The Short Story of HLA and Its Methods

BACKGROUND: During the past 40 years, typing for the human leukocyte antigens (HLA) was done using serological techniques. Several improvements were achieved as to the efficiency and reliability of these techniques. One of the major drawbacks of serology, however, is the need of viable cells. Especially blood cells drawn from deceased donors, as are the usual source for typing of corneal donors, may have a grossly impaired viability and a reduced expression of antigens on their cell surface. This makes serological typing difficult and liable to errors. In the mid-1980s, molecular typing was first introduced in many laboratories. This first period dealt with the so-called restriction fragment length polymorphism method, a tedious method not suited for prospective typing. Only with the introduction of the polymerase chain reaction was the suitability of molecular techniques with respect to perspective typing achieved. METHODS: International workshops and the effort of many laboratories led to a standardization of the methods. External proficiency testing exercises on transplantation relevant procedures in the laboratories affiliated to transplantation centers and the introduction of an accreditation system in the USA and in Europe increased significantly the reliability of all relevant immunogenetical testing. RESULTS: To date, patients and prospective organ and tissue donors are typed in addition to serology also with molecular methods. Using these techniques, the reliability and reproducibility of HLA typing have reached levels of more than 98%. Even 8-day-old peripheral blood samples can now be typed routinely with these methods, formerly impossible by serology. CONCLUSION: The laboratories affiliated to the transplantation centers are ready for high reliability testing of all HLA markers required by the clinic according to the results of controlled clinical long-term follow-up studies.