The frequencies of distribution of 25 Histocompatibility Antigens were determined in 92 Mexican patients with leprosy and compared with those in 315 Mexicans who did not have the disease. No statistically significant differences were found between the patients.
The frequencies of distribution of 25 Histocompatibility Antigens were determined in 92 Mexican patients with leprosy and compared with those in 315 Mexicans who did not have the disease. No statistically significant differences were found between the patients.
The frequencies of distribution of 25 Histocompatibility Antigens were determined in 92 Mexican patients with leprosy and compared with those in 315 Mexicans who did not have the disease. No statistically significant differences were found between the patients.
Histocompatibility Antigens in Patients with Leprosy
Author(s): Thomas H. Rea, Norman E. Levan, Paul I. Terasaki
Source: The Journal of Infectious Diseases, Vol. 134, No. 6 (Dec., 1976), pp. 615-618 Published by: Oxford University Press Stable URL: http://www.jstor.org/stable/30106631 . Accessed: 02/07/2011 02:27 Your use of the JSTOR archive indicates your acceptance of JSTOR's Terms and Conditions of Use, available at . http://www.jstor.org/page/info/about/policies/terms.jsp. JSTOR's Terms and Conditions of Use provides, in part, that unless you have obtained prior permission, you may not download an entire issue of a journal or multiple copies of articles, and you may use content in the JSTOR archive only for your personal, non-commercial use. Please contact the publisher regarding any further use of this work. Publisher contact information may be obtained at . http://www.jstor.org/action/showPublisher?publisherCode=oup. . Each copy of any part of a JSTOR transmission must contain the same copyright notice that appears on the screen or printed page of such transmission. JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org. Oxford University Press is collaborating with JSTOR to digitize, preserve and extend access to The Journal of Infectious Diseases. http://www.jstor.org THE JOURNAL OF INFECTIOUS DISEASES * VOL. 134, NO. 6 * December 1976 c 1976 by the University of Chicago. All rights reserved. Histocompatibility Antigens in Patients with Leprosy Thomas H. Rea, Norman E. Levan, and Paul I. Terasaki From the Section of Dermatology, Department of Medicine, University of Southern California School of Medicine; the Department of Dermatology, Los Angeles County-University of Southern California Medical Center; and the Department of Surgery, University of California School of Medicine, Los Angeles, California The frequencies of distribution of 25 histocompatibility antigens were determined in 92 Mexican patients with leprosy and compared with those in 315 Mexicans who did not have the disease. No statistically significant differences were found between the patients and the controls in regard to histocompatibility antigens, and subgroups with a significant difference could not be identified by division of the patients accord- ing to the density of Mycobacterium leprae or the presence or absence of cell-medi- ated immunity directed against antigens of M. leprae. Genetic factors are considered to be important in leprosy and influence both susceptibility to the disease and its mode of expression [1]. Im- munologic factors are also considered impor- tant in leprosy; observations of impaired cell-me- diated immunity can be interpreted as signifying that immune responses determine susceptibility and mode of expression [2]. These immunologic factors may be genetic, and there is increasing evidence that specific immune response (Ir) genes control responses critical for susceptibility to disease and that these Ir genes are associated with the major histocompatibility system, HL-A [3]. Several diverse diseases already have been shown to be associated with HL-A antigens [3]. Some of these diseases are clearly genetic, such as psoriasis [4], and others are associated with characteristic immunologic responses, such as dermatitis herpetiformis [5]. It is logical that HL- A associations with leprosy have been sought. Such searches are based on the hypothesis that susceptibility to leprosy (and/or its mode of expression) is determined by an immunologic response (or lack thereof) directly regulated by Received for publication March 8, 1976, and in revised fornm June 8, 1976. Access to the patients of the U.S. Public Health Service Clinic in San Pedro, California was graciously provided by Drs. Charles Buhrow, Margaret Storkan, and Carl Korn. Please address requests for reprints to Dr. Thomas H. Rea, Department of Dermatology, Los Angeles County- University of Southern California Medical Center, 1200 North State Street, Los Angeles, California 90033. an Ir gene. The finding of a statistically signifi- cant difference in the distribution of HL-A anti- gens between patients and controls would be evi- dence supporting the Ir gene hypothesis in sus- ceptibility to leprosy. This paper is a report of a study of HL-A anti- gens in Mexican-born patients with leprosy. Materials and Methods All 92 patients with leprosy were born in Mexico or were of bilateral Mexican descent. The diag- nosis of leprosy was confirmed histologically in each case. Forty-four patients were from the Los Angeles County-University of Southern Califor- nia Medical Center; 41 from the U.S. Public Health Service Clinic in San Pedro, Calif.; two from the private practice of Dr. Ronald Smits in Los Angeles, Calif.; and five from the private practice of one of us (N.E.L.). Blood relatives were not included in the study. Controls were 315 individuals from Mexico or of Mexican ances- try. For classification the seven-group system of Ridley and Waters [6] was used, and individual classifications were made on the basis of clinical manifestations and biopsy index: TT, polar tu- berculoid; TI, subpolar tuberculoid; BT, border- line with tuberculoid features; BB, borderline; BL, borderline with lepromatous features; LI, subpolar lepromatous; LL, polar lepromatous. Three groupings were made for analysis of the data. In the first grouping controls were com- pared with all patients with leprosy. In the sec- 615 616 Rea, Levan, and Terasaki ond grouping controls were compared with pa- tients with many bacilli (one or more per 10 oil- emersion fields of a histologic slide from involved skin, BB-LL) and with patients with few bacilli (less than one per 10 oil-emersion fields, TT-BT). In the third grouping controls were compared with patients having some cell-mediated immunity to Mycobacterium leprae (TT-LI) and with pa- tients having no cell-mediated immunity to M. leprae (LL), as inferred from classification accord- ing to the system of Ridley and Waters [6]. HL-A antigens were identified by the microlym- phocytotoxic technique as previously described [7]. Our results are recorded to conform to re- cently adopted nomenclature [8]. The results from other studies cited are recorded as pub- lished. Results The distribution of HL-A antigens is summar- ized in table 1. Using a x2 test with Yates' correc- tion, we obtained an uncorrected P value of <0.05 under the following circumstances: HLA- B13 is more frequent in LL and LL-BB pa- tients than in controls; W16 is more frequent in LI-TT patients than in controls; HLA-BW21 is less frequent in all leprosy patients than in con- trols. These differences are not statistically sig- nificant when the P value is multiplied by 25, the number of specificities tested. Discussion In previous studies of HL-A antigens, summarized in table 2, Escobar-Gutierrez et al. [9] found a Table 1. Frequencies of the distribution of 25 histocompatibility antigens (HL-A) in 92 Mexican patients with leprosy and in 315 Mexicans who did not have leprosy (controls). All leprosy LL-BB BT-TT LL LI-TT HL-A (old nomenclature) patients (92) patients (82) patients (10) patients (72) patients (20) Controls HLA-A1 (HL-A1) 13 15 0 17 0 16 HLA-A2 (HL-A2) 54 56 40 54 55 48 HLA-A3 (HL-A3) 14 13 20 15 10 13 HLA-AW23 (W23) 3 4 0 3 5 6 HLA-AW24 (W24) 23 23 20 22 25 22 HLA-A10 (HL-A10) 9 6 30 4 25 12 HLA-All (HL-A11) 15 15 20 15 15 12 HLA-A28 (W28) 15 13 30 15 15 16 HLA-A29 (W29) 7 7 0 8 0 9 HLA-AW30 (W30) 24 26 10 25 20 19 HLA-AW32 (W32) 3 2 10 1 10 4 HLA-B5 (HL-A5) 15 16 10 17 10 15 HLA-B7 (HL-A7) 9 9 10 10 5 15 HLA-B8 (HL-A8) 5 6 0 7 0 8 HLA-B12 (HL-A12) 23 26 0 25 15 24 HLA-B13 (HL-A13) 5 6* 0 6* 5 1 HLA-BW35 (W5, Te50) 34 35 20 32 40 30 HLA-BW22 (W22) 5 5 10 4 10 5 HLA-B27 (W27) 1 1 0 1 0 5 HLA-B14 (W14) 14 12 30 11 25 13 HLA-BW15 (W15) 5 5 10 6 5 7 HLA-B18 (W18) 3 4 0 3 5 9 HLA-BW40 (W10, Te60) 15 15 20 15 15 14 W16 24 21 40 19 35* 15 HLA-BW21 (W21) 3* 4 0 4 0 11 NOTE. LL-BB = polar lepromatous, borderline; BT-TT = borderline with tuberculoid features, polar tuberculoid; LL = polar lepromatous; and LI-TT = subpolar lepromatous, polar tuberculoid. LL-BB patients were considered to have many bacilli and BT-TT to have few. LL patients" were considered to have no cell-mediated immunity to Mycobacterium leprae and LI-TT were considered to have some cell-mediated immunity (see Materials and Methods). Numbers in parentheses are numbers of patients. *P <0.05 (uncorrected). Histocompatibility Antigens in Leprosy 617 Table 2. Summary of studies of typing of histocompatibility antigens (HL-A) in patients with leprosy. No. of No. of specifi- No. of con- cities Ethnic Study patients trols tested group studied Findings Escobar-Gutidrrez et al. [9] 50 200 7 Mexican (mestizo) Low HL-A2 and low HL-A3 Thorsby et al. [2] 39 36 27 Ethiopian (Amharas) Significantly increased W21 in all but LL* patients Smith et al. [10] 82 50 28 Filipino No differences Reis et al. [ 1I] 26 32 23 Brazilian No differences Kreisler et al. [12] 30 149 21 Spanish (Caucasian) Significantly increased HL-A14 especially in lepromatous patients Dasgupta et al. [13] 70 40 11 Indian HL-A9 insignificantly decreased in nonlepromatous, and HL-A8 insignificantly increased in lepro- matous subjects Present study 92 315 25 Mexican No differences *LL = polar lepromatous. decrease in frequency of HL-A2 and HL-A3 when 50 Mexican patients and 200 controls were com- pared in a study of seven HL-A antigens; these investigators stated that technical difficulties with behavior of lymphocytes from some patients with leprosy diminished the forcefulness of their find- ings. Thorsby et al. [2] examined 39 patients and 36 ethnically similar, normal individuals from Ethi- opia for the presence of 27 antigens. (These au- thors used histologic criteria in defining their LL category which made it a more uniform group than ours, as ours undoubtedly contained pa- tients who would be histologically classed as LI; however, their tuberculoid group was probably similar to our BT-TT group.) In patients classed as tuberculoid and "LL + LI," Thorsby et al. [2] found a statistically significant increase in the frequency of antigen cW21, which was absent in LL patients and controls. Smith et al. [10] examined 82 Filipino patients and 50 Filipino controls for the presence of 28 antigens and found no statistically significant dif- ferences in the distributions of antigens. These authors made a distinction between tuberculoid (TT-BT) and lepromatous (BL-LL) conditions that was similar to our distinction between few and many bacilli. Antigen W21 was normally dis- tributed. Reis et al. [11] examined 26 patients and 32 ethnically matched individuals (presumably Bra- zilian) for the presence of 23 antigens and found no statistically significant differences in antigen distribution. Their distinction between leproma- tous and tuberculoid patients was made without explicit criteria; these criteria were presumably similar to those used to make our distinction be- tween few and many bacilli. They did not state whether the W21 antigen was sought. Kreisler et al. [12], who studied Spaniards, found that 30 patients with leprosy had a signifi- cantly higher incidence of HL-A14 than did 149 controls. In this series the high incidence of this antigen was particularly evident in the 17 Mit- suda-negative patients. Dasgupta et al. [13] sought 11 antigens in 70 patients and 40 controls in India. Using criteria similar to ours, they found a statistically insig- nificant, increased frequency of HL-A8 in 40 lepromatous subjects and a statistically insignifi- cant, decreased frequency of HL-A9 in 30 non- lepromatous subjects. The "significant" findings in the studies de- scribed are not uniform. The tentative findings of Escobar-Gutierrez et al. [9] concerning HL-A2 and HL-A3 have not been confirmed in any other study, including ours. The statistically significant distribution of W21 found by Thorsby et al. [2] was not confirmed by Smith et al. [10], Kreisler et al. [12], or us. The high incidence of HL-A14 noted by Kreisler et al. [12] has not been found by any other investigators. Similarly, our own suggestive findings have not been confirmed by others. HLA-B13, perhaps in- 618 Rea, Levan, and Terasaki creased in our LL and LL-BB groups, was absent in the lepromatous patients examined by Thors- by et al. [2] and Smith et al. [10] and present in normal frequency in the studies of Kreisler et al. [12] and Dasgupta et al. [13]. The distribution of W16, perhaps increased in our LI-TT group, was similar in patients and controls in the studies of Thorsby et al. [2] and Smith et al. [10]. HLA- BW21, perhaps increased in all patients with leprosy but absent in the LI-TT and BT-TT groups, was present in increased frequency in the tuberculoid patients reported by Thorsby et al. [2] and in normal frequency in the patients re- ported by Smith et al. [10] and Kreisler et al. [12]. Including the present paper, seven studies of HL-A frequencies in leprosy have been reported. In three of these studies [10, 11], no differences were found; in two [9, 13] equivocal differences were found, and in two other studies [2, 12] sta- tistically significant differences were found. Can these diverse results be reconciled? The "signifi- cant" findings of Thorsby et al. [2] and Kreisler et al. [12] cannot be dismissed easily as a chance mat- ter, but the seven studies collectively provide no evidence that a single HL-A antigen is asso- ciated with susceptibility to leprosy or with a par- ticular clinical expression of leprosy. It is possi- ble that, within particular ethnic groups, a par- ticular HL-A antigen is associated with a particu- lar clinical expression of leprosy; alternatively, the differences among these seven studies may be attributable to chance variations in sampling. References I. Spickett, S. G. Genetic mechanisms in leprosy. In R. G. Cochrane and T. F. Davey [ed.]. Leprosy in theory and practice. 2nd ed. Williams and Wilkins, Balti- more, 1964, p. 98-124. 2. Thorsby, E., Godal, T., Myrvang, B. HL-A antigens and susceptibility to diseases. II. Leprosy. Tissue Antigens 3:373-377, 1973. 3. McDevitt, H. O., Bodmer, W. F. HL-A, immune-re- sponse genes and disease. Lancet 1:1269-1275, 1974. 4. White, S. H., Newcomer, V. D., Mickey, M. R., Terasaki, P. I. Disturbance of HL-A antigen frequency in psori- asis. N. Engl. J. Med. 287:740-743, 1972. 5. Katz, S. I., Falchuk, Z. M., Dahl, M. V., Rogentine, G. N., Strober, W. HL-A8: a genetic link between der- Inatitis herpetiformis and gluten-sensitive enteropa- thy. J. Clin. Invest. 51:2977-2980, 1972. 6, Ridley, D. S., Waters, M. F. R. Significance of varia- tions within the lepromatous group. Lepr. Rev. 40: 143-152, 1969. 7. Mittal, K. K., Mickey, M. R., Sigal, B. P., Terasaki, P. I. Serotyping for homotransplantation. XVIII. Refinement of microdroplet lymphocyte cytotoxici- ty test. Transplantation 6:913-927, 1968. 8. World Health Organization-International Union of Im- munological Societies Terminology Committee. No- menclature for the factors of the HLA system. In S. Kissmeyer-Nielsen [ed.]. Histocompatibility testing. Munksgaard, Copenhagen, 1975, p. 5-11. 9. Escobar-Gutikrrez, A., Gorodezky, C., Salazar-Mall6n, M. Distribution of some of the HL-A system lympho- cyte antigens in Mexicans. Vox Sang. 25:151-155, 1973. 10. Smith, G. S., Walford, R. I., Shepard, C. C., Payne, R., Prochazka, G. J. Histocompatibility antigens in lep- rosy. Vox Sang. 28:42-49, 1975. 11. Reis, A. P., Maia, F., Reis, V. F., Andrade, I. M., Cam- pos, A. A. S. HL-A antigens in leprosy. Lancet 2:1384, 1974. 12. Kreisler, M., Arnaiz, A., Perez, B., Cruz, E. F., Bootello, A. HL-A antigens in leprosy. Tissue Antigens 4:197- 201, 1974. 13. Dasgupta, A., Mehra, N. K., Ghei, S. K., Vaidya, M. C. Histocompatibility antigens in leprosy. Tissue Anti- gens 5:85-87, 1975.