from above, but was not able to do it. anyway, that’s my side of things. no problems really…seems better this way. i just log-in if i have something to say/post and see what happens. saves me having to type in a posting name and my email address like i had to in days past…and once again, i looks like i can create an actual new topic thread like you. we’ll see. i’ll try the new topic thing when i’m certain i’ve got something very original to present. new ideas/insights seem to happen often to me…so, maybe it’s just a question/a matter of me actually following through and doing it.