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A CASE STUDY OF A NULL ALLELE, A*2411N, IN THE INTERNATIONAL CELL EXCHANGE.
M. Lau ¹, A.F. Locke ¹, J.M. Cecka ¹, E.F. Reed ¹, A. Smerglia ², G. Teresi ², D.M. Thomas ² and E. Ball ². ¹ UCLA Immunogenetics Center, UCLA, Los Angeles, CA, USA and ² Allogen Laboratories, Cleveland Clinic Foundation, Cleveland, OH, USA .

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Since 1974, the International Cell Exchange has provided a process to standardize HLA typing on a collaborative basis among laboratories worldwide. The process is simple, that is, 4 cells from healthy normal donors are typed monthly on a blind basis for Class I antigens by serology and, since 1990, also by molecular-based methods.
We report a recent study of a null HLA allele, A*2411N, typed in cell 1229 in March 2005. Lymphocytes isolated from peripheral blood from an Asian Indian individual were typed by 110 serology labs and 43 DNA labs. Consensus results were A30, B13, B57, Cw6 and A*24, A*30, B*13, B*57, Cw*06. Assignments were reported for both null and expressed A24 alleles:

A24	11%	A*2402	16%	A*2411N	24%
A9V	1%	A*240201	2%	A*24null	5%
		A*24020101	2%	A*24	51%

Table 1

The one difference between A*2402 and A*2411N is the insertion of an additional C at the beginning of exon 4, thus changing the reading frame that results in termination at a nonsense codon. Of great concern was that A24 (11%) and A*2402 (20%) were reported for the null A24.
Publications have discussed the probable detrimental effects of missing a null allele in the clinical setting.^4,5 Since the prevalence of HLA null alleles may be 0.3% or higher, each clinical lab should have viable typing strategies in place for the detection of such alleles. The final typing findings of the null allele in this recent case should be cause for consideration for all labs as to whether they would need to modify procedures.
³ Lau M, et al.(2005) Report of the 308th Cell Exchange, April 6, 2005:6,⁴Magor KE et al.(1997) J Immunol 158:5242,⁵Elsner and Blasczyk(2004) Tissue Antigens 64:687