- Email: [email protected]
Transfusion with blood from people with HFE gene mutations
2,3,7,8-tetrachlorodibenzo-p-dioxin. J Natl Cancer Inst 1999; 91: 779–86. 3 Fingerhut MA, Halperin WE, Marlow DA, et al. Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. N Engl J Med 1991; 324: 212–18.
Atopy, hygiene, and anthroposophic lifestyle Sir—Johan Alm and colleagues (May 1, p 1485)1 report that atopy was rare in children from Swedish families who had an anthroposophic lifestyle. They speculate that failure of immunisation against measles, increased exposure to childhood infections, or dietary habits that affect the intestinal microflora may have contributed to the reduced risk of atopy. Their intriguing findings, however, are insufficient to test a specific aetiological hypothesis.2 Indeed, studies on a putative protective effect of childhood infections are still in their infancy and inconsistencies among initial observations must be remembered. 2 We reported a low prevalence of atopy among Italian military students exposed to the hepatitis A virus (HAV),3 which is a good marker of low hygienic standards. After that study, we tested the putative HAV-atopy inverse relation in another setting. We took advantage of a previous survey by Stroffolini and colleagues 4 on HAV seroprevalence in the adult general population of the Republic of San Marino, an independent state with 26 000 inhabitants (in 1998) that is completely surrounded by Northern Italy. Serum samples were collected during 1990–91 by a random-sample procedure (1527 men and women aged 肁20 years) and HAV antibodies were tested by E L I S A . 4 In 1509 (98·8%) of the serum sample, IgE against common airborne allergens were measured by a multi-radioallergosorbent assay as previously described; 3 a cut-off of logarithm of ratio units greater than 0·8 was chosen to define atopy. We found that atopy was strongly inversely related to HAV seropositivity: only 61 (6·23%) individuals were atopic among 979 HAV-seropositive participants, compared with 75 (14·15%) among 530 HAV-seronegative participants (p<0·001). The inverse association between HAV and atopy remained significant after adjustment for age and sex by multivariate analysis (odds ratio 0·59 [95% CI 0·38–0·92]). Stratification of data by year of birth showed an increasing trend of atopy among individuals born from 1960
430
onwards.* This trend is almost totally accounted for by individuals never exposed to HAV, because younger participants were less likely to be atopic if they had antibodies against HAV. We speculate that data obtained in San Marino support only one of Alm and colleagues’ suggestions. Indeed, since 1960 there has been an economic “boom” started in the Republic of San Marino, 4 w h e n lifestyle changes produced also a sharp improvement in hygienic standards. Conversely, mass immunisation programmes against measles started in this area (and all over Italy) only in the late 1980s so that measles epidemiology did not substantially change until early 1990s.5 Our data confirm an inverse association in Italy between exposure to HAV and atopy,3 and indicate that factor(s) specifically related to a faecal contamination of the environment, together with unhygienic food handling, may protect from atopy3 by an influence on the overall pattern of commensals and pathogens that stimulate the gut-associated lymphoid tissue. Similarly, an anthroposophic lifestyle may reduce the risk of atopy not as a consequence of wide exposure to measles, but by determining a different microbial stimulation of gut-associated lymphoid tissue at a critical period during infancy. *Data available from authors, on request.
*Paolo M Matricardi, Francesco Rosmini, Maria Rapicetta, Giovanni Gasbarrini, Tommaso Stroffolini, on the behalf of the San Marino Study Group *Laboratorio Immunologia ed Allergologia, Divisione Aerea Studi, Ricerche e Sperimentazioni, Aeroporto Pratica di Mare, 00040 Pomezia, Rome, Italy; Laboratori Epidemiologia e Biostatistica, Virologia, Istituto Superiore di Sanità, Rome; and Medicina Interna II, Università Cattolica S, Cuore, Rome 1
Alm J, Swartz J, Lilja G, Scheynius A, Pershagen G. Atopy in children of families with an anthroposophic lifestyle. Lancet 1999; 353: 1485–88. 2 Strachan DP. Lifestyle and atopy. Lancet 1999; 353: 1457–58. 3 Matricardi PM, Rosmini F, Ferrigno L, et al. Cross-sectional retrospective survey of prevalence of atopy among Italian military students with antibodies against hepatitis A virus. BMJ 1997; 314: 999–1003. 4 Stroffolini TM, Pretolani S, Miglio F, et al. Population-based survey of hepatitis A virus infection in the Republic of San Marino. Eur J Epidemiol 1997; 13: 687–89. 5 Grandolfo ME, Medda E, Novello F, et al. Seroepidemiological evaluation of 1989–91 mass vaccination campaigns against measles, in Italy. Epidemiol Infect 1998; 121: 645–52.
Transfusion with blood from people with HFE gene mutations Sir—Analyses for the C282Y and H63D mutations of the HFE gene in clinical1 and population2 samples allow the identification of healthy individuals who are at risk of hereditary haemochromatosis. Repeated phlebotomies are the only effective way to remove increased iron stores, and are required to prevent reaccumulation of iron in individuals at risk of haemochromatosis, thus affording them a normal life expectancy. 3 Prophylactic periodic venesections are recommended to carriers of mutations of the HFE gene, especially if they are homozygous. However, the units of blood thus obtained are thrown away, on the grounds that blood from individuals with genetic diseases is unsuitable for transfusion. In the Canary Islands, which has one of the highest rates of organ donors in the world,4 a chronic shortage of blood donations results in the frequent postponement of scheduled surgery. The blood units obtained from prophylactic venesections done only twice a year in the estimated 1 per 1000 population homozygous for the C282Y mutation of the HFE gene could boost by more than 5% the number of blood units in our region. We argue that blood from individuals with mutations of the HFE gene and no biochemical or haematological abnormalities (apart from the iron indices) could be safely used for blood transfusion, as must surely have happened in the past before the detection of these mutations. The present wasting of those blood resources is bad news for both the people with genetic haemochromatosis and for the general population. *Basilio J Anía, Carlos Rodríguez-Gallego Medicina Interna, Planta 10, Hospital Nuestra Señora del Pino, 35005, Las Palmas, Gran Canaria, Spain (e-mail: [email protected]) 1
The UK Haemochromatosis Consortium. A simple genetic test identifies 90% of UK patients with haemochromatosis. Gut 1997; 41: 841–44. 2 Burt MJ, George PM, Upton JD, et al. The significance of haemochromatosis gene mutations in the general population: implications for screening. Gut 1998; 43: 830–36. 3 Niederau C, Stremmel W, Strohmeyer GWW. Clinical spectrum and management of haemochromatosis. Baillieres Clin Haematol 1994; 7: 881–901. 4 Servicio Canario de Salud. Análisis del estado de salud de la población y de los recursos disponibles. Las Palmas, GC: Consejería de Sanidad y Consumo del Gobierno de Canarias, 1998: 188.
THE LANCET • Vol 354 • July 31, 1999
Atopy, hygiene, and anthroposophic lifestyle Sir—Johan Alm and colleagues (May 1, p 1485)1 report that atopy was rare in children from Swedish families who had an anthroposophic lifestyle. They speculate that failure of immunisation against measles, increased exposure to childhood infections, or dietary habits that affect the intestinal microflora may have contributed to the reduced risk of atopy. Their intriguing findings, however, are insufficient to test a specific aetiological hypothesis.2 Indeed, studies on a putative protective effect of childhood infections are still in their infancy and inconsistencies among initial observations must be remembered. 2 We reported a low prevalence of atopy among Italian military students exposed to the hepatitis A virus (HAV),3 which is a good marker of low hygienic standards. After that study, we tested the putative HAV-atopy inverse relation in another setting. We took advantage of a previous survey by Stroffolini and colleagues 4 on HAV seroprevalence in the adult general population of the Republic of San Marino, an independent state with 26 000 inhabitants (in 1998) that is completely surrounded by Northern Italy. Serum samples were collected during 1990–91 by a random-sample procedure (1527 men and women aged 肁20 years) and HAV antibodies were tested by E L I S A . 4 In 1509 (98·8%) of the serum sample, IgE against common airborne allergens were measured by a multi-radioallergosorbent assay as previously described; 3 a cut-off of logarithm of ratio units greater than 0·8 was chosen to define atopy. We found that atopy was strongly inversely related to HAV seropositivity: only 61 (6·23%) individuals were atopic among 979 HAV-seropositive participants, compared with 75 (14·15%) among 530 HAV-seronegative participants (p<0·001). The inverse association between HAV and atopy remained significant after adjustment for age and sex by multivariate analysis (odds ratio 0·59 [95% CI 0·38–0·92]). Stratification of data by year of birth showed an increasing trend of atopy among individuals born from 1960
430
onwards.* This trend is almost totally accounted for by individuals never exposed to HAV, because younger participants were less likely to be atopic if they had antibodies against HAV. We speculate that data obtained in San Marino support only one of Alm and colleagues’ suggestions. Indeed, since 1960 there has been an economic “boom” started in the Republic of San Marino, 4 w h e n lifestyle changes produced also a sharp improvement in hygienic standards. Conversely, mass immunisation programmes against measles started in this area (and all over Italy) only in the late 1980s so that measles epidemiology did not substantially change until early 1990s.5 Our data confirm an inverse association in Italy between exposure to HAV and atopy,3 and indicate that factor(s) specifically related to a faecal contamination of the environment, together with unhygienic food handling, may protect from atopy3 by an influence on the overall pattern of commensals and pathogens that stimulate the gut-associated lymphoid tissue. Similarly, an anthroposophic lifestyle may reduce the risk of atopy not as a consequence of wide exposure to measles, but by determining a different microbial stimulation of gut-associated lymphoid tissue at a critical period during infancy. *Data available from authors, on request.
*Paolo M Matricardi, Francesco Rosmini, Maria Rapicetta, Giovanni Gasbarrini, Tommaso Stroffolini, on the behalf of the San Marino Study Group *Laboratorio Immunologia ed Allergologia, Divisione Aerea Studi, Ricerche e Sperimentazioni, Aeroporto Pratica di Mare, 00040 Pomezia, Rome, Italy; Laboratori Epidemiologia e Biostatistica, Virologia, Istituto Superiore di Sanità, Rome; and Medicina Interna II, Università Cattolica S, Cuore, Rome 1
Alm J, Swartz J, Lilja G, Scheynius A, Pershagen G. Atopy in children of families with an anthroposophic lifestyle. Lancet 1999; 353: 1485–88. 2 Strachan DP. Lifestyle and atopy. Lancet 1999; 353: 1457–58. 3 Matricardi PM, Rosmini F, Ferrigno L, et al. Cross-sectional retrospective survey of prevalence of atopy among Italian military students with antibodies against hepatitis A virus. BMJ 1997; 314: 999–1003. 4 Stroffolini TM, Pretolani S, Miglio F, et al. Population-based survey of hepatitis A virus infection in the Republic of San Marino. Eur J Epidemiol 1997; 13: 687–89. 5 Grandolfo ME, Medda E, Novello F, et al. Seroepidemiological evaluation of 1989–91 mass vaccination campaigns against measles, in Italy. Epidemiol Infect 1998; 121: 645–52.
Transfusion with blood from people with HFE gene mutations Sir—Analyses for the C282Y and H63D mutations of the HFE gene in clinical1 and population2 samples allow the identification of healthy individuals who are at risk of hereditary haemochromatosis. Repeated phlebotomies are the only effective way to remove increased iron stores, and are required to prevent reaccumulation of iron in individuals at risk of haemochromatosis, thus affording them a normal life expectancy. 3 Prophylactic periodic venesections are recommended to carriers of mutations of the HFE gene, especially if they are homozygous. However, the units of blood thus obtained are thrown away, on the grounds that blood from individuals with genetic diseases is unsuitable for transfusion. In the Canary Islands, which has one of the highest rates of organ donors in the world,4 a chronic shortage of blood donations results in the frequent postponement of scheduled surgery. The blood units obtained from prophylactic venesections done only twice a year in the estimated 1 per 1000 population homozygous for the C282Y mutation of the HFE gene could boost by more than 5% the number of blood units in our region. We argue that blood from individuals with mutations of the HFE gene and no biochemical or haematological abnormalities (apart from the iron indices) could be safely used for blood transfusion, as must surely have happened in the past before the detection of these mutations. The present wasting of those blood resources is bad news for both the people with genetic haemochromatosis and for the general population. *Basilio J Anía, Carlos Rodríguez-Gallego Medicina Interna, Planta 10, Hospital Nuestra Señora del Pino, 35005, Las Palmas, Gran Canaria, Spain (e-mail: [email protected]) 1
The UK Haemochromatosis Consortium. A simple genetic test identifies 90% of UK patients with haemochromatosis. Gut 1997; 41: 841–44. 2 Burt MJ, George PM, Upton JD, et al. The significance of haemochromatosis gene mutations in the general population: implications for screening. Gut 1998; 43: 830–36. 3 Niederau C, Stremmel W, Strohmeyer GWW. Clinical spectrum and management of haemochromatosis. Baillieres Clin Haematol 1994; 7: 881–901. 4 Servicio Canario de Salud. Análisis del estado de salud de la población y de los recursos disponibles. Las Palmas, GC: Consejería de Sanidad y Consumo del Gobierno de Canarias, 1998: 188.
THE LANCET • Vol 354 • July 31, 1999