598
JIO 1992; 165 (March)
Correspondence
Human Leukocyte Antigen, Tuberculosis, and Mycobacterium tuberculosis-Specific Antibody
Table I. Association between HLA (human leukocyte antigen) class II alleles and tuberculosis. % positive for serotype
Colleagues- We reported the association of human leukocyte
Graham H. Bothamley and Geziena M. T. Schreuder MRC Tuberculosis and Related Injections Unit. Royal Postgraduate Medical School. London. United Kingdom. and Department of Inununohaentatologv and Bloodbank, University Hospital, Leiden, Netherlands Correspondence: Dr. G. H. Bothamley, MRC Tuberculosis and Related Infections Unit, Royal Postgraduate Medical School, Oucane Road. London W 12 OHS. UK. The Journal of Infectious Diseases 1992;165:598 © 1992 by The University of Chicago. All rights reserved. 0022-1899/92/6503-0042$01.00
AlIele*
(n= 101)
Controls (n = 64)
ORwl5 DRwl6 DQw2 DQw5 t DQw6 DQw7 DQw8 DQw9
53 3 17 42 39 62 4 I
29 3 25 33 17 83 2 3
Patients
x2
RR
AR/PF
95%CI
9.lt 0.01 1.7 1.2 3.9 7.7 t
2.77 0.89 0.61 1.44 2.07 0.35 1.94 0.37
0.34 NO NO NO NO -0.54 NO NO
0.16.0.43 ND ND NO ND -0.19. -0.76 ND ND
0.6 1.2
NOTE. RR = relative risk; AR = attribute risk; PF = preventive fraction (negative values); CI = confidence intervals; ND = not done as x 2 test not significant. * Serologic typing for DQw4 was not available. t PCOIT < .05 (P corr = probability value corrected for the number of informative comparisons [I D. t DQw5 could not be defined in DQw6+ individuals. Significant association between DQw5 and tuberculosis would occur only if all DQw6- patients (n = 14) and no DQw6- controls (n = 3) were DQw6.DQw5.
References I. Bothamley GH. Swanson Beck J. Schreuder GMT, et al. Association of tuberculosis and M. tuberculosis-specific antibody levels with HLA. J Infect Dis 1989; 159:549-55. 2. Bodmer WF. Albert E. Bodmer JG. et al. Nomenclature for factors ofthe HLA system. 1987. In: Dupont B. ed. Immunobiology ofHLA. Vol I. New York: Springer-Verlag. 1989:72-9. 3. Bodmer JG. Marsh SGE, Parham P. et al. Nomenclature for factors of the HLA system. 1989. Immunobiology 1990; 180:278-93. 4. Gao X. Serjeantson SW. Heterogeneity in HLA-DR2-related DR,DQ haplotypes in eight populations of Asia-Oceania. Immunogenetics (in press). 5. Khomenko AG. Litvinov VI. Chukanova VP. Pospelov LE. Tuberculosis in patients with various HLA phenotypes. Tubercle 1990;71: 187-92. 6. Brahmajothi V. Pitchappan RM. Kakkanaiah VN. et al. Association of pulmonary tuberculosis and HLA in South India. Tubercle 1991;72:123-32. 7. Hawkins BR. Higgins DA, Chan SL. Lowrie DB, Mitchison DA, Girling OJ. HLA typing in the Hong Kong Chest Service/British Medical Research Council study of factors associated with the breakdown to active tuberculosis of inactive pulmonary lesions. Am Rev Respir Dis 1988;138:1616-21. 8. Schreuder GMT. van den Berg-Loonen PM. Verduyn W. et al. Increasing complexity ofHLA-DR2 as detected by serology and oligonucleotide typing. Hum Immunol 1991;12 (in press).
Downloaded from http://jid.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on August 1, 2015
antigen (HLA)-DR2 and DQw I with smear-positive pulmonary tuberculosis [l] but at that time could not determine whether the DR or the DQ locus held the more significant association. Since then, two histocompatability workshops have established the role of the 2B3 and TAl 0 specificities and have permitted the distinction ofDRwl5 and DRwl6 in DR2 [2,3]. In our study population, DRw 15 was equally associated with DQw5 (n = 26) and DQw6 (n = 23), while DRw 16 was associated with DQw5 (n = 3); these relationships have been confirmed by DNA typing in other Indonesian populations [4] (unpublished data). The data now suggest that the dominant association between HLA and tuberculosis is with DRw 15 (table I). Antibody levels to the TB71 and TB72 epitopes of the 38kDa antigen of Mycobacterium tuberculosis remained significantly higher in DRw 15-positive than in DRw 15-negative individuals (P < .00 I). Antibody levels >25 to the TB7 I and TB72 epitopes were more frequent in DRwI5,DQw5 individuals than in individuals without this phenotype (x 2 = 8.4 and 5.0, respectively; P < .05), while no significant difference in frequency was observed for the DRw 15,DQw6 haplotype (subjects apparently homozygous for DRwI5,DQw6 were excluded as DQw5 could not be defined in the presence of DQw6). However, in Indonesian populations, DQw5 may occur in combination with several different DRwl5 DRBJ. DRB5. and DQAJ genotypes [4). The basis of increased immune responsiveness to the 38-kDa antigen cannot therefore be defined as yet. The association between tuberculosis and HLA-DR2 has been confirmed in other studies in which the control population has been exposed to tuberculosis [5, 6] but was not apparent in Hong Kong [7). In view of the increasing number of possible DR2+ haplotypes [8], we suggest that oligonucleotide typing will become increasingly important in examining the relationship between HLA and tuberculous and immune responsiveness to M. tuberculosis-specific antigens.
JIO 1992; 165 (March)
Correspondence
Human Leukocyte Antigen, Tuberculosis, and Mycobacterium tuberculosis-Specific Antibody
Table I. Association between HLA (human leukocyte antigen) class II alleles and tuberculosis. % positive for serotype
Colleagues- We reported the association of human leukocyte
Graham H. Bothamley and Geziena M. T. Schreuder MRC Tuberculosis and Related Injections Unit. Royal Postgraduate Medical School. London. United Kingdom. and Department of Inununohaentatologv and Bloodbank, University Hospital, Leiden, Netherlands Correspondence: Dr. G. H. Bothamley, MRC Tuberculosis and Related Infections Unit, Royal Postgraduate Medical School, Oucane Road. London W 12 OHS. UK. The Journal of Infectious Diseases 1992;165:598 © 1992 by The University of Chicago. All rights reserved. 0022-1899/92/6503-0042$01.00
AlIele*
(n= 101)
Controls (n = 64)
ORwl5 DRwl6 DQw2 DQw5 t DQw6 DQw7 DQw8 DQw9
53 3 17 42 39 62 4 I
29 3 25 33 17 83 2 3
Patients
x2
RR
AR/PF
95%CI
9.lt 0.01 1.7 1.2 3.9 7.7 t
2.77 0.89 0.61 1.44 2.07 0.35 1.94 0.37
0.34 NO NO NO NO -0.54 NO NO
0.16.0.43 ND ND NO ND -0.19. -0.76 ND ND
0.6 1.2
NOTE. RR = relative risk; AR = attribute risk; PF = preventive fraction (negative values); CI = confidence intervals; ND = not done as x 2 test not significant. * Serologic typing for DQw4 was not available. t PCOIT < .05 (P corr = probability value corrected for the number of informative comparisons [I D. t DQw5 could not be defined in DQw6+ individuals. Significant association between DQw5 and tuberculosis would occur only if all DQw6- patients (n = 14) and no DQw6- controls (n = 3) were DQw6.DQw5.
References I. Bothamley GH. Swanson Beck J. Schreuder GMT, et al. Association of tuberculosis and M. tuberculosis-specific antibody levels with HLA. J Infect Dis 1989; 159:549-55. 2. Bodmer WF. Albert E. Bodmer JG. et al. Nomenclature for factors ofthe HLA system. 1987. In: Dupont B. ed. Immunobiology ofHLA. Vol I. New York: Springer-Verlag. 1989:72-9. 3. Bodmer JG. Marsh SGE, Parham P. et al. Nomenclature for factors of the HLA system. 1989. Immunobiology 1990; 180:278-93. 4. Gao X. Serjeantson SW. Heterogeneity in HLA-DR2-related DR,DQ haplotypes in eight populations of Asia-Oceania. Immunogenetics (in press). 5. Khomenko AG. Litvinov VI. Chukanova VP. Pospelov LE. Tuberculosis in patients with various HLA phenotypes. Tubercle 1990;71: 187-92. 6. Brahmajothi V. Pitchappan RM. Kakkanaiah VN. et al. Association of pulmonary tuberculosis and HLA in South India. Tubercle 1991;72:123-32. 7. Hawkins BR. Higgins DA, Chan SL. Lowrie DB, Mitchison DA, Girling OJ. HLA typing in the Hong Kong Chest Service/British Medical Research Council study of factors associated with the breakdown to active tuberculosis of inactive pulmonary lesions. Am Rev Respir Dis 1988;138:1616-21. 8. Schreuder GMT. van den Berg-Loonen PM. Verduyn W. et al. Increasing complexity ofHLA-DR2 as detected by serology and oligonucleotide typing. Hum Immunol 1991;12 (in press).
Downloaded from http://jid.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on August 1, 2015
antigen (HLA)-DR2 and DQw I with smear-positive pulmonary tuberculosis [l] but at that time could not determine whether the DR or the DQ locus held the more significant association. Since then, two histocompatability workshops have established the role of the 2B3 and TAl 0 specificities and have permitted the distinction ofDRwl5 and DRwl6 in DR2 [2,3]. In our study population, DRw 15 was equally associated with DQw5 (n = 26) and DQw6 (n = 23), while DRw 16 was associated with DQw5 (n = 3); these relationships have been confirmed by DNA typing in other Indonesian populations [4] (unpublished data). The data now suggest that the dominant association between HLA and tuberculosis is with DRw 15 (table I). Antibody levels to the TB71 and TB72 epitopes of the 38kDa antigen of Mycobacterium tuberculosis remained significantly higher in DRw 15-positive than in DRw 15-negative individuals (P < .00 I). Antibody levels >25 to the TB7 I and TB72 epitopes were more frequent in DRwI5,DQw5 individuals than in individuals without this phenotype (x 2 = 8.4 and 5.0, respectively; P < .05), while no significant difference in frequency was observed for the DRw 15,DQw6 haplotype (subjects apparently homozygous for DRwI5,DQw6 were excluded as DQw5 could not be defined in the presence of DQw6). However, in Indonesian populations, DQw5 may occur in combination with several different DRwl5 DRBJ. DRB5. and DQAJ genotypes [4). The basis of increased immune responsiveness to the 38-kDa antigen cannot therefore be defined as yet. The association between tuberculosis and HLA-DR2 has been confirmed in other studies in which the control population has been exposed to tuberculosis [5, 6] but was not apparent in Hong Kong [7). In view of the increasing number of possible DR2+ haplotypes [8], we suggest that oligonucleotide typing will become increasingly important in examining the relationship between HLA and tuberculous and immune responsiveness to M. tuberculosis-specific antigens.
