The Human Leukocyte Antigen (HLA) genes are those which are responsible for detecting foreign substances and triggering the immune system. Such HLA screening includes the detection of drug molecules, bacteria and viruses as well as the process of self recognition, such as the screening of tumor cells and autoimmunity. HLA variation is, of course, also the basis for organ transplant rejection. As a result, complex HLA genetic testing is now the standard of care for all of transplantation medicine, performed on @100,000 individuals per year worldwide and, as such, is the recognized gold standard for the field of personalized medicine.
A complex “HLA-like” genetic test is ideally suited to microarray technology, since microarrays can easily detect one thousand to one million local DNA changes in parallel. In spite of that apparently-ideal fit, there are only a couple of microarray tests used in HLA testing today; the reason being that the existing microarray technologies were developed as research tools, not as a platform for clinical or public health screening. Thus, in their current form, microarrays are too complex, too expensive, and require a sample size that is too big to be implemented, practically, as part of large scale genetic testing.� However, GMSbiotech has solved this issue with its high resolution low cost micro array platform.
Beyond organ transplantation and vaccine response, there is now very strong evidence that personal variation in the HLA genes is also directly related to personal variation in the risk of viral infection; the risk of inflammatory joint disease; and very importantly, the dose limiting inflammatory response to drugs, known as “drug rash” or in extreme cases, the life-threatening Stevens-Johnson Syndrome (SJS).
Table
I. The Current Role (late 2008) for High Resolution HLA-B Testing: For
AIDS
Risk, Acacabir Pharmacogenomics, Reactive Arthritis
& other HLA-based diseases.
HLA-B Allele | Clinical Indication correlated with Allele | Comments Relative to Clinical Utility of HLA-B screening | Ref. |
---|---|---|---|
B*07 |
Ebola.
Protective (with B*14). Non-Fatal response to Ebola |
B*07
+ B*14 are highly enriched in those who survive |
1). |
B*11 |
Chlamydia
trachomatis. Protective against blindness from Chlamydia trachomatis |
Predictive
of those who do not develop blindness |
2).
|
B*14 |
Ebola.
Protective, (along with B*07). Non-Fatal response to Ebola |
B*07
+ B*14 are highly enriched in those who survive |
1).
|
B*15 |
Ebola.
Sensitizes
(with B*67) a Fatal response to Ebola |
B*67
+ B*15 highly enriched in those who perish |
1).
|
B*1502 |
Adverse
Drug Response. Carbamazepine induced Stevens-Johnson in Chinese |
FDA:
All Chinese should be screened before Rx |
3).
|
B*1502 |
Adverse
Drug Response. Carbamazepineinduced Stevens-Johnson in Chinese |
Only
solid psychiatric marker for pharmacogenomics |
4).
|
B*17 |
Lukemia
in children. |
B*17
and A*33 may combine to predict male relapse |
5). |
B*27 |
Ankylosing
Spondylitis. (reactive arthritis). B*27 explains 50% of risk |
Severity
of reactive arthritis strongly correlated with B*27 |
6).
|
B*27 |
Ankylosing
Spondylitis (reactive arthritis). B*27 plus IL-1 explain 75% of risk |
Severity
of reactive arthritis strongly correlated with B*27 |
7).
|
B*27 |
Ankylosing
Spondylitis. (reactive arthritis). B*27 Correlates with increased
arthritic pain in Reactive arthritis after a triggering infection |
Severity
of reactive arthritis strongly correlated with B*27 |
8).
|
B*27 |
Reactive
Arthritis. B*27 associated with Enhanced Risk of severe Reactive
arthritis |
Clinical
B*27 Review in Nature |
9).
|
B*27 |
Chrone’s
Disease. HLA-B27 appears to convey a very high risk of developing axial
inflammation in Crohn's disease. |
B*27
not associated with absolute Chrone’s risk, but with subsequent
inflammation. |
10).
|
B*27 |
HIV-1.
All B*27 alleles Protective, HIV-1 Elite Controller |
Also
seems to correlate with early work on vaccines |
11).
|
B*27 |
HIV-1.
All B*27 alleles Protective, HIV-1 Elite Controller |
HIV-1
can mutate out of suppression faster in B*27,Relative to B*57 |
12).
|
B*3503 |
HIV-1.
B*3501 is protective for HIV progression, Other
B*35 alleles show rapid HIV progression |
As
for B*57, a subtle change in B*35 allele has significant effects |
13).
|
B*39 |
Diabetes.
Type I diabetes genetic risk explained by B*39 Plus HLA-DQB1 and
HLA-DRB1 |
High
profile whole genome scanning study in Nature |
14).
|
B*4402 |
Cervical
Cancer. Enhanced squamous cell cervical cancer RISK with one or more;
A*0201-Cw*0501 DRB1*0401-DQB1*0301 |
HLA
explains enhanced genetic risk for Cervical cancer. B*4402 is central
theme |
15).
|
B*51 |
Beh�et's
disease. Autoimmune disease of the vasculature |
B*51
is strongly correlated with severity |
16).
|
B*5401 |
Gastric
Cancer. Reduced risk of gastric cancer |
Mediated
via H.Pilori infection |
17).
|
B*57 |
HCV.Protective
effect |
All
B*57’s correlated with spontaneous recovery |
18).
|
B*5701 |
Adverse
Drug Response. Abacavir sensitivity |
Large
scale US. Screening trail confirms predictive power for ADR |
19).
|
B*5701 |
Adverse
Drug Response. Abacavir sensitivity |
Described
as “Gold standard” in 2009 for personalized medicine |
20).
|
B*5701 |
Adverse
Drug Response. Abacavir sensitivity |
NEJM
landmark paper. Large scale Australian Screening trail confirms high
predictive power for ADR |
21).
|
B*57 |
HIV-1.
Protective effect HIV-1, the Elite Controllers. HLA-B and
KIR3DL1/KIR3DS1 |
Clinical
Screening is now routine. The best characterized host protective effect
in modern infectious disease research |
22).
|
B*5701 |
HIV-1.
Protective Effect HIV-1 Elite Controller. Highest genetic correlation.
HLA-C may be a secondary player |
The
role of B*5701 in HIV risk upon infection is the gold standard in host
effects in infectious disease |
23).
|
B*5702 |
HIV-1.
Not Protective HIV-1 Elite
Controller |
B*5701
& B*5702 must be cleanly resolved at high resolution. For HIV
progression & Abacvir ADR |
24). |
B*5703 |
HIV-1.
Protective Effect HIV-1 Elite Controller |
Protective
Mechanism is different than for B*5701 |
25).
|
B*5801 |
Adverse
Drug Response. Allopurinol sensitivity in Chinese |
Highly
predictive of adverse response to allopurinol |
26a).
26b).
|
B*5801 |
HIV-1.Protective
Effect HIV-1 Elite Controller |
More
escape variants than for B*5701 |
27).
|
B*67 |
Ebola.
Sensitizes (with B*15) Fatal
response to Ebola in Uganda |
B*67
+ B*15 highly enriched in those who perish |
1).
|
B*67 |
Lukemia
children. Male |
|
28).
|
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