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HLA - SYSTEM

Dr. (Mrs.) Kankonkar

 

HLA stands for Human Leukocyte Antigens and is the Human Major H i s t o c o m p a t i b i l i t y Complex ( MHC ).

HISTORICAL BACKGROUND
The first evidence for the existence for Human Leukocyte Antigens (HLA) in man was obtained in the year 1954 by Jean Dausset in France who observed that patients whose sera contained “Leukoagglutinins” had received a large number
of blood transfusions than those lacking such antibodies. He named them MAC. Rose Pyne et al.4 in USA and Jon van Rood et al in Holland showed simultaneously and in independent studies that pregnancy per se provided an effective stimulus for induction of leukocyte isoantibodies since the mother raises antibodies to the antigens that the foetus has inherited from the father. Sera obtained from such pregnant women provided the most efficient source of HLA reagents.
The concept that the MHC contains Immune Response Genes and HLA is an MHC was formulated in the year 1969 by Devitt and Benacerrof. HLA genes are located on the short arm of Human Chromosome 6 ( 6 p 21.3 ) and are
the most polymorphic genetic complex known so far in the human genomes. These polymorphic genes encode a variety of cell surface molecules called HLA.
 
IMPORTANCE OF HLA
This system plays major role in the regulation of immune system that is self / non-self recognition. In more modern times, the HLA system is extremely important for organ and bone marrow transplantation. HLA genes signi.cantly impact
patients involved in transplantation. Clinically, HLA typing is of greatest importance in organ transplantation, where the determination of the donor and recipient tissue typing of HLA loci is done to ensure the best outcome through minimizing
the risk of graft rejection. This is particularly important in bone marrow transplantation where the graft itself has immune activity. The goal in the transplantation is to accurately match HLA antigen variability of the donor and patient to achieve the highest clinical success.

GENES AND ALLELES ARE IN HLA
HLA region is divided into two classes on the basis of their function viz. Class I which encompasses the HLA A,B and C and Class II which includes the HLA DR, DQ and DP. Each person can have 6 class I and II molecules, respectively, three from each parent. About 1400 alleles are known to be existing at class I and II loci.

TYPING HLA ANTIGENS
The polymorphism of HLA molecule is determined by serology, cellular and molecular methods. However, serology and molecular techniques are widely used. As far as accuracy is concerned molecular typing is the best and reproducible. Recently, DNA based molecular typing has largely replaced serology typing in most parts of the world. Because molecular methods allow identification of alleles which are not determined by serology and compromised by low expression of HLA molecules in some patients. O.ate anti HLA sera of required speci.cities are not available due
to non-availability of multiparous women who are the source of HLA sera. Hence, all antigen speci.cities are not available all the time to meet international standards.

USES OF HLA TYPING
A. Immunological Donor Selection for :
1. Solid organ transplantation viz. kidney, liver and heart.
2. Bone marrow transplantation.
3. Blood component therapy.
B. Clinical Aids in the:
1. Diagnosis of diseases (spondylosis, diabetes mellitus etc.).
2. Prediction of risk for disease development in families.
3. Possible prognosis of certain diseases.
4. Paternity testing .

MOLECULAR TYPING
Over the past several years, molecular techniques to determine HLA type have largely displaced the original serological methods. This has led to greater powers of discrimination of tissue types (HLA alleles) and the discovery of hundreds of previously undescribed alleles. Serological methods are based on an antibody reaction against an epitope on the
HLA molecules and therefore this technique has limited powers of resolution due to the inconsistent performance and limited target . In general, molecular techniques allow better discrimination. The field of molecular biology has shown that
HLA antigens are more complex than we had initially thought. If we take this into account we need to alter conventional antigen counting. Molecular matching must be developed for the following reasons:

1. There is extensive evidence showing that the serological response to allograft ranges far wider than the narrower speci.cities recognized today for HLA matching. Many antibodies against the broad specificities are probably directed against epitopes which are just as immunologic as those directed to the specific cities.
2. The concept of single mismatch between 2 HLA specificities is no longer tenable. Obviously, many incompatibilities exist among the speci.cities.
 

CHOLESTEROL LOWERING IN PATIENTS WITH DIABETES

`Cholesterol lowering statin therapy can produce substantial reductions in the risk of heart attacks, of strokes, and of revascularisations in people with diabetes'

Although plasma LDL cholesterol concentrations among people with and without diabetes are generally similar, individuals with diabetes are at raised risk of cardiovascular disease. Limited evidence on the effects of cholesterol-lowering therapy mean that most patients with diabetes do not receive this treatment. The Heart Protective Study Collaborative Group investigated whether statin treatment is bene.cial compared with placebo among patients with diabetes. For statin-treated patients signi.cant
reductions were seen for major coronary events, strokes, and revascularisation, even if manifest coronary disease was not present. The investigators suggest that statin therapy should be considered routinely for patients with diabetes at high risk of major vascular events, irrespective of initial cholesterol concentration. In a Commentary, Lars Lindholm asks whether this approach should be taken one step further, and all patients with type 2 diabetes should be given a statin, irrespective of cholesterol concentration.

Lancet, 2003; 2000, 2005.



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