Human leukocyte antigen test





Definition

The human leukocyte antigen (HLA) test, also known as HLA typing or tissue typing, identifies antigens on the white blood cells (WBCs) that determine tissue compatibility for organ transplantation (that is, histocompatibility testing). There are six loci on chromosome 6, where the genes that produce HLA antigens are inherited: HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ, and HLA-DP.

Unlike most blood group antigens, which are inherited as products of two alleles (types of gene that occupy the same site on a chromosome), many different alleles can be inherited at each of the HLA loci. These are defined by antibodies (antisera) that recognize specific HLA antigens, or by DNA probes that recognize the HLA allele. Using specific antibodies, 26 HLA-A alleles, 59 HLA-B alleles, 10 HLA-C alleles, 26 HLA-D alleles, 22 HLA-DR alleles, nine HLA-DQ alleles, and six HLA-DP alleles can be recognized. This high degree of genetic variability (polymorphism) makes finding compatible organs more difficult than finding compatible blood for transfusion .


Purpose

HLA typing, along with ABO (blood type) grouping, is used to provide evidence of tissue compatibility. The HLA antigens expressed on the surface of the lymphocytes of the recipient are matched against those from various donors. Human leukocyte antigen typing is performed for kidney, bone marrow, liver, pancreas, and heart transplants. The probability that a transplant will be successful increases with the number of identical HLA antigens.

Graft rejection occurs when the immune cells (T-lymphocytes) of the recipient recognize specific HLA antigens on the donor's organ as foreign. The T-lymphocytes initiate a cellular immune response that result in graft rejection. Alternatively, T-lymphocytes present in the grafted tissue may recognize the host tissues as foreign and produce a cell-mediated immune response against the recipient. This is called graft versus host disease (GVHD), and it can lead to life-threatening systemic damage in the recipient. Human leukocyte antigen testing is performed to reduce the probability of both rejection and GVHD.

Typing is also used along with blood typing and DNA tests to determine the parentage (that is, for paternity testing). The HLA antigens of the mother, child, and alleged father can be compared. When an HLA antigen of the child cannot be attributed to the mother or the alleged father, then the latter is excluded as the father of the child.

A third use of HLA testing called linkage analysis is based on the region where the HLA loci are positioned, the major histocompatibility complex (MHC), which contains many other genes located very close to the HLA loci. The incidence of crossing-over between HLA genes during fertilization of the egg by sperm is generally less than 1%. Consequently, the HLA antigens from all six loci are inherited together and segregate with many other genes located within the same region of chromosome 6. Many of the MHC-region genes are involved in immunological processes. As a result, alleles that are known to increase the chance of developing various autoimmune diseases have remained associated with specific HLA alleles. For example, 2% of people who have the HLAB27 allele develop an arthritic condition of the vertebrae called ankylosing spondylitis. However, approximately nine out of ten white persons who have ankylosing spondylitis are positive for HLA-B27. Because of this association, the disease and this HLA type are linked. Thus, a person with ankylosing spondylitis who is also HLA-B27 positive would have family with a much higher likelihood of developing ankylosing spondylitis than those who are not. Some notable autoimmune diseases that have a strong association with HLA antigens include Hashimoto's thyroiditis (an autoimmune disorder involving underproduction by the thyroid gland) associated with HLA-DR5; Graves' disease (an autoimmune disorder associated with overproduction by the thyroid gland), associated with HLA-B8 and Dw3; and hereditary hemochromatosis (excess iron stores), associated with HLA-A3, B7, and B14.


Precautions

HLA testing is performed using WBCs. If possible, this test should be postponed if the patient has recently undergone a transfusion, because any WBCs from the transfusion may interfere with the tissue typing of the patient's lymphocytes.


Description

The HLA gene products can be grouped into three classes. Class I consists of the products of the genes located on the HLA-A, HLA-B, and HLA-C loci. These HLA antigens are found on all nucleated cells. Class II molecules consist of antigens inherited as genes from the HLA-DR, HLA-DQ, and HLA-DP loci. These HLA antigens are normally found only on B-lymphocytes, macrophages, monocytes, dendritic cells, endothelial cells, and activated T-lymphocytes. Class III molecules are not evaluated in histocompatibility testing.

Because the HLA loci are closely linked, the HLA antigens are inherited as a group of six antigens is called a haplotype. The probability of siblings having identical haplotypes is one in four. Therefore, siblings provide the opportunity for the best matches. They can donate bone marrow, a kidney, and a section of their livers, but they cannot donate other solid organs. Approximately 85% of transplants are organs from cadavers, and because the HLA antigens are so highly polymorphic, the chance of identical haplotypes decreases quickly.

Histocompatibility testing consists of three tests, HLA antigen typing (tissue typing), screening of the recipient for anti-HLA antibodies (antibody screen), and the lymphocyte crossmatch (compatibility test). HLA antigen typing may be performed by serological or DNA methods.

A laboratory will perform HLA typing by either the serological (blood fluid) or DNA method. In either case, HLA typing of HLA-A, HLA-B, HLA-DR, and HLADQ antigens is performed for solid organ transplants. HLA typing of HLA-C antigens is also included when tissue typing is performed for bone marrow transplants.

The antibody screen is performed in order to detect antibodies in the recipient's serum that react with HLA antigens. The most commonly used method of HLA antibody screening is the microcytotoxicity test. If an antibody against an HLA antigen is present, it will bind to the cells. The higher the number of different HLA antibodies, the lower the probability of finding a compatible match.

The third component of a histocompatibility study is the crossmatch test. In this test peripheral blood lymphocytes from the donor are separated into B and T lymphocyte populations. In the crossmatch, serum from the recipient is mixed with T-cells or B-cells from the donor. A positive finding indicates the presence of preformed antibodies in the recipient that are reactive against the donor tissues. An incompatible T-cell crossmatch contraindicates transplantation of a tissue from the T-cell donor.


Preparation

The HLA test requires a blood sample. There is no need for the patient to fast before the test.


Aftercare

The patient may feel discomfort when blood is drawn from a vein. Bruising may occur at the puncture site, or the person may feel dizzy or faint. Pressure should be applied to the puncture site until the bleeding stops to reduce bruising. Warm packs can also be placed over the puncture site to relieve discomfort.


Risks

Risks for this test are minimal, but may include slight bleeding from the puncture site, fainting or feeling lightheaded after having blood taken, or hematoma (blood accumulating under the puncture site).

Normal results

HLA typing either by serologic (blood fluid) or DNA methods is reported as the phenotype for each HLA loci tested. The antibody screen test is reported as the percentage of panel reactive antibodies (PRA). The percent PRA is the number of wells reactive with the patient's serum expressed in percent. The crossmatch is reported as compatible or incompatible.

Tissue typing results for both donors and recipients and antibody screen results for recipients are submitted to the United Network for Organ Sharing (UNOS) database. The database searches all regional donors that are ABO-compatible for an HLA-identical match. If none is found, the database searches the national database for ABO compatible donors and scores the match. A point system is used based upon several parameters, including the number of matching HLA loci, the length of time the recipient has been waiting, the recipient's age, and the PRA score.

Resources

BOOKS

American Association of Blood Banks. Technical Manual. 13th ed., Bethesda, MD: American Association of Blood Banks, 1999.

Beutler, E., et al., eds. William's Hematology, 6th ed. New York: McGraw-Hill, Inc. 2001.

Henry, J. B. Clinical Diagnosis and Management by Laboratory Methods, 20th ed. New York: W. B. Saunders Company, 2001.


OTHER

National Institutes of Health. [cited April 5, 2003] http://www.nlm.nih.gov/medlineplus/encyclopedia.html .


Mark A. Best

User Contributions:

Wafa Alnakhi
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Feb 15, 2006 @ 1:01 am
The article is very useful and I would like to know more and in details about HLA..
Thank you
Rohit
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Feb 21, 2006 @ 6:06 am
This artical gives me really good idea of HLA due to which some questions have arisen in me,
That is-
>during organ transplantation there should be HLA typing and blood group typing done, only if it matches the organ can be donated, then while blood transfusion there is no HLA typing done. Why is it so? basically blood contain both white and red blood cells and many other cells ,will not HLA present on the WBC's give rise to GVHD?
Please clear my doubt,
It will be very helpful for me,
Thanking You
Cathy
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May 23, 2006 @ 1:13 pm
When you get a blood transfusion, you only get red blood cells. We haven't done whole blood transfusion in many, many years. We take a donated unit, spin it down, and it is separated into three layers: Bottom is Red Blood Cells, thin layer is WBCs and platelets, and top liquid is plasma. The plasma is frozen, and platelets can be harvested from the thin layer, so nothing goes to waste.

That said, it is possible than when they separate the two, they don't squeeze off all of the WBC layer. You can ask for Leuko-poor packed RBCs. They have a filter that goes between you and the unit, and "strains" out the much bigger white cells.
Nnamdi
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Oct 19, 2006 @ 6:06 am
Thanks for the article,it was very helpful in the course of my research.
Please do keep me posted on more information concerning health related issues.
L Bernhard
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Jun 22, 2007 @ 8:20 pm
a few years back I had some blood tests done for my arthritis. They came back negative for RH arthritis but positive for HLA B8 and HLA B 27, My doctors say not to worry. I am 59 yrs old and have not developef any of the diseases associated with those markers, should I be concerned? Have I passes these positive blood markers to my son and his children? Any help would be appreciated or any place yuou can direct me to on the web that can clear up the questions I have. Thaks
Paras
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Jul 16, 2007 @ 3:15 pm
I would like to know how one gets an HLA B test for Behcet's and not have it considered experimental?

I understand that this is one of the tests usually done to find if the individual has a predisposition to Behcet's.

What is the CPT code used for this lab test and what is the Dx code for Behcet's a rare immune syndrome/illness/disease?

Thank you
hajer
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Nov 2, 2007 @ 9:09 am
hi iam need more information about hla typing in tuberculosis patient
TSIETSI
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Apr 7, 2008 @ 12:12 pm
Thanx a lot for the insider,it really helped me alot in my research.
SHYAM
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Sep 4, 2008 @ 5:05 am
This is really good and it gave me a good idea about the HLA types. If possible inform me about the chance of a person getting blood exactly like his own. Thank You.
anamika
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Sep 18, 2008 @ 3:03 am
My project topic is HLA Test and this artical is usefull to me. You give me more informetion about analysis of hla. Thank you.
j patel
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May 19, 2009 @ 9:21 pm
This article is excellent!! It really helps one understand the basics of HLA
Deepankar
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Aug 3, 2009 @ 11:23 pm
this is a very good compiled and informative article,thanx i got to know about HLA and now i have a great interest in doing research on this topic.
wasim
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Aug 20, 2009 @ 8:08 am
The article is very good and clears all the doubts of HLA test its very useful information for person going for bone marrow transplant.Its a must to be read article for HLA
Mohmed
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Dec 22, 2009 @ 5:05 am
i want to know the releation between HLA test & association with Rheumatic arthritis
Anand
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Feb 25, 2010 @ 11:23 pm
We are on a bone marrow donor lookout for a transplant. Do both the ABO blood grouping and HLA typing has to match? If ABO blood grouping doesn't match, and HLA Typing does, can he/she be a potential donor?
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Mar 24, 2010 @ 9:21 pm
The ABO and HLA high res (very specific) have to match for a bone marrow donor. Bone Marrow it the most specific match concerning transplants. O is the universal donor for A B O and AB...
A into A
B into B
either A,B,AB into AB
O into either A, B, AB
very rare A2 into O.
There is also antibody testing to make sure the recip does not have antibody to the donor's DNA.
HLA, ABO, antibodies, body type, condition of the organ, and immunosuppressant drugs are all key factors that play a huge roll in immune response and how well the transplant is accepted :)
Hope that helps (HLA Technologist)
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Jun 21, 2010 @ 11:23 pm
I do CDC-based cross-match test (for kidney transplantation recipients) in my lab too, but with little verification, because of the lack of well trained technicians/specialists.
Could you please help me find an updated protocol for CDC-based cross-match test, with emphasis on the following, 1) controls (especially positive control: what reagents, how to purchase, etc.); and, 2) AHG cross-match protocol (using anti human globulin - AHG, to improve the sensitivity of the test).
Thank you very much.
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Oct 12, 2010 @ 6:06 am
I just found out i test positive for HLA antibodies. what do i do next? do i need to worry?
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Jan 26, 2011 @ 2:02 am
nice information and verey usefull but i need to know abrivetion about HLA -DR,DP, DQ WITH THANKS
david
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Feb 15, 2011 @ 12:12 pm
A ex girlfriend told me that she brought someone else's child to test during a paternity dispute, is this possible or would this test show if the child did not belong to her as well?
maitrik
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Apr 2, 2011 @ 4:04 am
Please give in detail of RBC antigen typing detail and its significance. how to aware routine blood donors for typing.
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May 12, 2011 @ 10:22 pm
i have the hla-b27 syndrome is the any way that i got it from a bone that i had put in my neck after a car wreck, if there is anyone that know's this new to me and i did'nt have any problems until after the surgery
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Oct 13, 2011 @ 6:18 pm
Is there an entity out there that would consider doing an antigen screening on me at no cost in the NYC area and allowing me a copy of the results? I believe I am Type 0+Rh+ and according to this article a potentially useful donor match for a wide variety of recipients.
Suma
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Jul 23, 2012 @ 10:10 am
This article is indeed very useful! Thank you very much :)
sobita
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Sep 24, 2012 @ 7:07 am
i want to know about human leukocyte assay...can anyone help me regarding this?
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Nov 13, 2012 @ 12:00 am
do all hla tests take around two weeks? (bone marrow transplant - aplastic anemia)
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Mar 22, 2013 @ 3:03 am
Iam expert and specialist in HLA system having more than 40 years of experience in this field.Through out my whole carrer I worked in the field of TRANSPLANT IMMUNOLOGY in routine as well as in research. I know the minute comlications in this field because I used to prepare each solutions and reagents or other material my self. If any body wants to ask any question relating to HLA ,weather it is for Renal transplant or Bone Marrow Transplant can ask. I am at present working with the world class laboratory of Stem Cell Processing and Bone Marrow Transplant Laboratory, where I am engaged in Autolous Stem cell Collection,Processing(Flow Cytometry, Clonogenic Assay) Slow rate Freezing and Preservation. And at the time of Transplant(Infusion) Processing for Thawing .
Susan
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Jun 1, 2013 @ 12:12 pm
How long does the test take to determine if a donor is a match? From the time the blood sample is taken to results of the HLA PCR test?

Thank you!
Khaled
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Jul 7, 2013 @ 3:15 pm
hi\
a lot of useful information but i wanna to know why is the HLA not found on mature sperm and brain cells ?
and what are the clinical applications ?
thank you.
hasan
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Oct 29, 2013 @ 6:18 pm
I am possitive with HLA B27.
Can I donate Kidney.
mi
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Feb 22, 2014 @ 1:01 am
How long does it take to get the result of the test.thank you
jim cleary
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Aug 1, 2014 @ 11:11 am
What would happen if, by human error, a heart was transplanted with HLA antibodies incompatible with the recipient's body?

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