CONCISE COMMUNICATIONS 2. Byers VS, Henslee PJ, Kernan NA, Blazar BR, Gingrich R, Phillips GL, LeMaistre CF, Gilliland G, Antin JH, Martin P, Tutscha PJ, Trown P, Ackerman SK,O’Reilly RJ, Scannon PJ: Use of an anti-pan T-lymphocyte rich A chain immunotoxin in steroid-resistant acute graft-versus-host disease. Blood 75:1426, 1990
3. Martin PJ, Hansen JA, Siadak AW, Nowinski RC: Monoclonal antibodies recognizing normal human T lymphocytes and malignant human B lymphocytes: a comparative study. J lmmunol 127:1920, 1981 4. Wofsy D, Seaman WA: Reversal of advanced murine lupus in NZB/NZW F, mice by treatment with monoclonal antibody to L3T4. J Immunol 138:3247, 1987 5. Burastero SE, Casali P, Wilder RL, Notkins AL: Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis. J Exp Med 168: 1979, 1988 6. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RI: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25: 1271-1277, 1982
Does tumor necrosis factor protect against lupus in West Africans? In marked contrast t o the high prevalence of systemic lupus erythematosus (SLE) among North American blacks (I), SLE appears to be uncommon in West Africans. Over a 1-year period at a teaching hospital in Ibadan, Nigeria, which serves a population of more than 2 million, only 1 case of SLE was observed. A previous study in the region (2) documented that only 2 patients with SLE were admitted to the teaching hospital over a 20-year period. Community-based studies by myself and others (2,3) have not identified any patients with SLE (including mild cases) who have not presented at the hospital. These results suggest an incidence and prevalence of SLE substantially lower than those in white populations (1). It is not likely that underdiagnosis is a factor, since the observations have been made by experienced physicians who have had access to adequate facilities for diagnostic investigation. The findings are of particular interest in view of the fact that most blacks in North America and the Caribbean are of West African descent. It has been previously suggested that this difference in SLE occurrence between North American and West African blacks may arise as a result of a protective effect afforded by some parasitic infections, in particular, malaria (3). This hypothesis was based on animal studies which showed that New Zealand mice could be protected against the development of lupus-like disease by infection with Plasmodium berghei (4). A mechanism for this effect has not been elucidated to date, but recent investigations ( 5 ) have raised various possibilities, including a role for tumor necrosis factor a (TNFa) (6). It is now believed that much of the pathologic process associated with malaria is due to the uncontrolled production of TNFa, since it has been demonstrated that this cytokine is induced by malarial antigens (7). Mice that are poor producers of T N F and are predisposed to lupus nephritis can be protected by injections of T N F (8). There is also evidence from studies of humans that T N F a production from mononuclear cells is impaired in some SLE patients (bearing DR2, DQw 1 haplotypes) (9,lO).
839
If blacks are predisposed to the development of lupus or aspects of the disease such as lupus nephritis (11, it is conceivable that over time, repeated malarial antigenic stimulation and consequent T N F a induction provides a protection against lupus in malaria-endemic West Africa. There are conflicting reports with regard to the production of T N F in SLE (lo), and this may reflect the wide clinicopathologic spectrum of the disease, as well as our inability to determine any primary site for the disease and associated local TNF production. The optimal level of T N F and the integrity of the associated regulatory mechanisms are also of probable importance. Even if it could be convincingly shown that the difference in the prevalence of S L E between North American blacks and West Africans was due only to an evolved difference in the prevalence of SLE susceptibility genes, the fact that the genes for T N F map within the major histocompatibility complex raises the possibility of a potential relationship with this cytokine (6,9). Furthermore, it has been suggested that an abnormal T N F gene may be involved in the pathogenesis of autoimmune disease (6). An association between SLE and malaria must remain speculative for the time being, until it can be confirmed through longitudinal studies correlating an increase in the incidence of SLE with increased control of malaria in the West African population. However, the extremely low prevalence of SLE among West Africans requires an explanation, and a protective effect involving T N F merits consideration. Adewale 0. Adebajo, MD Addenhrooke’s Hospital Cambridge, England 1. Siege1 M, Lee SL: The epidemiology of systemic lupus erythe-
matosus. Semin Arthritis Rheum 3:l-53, 1973 2. Greenwood BM: Autoimmune disease and parasitic infections in Nigerians. Lancet I:380-382, 1%8 3. Greenwood BM, Herrick EM, Voller A: Can parasitic infection suppress autoimmune disease? Proc R SOCMed 63: 19-20. 1970 4. Greenwood BM, Herrick EM, Voller A: Suppression of autoimmune disease in NZB and (NZB x NZW) F, hybrid mice by infection with malaria. Nature 226:26&267, 1970 5. Butcher GA, Clark IA: S L E and malaria: another look at an old idea. Parasitol Today 6:259-261, 1990 6. Muller U, Jongeneel CV, Nedospasov SA, Lindahl KF, Steinmetz M: Tumour necrosis factor and lymphotoxin genes map close to H-2D in the mouse major histocompatibility complex. Nature 325:265-267, 1987 7. Bate CAW, Taverne J, Playfair JHL: Soluble antigens are toxic and induce the production of tumour necrosis factor in vivo. Immunology 66:600405, 1989 8. Jacob CO, McDevitt HO: Tumour necrosis factor-a in murine autoimmune ‘lupus’ nephritis. Nature 331:35&358, 1988 9. Jacob CO, Fronek ZL, Lewis GD, Koo M, Hansen JA, McDevitt HO: Heritable major histocompatibility complex class 11associated differences in production of tumour necrosis factor a : relevance to genetic predisposition to systemic lupus erythematosus. Proc Natl Acad Sci USA 87:1233-1237, 1990 10. Yu CL, Chang KL, Chiu CC, Chiang BN, Han SH, Wang SR: Defective phagocytosis, decreased tumour necrosis factor-a production and lymphocyte hyporesponsiveness predispose patients with systemic lupus erythematosus to infection. Scand J Rheumatol 18:97-105, 1989
3. Martin PJ, Hansen JA, Siadak AW, Nowinski RC: Monoclonal antibodies recognizing normal human T lymphocytes and malignant human B lymphocytes: a comparative study. J lmmunol 127:1920, 1981 4. Wofsy D, Seaman WA: Reversal of advanced murine lupus in NZB/NZW F, mice by treatment with monoclonal antibody to L3T4. J Immunol 138:3247, 1987 5. Burastero SE, Casali P, Wilder RL, Notkins AL: Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis. J Exp Med 168: 1979, 1988 6. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RI: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25: 1271-1277, 1982
Does tumor necrosis factor protect against lupus in West Africans? In marked contrast t o the high prevalence of systemic lupus erythematosus (SLE) among North American blacks (I), SLE appears to be uncommon in West Africans. Over a 1-year period at a teaching hospital in Ibadan, Nigeria, which serves a population of more than 2 million, only 1 case of SLE was observed. A previous study in the region (2) documented that only 2 patients with SLE were admitted to the teaching hospital over a 20-year period. Community-based studies by myself and others (2,3) have not identified any patients with SLE (including mild cases) who have not presented at the hospital. These results suggest an incidence and prevalence of SLE substantially lower than those in white populations (1). It is not likely that underdiagnosis is a factor, since the observations have been made by experienced physicians who have had access to adequate facilities for diagnostic investigation. The findings are of particular interest in view of the fact that most blacks in North America and the Caribbean are of West African descent. It has been previously suggested that this difference in SLE occurrence between North American and West African blacks may arise as a result of a protective effect afforded by some parasitic infections, in particular, malaria (3). This hypothesis was based on animal studies which showed that New Zealand mice could be protected against the development of lupus-like disease by infection with Plasmodium berghei (4). A mechanism for this effect has not been elucidated to date, but recent investigations ( 5 ) have raised various possibilities, including a role for tumor necrosis factor a (TNFa) (6). It is now believed that much of the pathologic process associated with malaria is due to the uncontrolled production of TNFa, since it has been demonstrated that this cytokine is induced by malarial antigens (7). Mice that are poor producers of T N F and are predisposed to lupus nephritis can be protected by injections of T N F (8). There is also evidence from studies of humans that T N F a production from mononuclear cells is impaired in some SLE patients (bearing DR2, DQw 1 haplotypes) (9,lO).
839
If blacks are predisposed to the development of lupus or aspects of the disease such as lupus nephritis (11, it is conceivable that over time, repeated malarial antigenic stimulation and consequent T N F a induction provides a protection against lupus in malaria-endemic West Africa. There are conflicting reports with regard to the production of T N F in SLE (lo), and this may reflect the wide clinicopathologic spectrum of the disease, as well as our inability to determine any primary site for the disease and associated local TNF production. The optimal level of T N F and the integrity of the associated regulatory mechanisms are also of probable importance. Even if it could be convincingly shown that the difference in the prevalence of S L E between North American blacks and West Africans was due only to an evolved difference in the prevalence of SLE susceptibility genes, the fact that the genes for T N F map within the major histocompatibility complex raises the possibility of a potential relationship with this cytokine (6,9). Furthermore, it has been suggested that an abnormal T N F gene may be involved in the pathogenesis of autoimmune disease (6). An association between SLE and malaria must remain speculative for the time being, until it can be confirmed through longitudinal studies correlating an increase in the incidence of SLE with increased control of malaria in the West African population. However, the extremely low prevalence of SLE among West Africans requires an explanation, and a protective effect involving T N F merits consideration. Adewale 0. Adebajo, MD Addenhrooke’s Hospital Cambridge, England 1. Siege1 M, Lee SL: The epidemiology of systemic lupus erythe-
matosus. Semin Arthritis Rheum 3:l-53, 1973 2. Greenwood BM: Autoimmune disease and parasitic infections in Nigerians. Lancet I:380-382, 1%8 3. Greenwood BM, Herrick EM, Voller A: Can parasitic infection suppress autoimmune disease? Proc R SOCMed 63: 19-20. 1970 4. Greenwood BM, Herrick EM, Voller A: Suppression of autoimmune disease in NZB and (NZB x NZW) F, hybrid mice by infection with malaria. Nature 226:26&267, 1970 5. Butcher GA, Clark IA: S L E and malaria: another look at an old idea. Parasitol Today 6:259-261, 1990 6. Muller U, Jongeneel CV, Nedospasov SA, Lindahl KF, Steinmetz M: Tumour necrosis factor and lymphotoxin genes map close to H-2D in the mouse major histocompatibility complex. Nature 325:265-267, 1987 7. Bate CAW, Taverne J, Playfair JHL: Soluble antigens are toxic and induce the production of tumour necrosis factor in vivo. Immunology 66:600405, 1989 8. Jacob CO, McDevitt HO: Tumour necrosis factor-a in murine autoimmune ‘lupus’ nephritis. Nature 331:35&358, 1988 9. Jacob CO, Fronek ZL, Lewis GD, Koo M, Hansen JA, McDevitt HO: Heritable major histocompatibility complex class 11associated differences in production of tumour necrosis factor a : relevance to genetic predisposition to systemic lupus erythematosus. Proc Natl Acad Sci USA 87:1233-1237, 1990 10. Yu CL, Chang KL, Chiu CC, Chiang BN, Han SH, Wang SR: Defective phagocytosis, decreased tumour necrosis factor-a production and lymphocyte hyporesponsiveness predispose patients with systemic lupus erythematosus to infection. Scand J Rheumatol 18:97-105, 1989
