Monday 26 September 2016

Blood groups I

This year, as previous years, my first Human Physiology class featured the Induction Quiz, which exposes the students (anonymously!, this is not an exercise in class shaming) to their own ignorance about how the human body - including their own - is organised and how it functions.  Just as well we don't have to think our digestive system or pancreas into working.  As every year, everyone knew their zodiacal birth-sign, but less than half knew their blood group. Those who did know clapped down O+, or A negative as the case may be and went on to the next question. But precious few of those in the know could have parsed out what O+ meant and how it differed from O-. Chances are you don't know either, so I'll explain. As a teaser, let me say here that this information is the foundation/trailer for one of the most shocking and expensive medical negligence class-action suits in Irish history.

The first thing to note is that the O/B/A part is completely different from and independent of the +/-, but they both refer to immunological variability among the red blood cells.  All your red blood cells are the same of course, but they are very likely to be different from mine, and less likely to be different from those of your sister [it's the genetics!]. Why immunological? Because the immune system is tasked to recognise foreign entities in blood and tissues and knock 'em on the head before they start a riot. You are made up of about 100 trillion cells, all with 46 chromosomes and 'human', but you also tote around about 200 trillion cells of maybe 10,000 different species of bacteria. We can't function at all at all unless both of these cohorts are present: they are recognised as 'self' or tolerated as 'commensal'. The cells of the immune system, mostly various types of white blood cell, patrol the body looking for things, mainly proteins, that are non-self. These include nematode worms, malarial parasites, Vibrio cholerae, and HIV. But also, amazingly and effectively, they recognise the rogue males of the body - cancer cells - and almost always nobble them before the incipient tumor is detectable by the most sensitive equipment in the Dana Farber Cancer Institute. Go immune system!

The way white cells approach the rest of the 100 trillion is to get up close and personal and frisk them for the proteins that are sticking out of the cell membrane. If these proteins are within the normal range, which the immune cells have been practicing on since birth, then they are left alone; if they feel a bit funny then that cell is immediately dismembered and the parts recycled. The sticky-out proteins are called antigens because they generate a response from the antibodies of the immune system.

Now here's a funny thing: there are two antigens that stick out of red blood cells RBCs which we call A and B. You, personally, may possess either, neither or both of these things and nobody really knew or cared about them until a bit more than 100 years ago, when doctors started to do blood-transfusions. Sometimes this would go fine but many times it would make the sick person very much less well because his immune system took agin the foreign influx. There seemed to be a reliable and reproducible pattern as to whose blood was compatible. As with kidney transplants today, siblings were more likely to have compatible blood but not always. And some people seems to be good donors regardless of the recipient. Since Jan Janssky worked it all out and Karl Landsteiner got the Nobel prize [Prev], we've called this system of antigens the ABO blood groups. A has one antigen; B has the other; AB have both; and O have neither. The frequency of these blood groups varies across the world [see above for the B group which is commonest in a belt across central Asia and completely absent among Native South Americans. In all populations, the gene frequency of the O variant is always above 50%, so is most common. We have theories but no certainty about why there is this pattern of variation. If Hercule Poirot addresses a multi-racial roomful of people and says that one person present matches the blood group B which was found on the bloody knife left in the bread-bin - put money on it being the lady from Pakistan.

The weird thing is that if you have A-antigens on your RBCs your immune system is hopped up with antibodies against B and vice versa. That's what caused the rapid downhill in certain transfusions: delivery of 500ml of fresh A blood elicited a firmly destructive immune response from people with blood group B or O; and the debris clogged the capillaries. AB people with both antigens A and B have neither antibody present [it would be a disaster if they had, if you think about it] , so they can take blood from anybody. Whereas O people, having both anti-A and anti-B circulating, need to be a lot more picky. If you can't get your head around it, the diagram [R] might help.

Nobody has given me a convincing explanation of what these little proteins do in the normal body; or the even greater mystery about why we are all charged up to deal adversely with certain blood-transfusions. Twenty years, a charlatan called Peter D'Adamo, Grand Naturopathic Wizard of Woowah College, published a book called Eat Right For Your Type which topped out the NYT best-sellers list for several week. The credulous clearly bought into the idea that your diet might be incompatible with the antigens on your RBCs. One of the arguments against this is that the human diet is very different from that of other primates, but they show the same polymorphism in the ABO system. I've crossed it out because I'm cross about arrant nonsense which has a) made a fortune for D'Adamo and b) been comprehensively disproved by large scientific studies,

But here's a further peculiarity about ABO blood groups, which might give us clues about why we're all different, Group O is more likely to develop squamous cell and basal cell carcinoma but less likely to get pancreatic cancer. So it's like the CCR5 mutation which resistance to HIV but makes the carriers more susceptible to West Nile Virus. There is some evidence that gastric cancer is more prevalent in Group A. These conditions are comparatively rare and were much rarer when we all died young of hyena, spear or pneumonia. There is a hint of evidence that Group O are more susceptible to cholera, which was a serious scythesman among any static conglomeration of people where the water supply could get contaminated with the runs.

1 comment:

  1. This has to be one of the best descriptions of immunology and the ABO blood system I've read in years