HLA types – the important stuff

Howdy guys

Today chromosome 6 is the featured puppy

HLA recall can make little sense and seem to bear little relation to clinical practice, though crops up with monotonous regularity in exam questions

Those setting the papers are aware you can’t know everything ever written. They have also been through it themselves. Most are medically qualified doctors. This is a good thing. This means that all those baffling letters and numbers and associated diseases have just got a whole lot easier to learn

The most clinically important we will look at. The ones with the strongest associations we will touch on. All the rest you can learn from your favourite set of lecture notes /weighty text book / temporary doorstop if you are so inclined – we will skip those and wander down to the beach / park for an ice cream / cold beer (delete as appropriate)

 

OK some basics..

HLA is human leucocyte antigen. This means that it is a little protein sitting on the cell surface, where it is seen by white cells. It is the body’s way of expressing itself (rather than nail polish or a fancy hat) – and as such its other name is the major histocompatability complex. It also presents antigen (bits of protein which can be seen by the immune system and dealt with by either ignoring them or mounting an immune response)

All along chromosome 6 (did I mention sex? – only in a New Zealand accent) are particularly bits (loci) which code slightly different proteins. Each of these has some variability between individuals and these are responsible for transplants being recognised as ‘non-self’ and being rejected

The HLA comes in two main flavours Class I (HLA-A, B, C, E, F and G) – note that D isn’t there

..and Class II (HLA-DP, DQ and DR) – here’s the ‘D’

 

Before you get too scared let me remind you that HLA-A, B and C are the important class I ones and that HLA-DR (like Dr) are the most mentioned for class II

 

HLA class I presents intrinsic antigen to cells that express CD8 (natural killer cells) 

(1×8 = 8 and the i of intrinsic looks like I)

HLA class II presents extrinsic antigen to cells that express CD4 (eg T helper cells)

(2×4 = 8 ..both the sums shown add up to 8 and II if demonstrated with your arms can make an x like X-factor which reminds you of extrinsic)

 

Lets recap. MHC = HLA. Class I and II. They have a role in presenting antigen and as such in self recognition. It follow that that play a role in auto-immunity. They also play a role in cancer. So they’re important

 

The commonest question example is HLA-B27  - this is quite well associated with ankylosing spondylitis (this is a progressive inflammatory condition mainly of the spine which becomes more bamboo like radiographically and when you become hunched over, you do have the dubious advantage of never having to step in dog poo again…. cos you’re always looking at the floor)

HLA-DR3 and 4 is associated with rheumatoid arthritis

(do note here that not all people with anklyosing spondylitis have HLA-B27 and not all people with rheumatoid have HLA-DR3, they are just more likely to – also note, dear reader that if you have HLA-B27 you are not guaranteed to get anklyosing spondylitis  and if you have HLA-DR3 you are not doomed to rheumatoid arthritis. They are associations. We said that earlier and I reiterate – just an association)

 

HLA allele	Diseases with increased risk	Relative risk (%)
HLA-B27	Ankylosing spondylitis	90-100
	Postgonococcal arthritis	14
	Acute anterior uveitis	15
HLA-DR3	Autoimmune hepatitis	14
	Primary Sjögren syndrome	10
	Diabetes mellitus type 1	5
HLA-DR4	Rheumatoid arthritis	4
	Diabetes mellitus type 1	6
HLA-DR3 and-DR4 combined	Diabetes mellitus type 1	15
HLA-B47	21-hydroxylase deficiency	15

 

 

 

I hear you cry ‘but if they are only associations what clinical use are they?’

Good question. Easy answer is not much. BUT – it seems that the more we discover about these the more important they seem and thus it would be reasonable to assume that they will be rather important in the future

Genetics is a rapidly evolving field (if you excuse that slight pun – or being English in the summer, a punnet, if you will) and having students aware of what is happening now to prepare them for the big wide medical world when they are released into the wild to fend for themselves on graduation, makes a lot of sense to those in medical education who try to put together the best medical course that they know how to

For those clever sausages of you note that HLA-B51 is associated with Behçet’s

Now coeliac disease, HLA-DQ2 and HLA-DQ8 are the two to remember

Test	sensitivity	specificity
HLA-DQ2	94%	73%
HLA-DQ8	12%	81%

 

Some of you will encounter Dw3 Dw1 and similar. This is where a cellular way of looking at the DR (Dr) locus was done. This had some use, but will probably be superseded by genetic techniques

 

Now if you’ve read this far, go and have a small lie down – you deserve it

 

All the best

 

Dr B