694
Handedness and autoantibodies SIR,-Reports have suggested that left-handed individuals have a shorter life span than right-handers.’Accidents,2 immune dysfunction,3 and brain damage,account for some, but not all, of the excess mortality among left-handers. Behan and Geschwind33 found an increased prevalence of certain autoimmune disorders among left-handed subjects. Circulating autoantibodies have been used as markers for an increased risk of autoimmune disease. As part of a continuing investigation examining autoimmune mechanisms in major mental illness, we have gathered data on handedness and autoantibodies in patients and healthy controls. Thus, we decided to examine the association (if any) between sinistrality and autoantibodies in healthy individuals. During the past 5 years, 346 healthy controls (mean age 32-1[SD 10 1] years) were recruited from the greater Pittsburgh area (table). They were screened to exclude current or past psychiatric illness, autoimmune diseases, and other illnesses. None were on long-term drugs. With standard serological techniques and commercial kits, sera were screened for autoantibodies to the following antigens: thyroid microsomes and thyroglobulin, mitochondria, smooth muscle, parietal cells, anti-nuclear antigen, and rheumatoid factor. The results were read by an immunologist who had no knowledge of the handedness data. Subjects were termed autoantibody positive if they had one or more circulating antibodies and autoantibody negative if they had none. Handedness was determined by asking about the writing hand, the foot used to kick a ball, and the eye used to look out of a monocular paper tube. Subjects were classed as right-handed or left-handed if all items were done with the right or left hand, respectively, and the remainder as mixed-handed. Mixed-handers were classified with left-handers for statistical
analyses. Handedness
compared against autoantibody status with the and Yates’ correction. Significantly more leftchi-square handers (37%) than right-handers (24%) had circulating autoantibodies (p 0-03, table). Strikingly more left-handed (41 %) than right-handed (17%) men had autoantibodies (p=0-007). More than twice as many left-handed (46%) than right-handed (20%) black individuals had autoantibodies (p=0-03). Curiously, among right-handers, significantly more women (28%) than men (17%) had autoantibodies (p = 0-04). Although this report suggests that there is an association between sinistrality and circulating autoantibodies even in young healthy subjects without diagnosable autoimmune diseases, it does not provide causal information. Two factors may account for this finding: evidence from animal studies suggests that left-sided but not right-sided cortical lesions cause impaired cellular immunity;5 and birth complications are more common in left-handers.4 Thus sinistrals may have an early left cerebral insult that results in both left-handedness and autoantibody production. We would emphasise a few points. As in previous reports, more men (25%) than women (20%) were sinistrals. More women (30%) than men (23%) had autoantibodies, which is similar to the prevalence of autoimmune diseases. Among left-handers, more men than women were antibody positive, whereas an opposite pattern emerged among right-handed individuals. Racial differences in autoantibody prevalence are puzzling, though immunological differences between blacks and whites have been reported. was
test
=
HANDEDNESS AND AUTOANTIBODY STATUSOF 346 HEALTHY SUBJECTS
Brain, Behaviour, and Immunity Centre,
ImmunoPsychiatry Program Schizophrenia Module, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
B. S. RABIN R. GANGULI
1. Halpern DF, Coren S. Do right-handers live longer? Nature 1988; 333: 213. 2. Coren S, Halpern, DF. Lelt-handedness: a marker for decreased survival fitness Psychol Bull 1991; 109: 90-106. 3. Behan PO, Geschwind N. Hemispheric lateraliry and immunity. In: Guillemin R, Cohn M, Melnechuk, eds. Neural modulation of immunity. New York. Raven Press, 1985: 73-80. 4. O’Callaghan MJ, Tudehope DI, Dugdale AE, Mohay H, Bums Y, Cook F. Handedness in children with birthweights below 1000 g. Lancet 1987; i. 1155. 5. Biziere K, Guillaumin JM, Degenne D, Bardos P, Renoux M. Lateralized neocortical modulation of the T-cell lineage. In: Guillemin R, Cohn M, Melnechuk T, eds. Neural modulation of immunity. New York: Raven Press, 1985: 81-94.
Anti-HIV cellular immunotherapy in AIDS SIR,-A phase 1 clinical trial was done in 1989-90 at the Saint Antoine Hospital, Paris, in AIDS patients who received every other 3 months (+15 days), by slow drip intravenous infusion, intramuscularly, and/or subcutaneously, inactivated, autologous, Epstein-Barr virus transformed B cells infected in vitro by recombinant vaccinia expressing the env, gag, and pol proteins of HIV-1Inactivation of infected cells was achieved by mitomycin C to block DNA synthesis, before fixation with paraformaldehyde and then incubation with hyperimmune antivaccine serum. Inactivation was assessed in vitro by co-cultivating samples of cell material with fresh transformed B cells. Cell immunotherapy was initiated in 1986 in African AIDS patients at the Cliniques Universitaires, Kinshasa, and it was given to a few AIDS patients in Paris in 1987. These patients were given inactivated autologous cells infected with HIV or with recombinant vaccinia expressing env gp 160 by the intravenous and, in some, by the intramuscular or subcutaneous routes. Several hundreds of intravenous infusions and over 60 injections were given and no
complications were seen. The trial at Saint Antoine Hospital was in two matched groups of fourteen pairs of patients with AID S or AID S-related complex and CD4 counts of 300 (SD 150)/nl. The treated group received the cells by infusion or injection and, again, no complications related to the cell injections occurred. However, in three of eight patients with terminal AIDS who were treated for humanitarian reasons (T4 cells 14, 33, and 43/ tl) a wide necrosis developed, extending from the site of subcutaneous/intramuscular injections and resulting in death.2 The Saint Antoine Hospital ethics committee was immediately informed of the first incident and this case was reported at the annual AIDS meeting of the US National Cancer Institute’s Tumour Cell Biology Laboratory in August, 1990. On the advice of the ethics committee we mentioned on the informed consent form the risk for necrosis. After the third fatal case in October, 1990, subcutaneous and intramuscular cell injections were stopped, not only in severely immunocompromised but also in all AIDS patients; the intravenous route was continued. At that time, we decided to publish these cases in an international AIDS journal. A letter was submitted to J AIDS in January, 1991, accepted in Feburary, and published in May.2 In the absence of any convincing cause for the necrosis, we suggested2 three hypotheses: live vaccinia virus still present after inactivation; Herpesvirw; hominis superinfection, as diagnosed by the pathologist and later confirmed in one case by syncytial cytopathic effect in culture; and toxic or allergic reactions. We thought the vaccinia hypothesis unlikely.2However, when we were informed in April, 1991, that vaccinia antigens had been found in keratinocytes of skin from one patient, we assumed that traces of vaccinia virus might have escaped inactivation and have given rise to necrosis in severely immunocompromised patients. This led us to 15, the administration of suspend immediately, as of vaccinia-infected cells to all patients, even though the intravenous injections had been innocuous all through the trials. We also asked J AIDS to include in our letter a reference to Guillaume et al/ who made the vaccinia diagnosis. All treated patients in the trial at Saint Antoine Hospital ran a normal life and were in regular work over the one-year follow-up.
April
AA+, autoantibody positive, AA-, autoantibody negative
K. N. ROY CHENGAPPA
J. COCHRAN
Handedness and autoantibodies SIR,-Reports have suggested that left-handed individuals have a shorter life span than right-handers.’Accidents,2 immune dysfunction,3 and brain damage,account for some, but not all, of the excess mortality among left-handers. Behan and Geschwind33 found an increased prevalence of certain autoimmune disorders among left-handed subjects. Circulating autoantibodies have been used as markers for an increased risk of autoimmune disease. As part of a continuing investigation examining autoimmune mechanisms in major mental illness, we have gathered data on handedness and autoantibodies in patients and healthy controls. Thus, we decided to examine the association (if any) between sinistrality and autoantibodies in healthy individuals. During the past 5 years, 346 healthy controls (mean age 32-1[SD 10 1] years) were recruited from the greater Pittsburgh area (table). They were screened to exclude current or past psychiatric illness, autoimmune diseases, and other illnesses. None were on long-term drugs. With standard serological techniques and commercial kits, sera were screened for autoantibodies to the following antigens: thyroid microsomes and thyroglobulin, mitochondria, smooth muscle, parietal cells, anti-nuclear antigen, and rheumatoid factor. The results were read by an immunologist who had no knowledge of the handedness data. Subjects were termed autoantibody positive if they had one or more circulating antibodies and autoantibody negative if they had none. Handedness was determined by asking about the writing hand, the foot used to kick a ball, and the eye used to look out of a monocular paper tube. Subjects were classed as right-handed or left-handed if all items were done with the right or left hand, respectively, and the remainder as mixed-handed. Mixed-handers were classified with left-handers for statistical
analyses. Handedness
compared against autoantibody status with the and Yates’ correction. Significantly more leftchi-square handers (37%) than right-handers (24%) had circulating autoantibodies (p 0-03, table). Strikingly more left-handed (41 %) than right-handed (17%) men had autoantibodies (p=0-007). More than twice as many left-handed (46%) than right-handed (20%) black individuals had autoantibodies (p=0-03). Curiously, among right-handers, significantly more women (28%) than men (17%) had autoantibodies (p = 0-04). Although this report suggests that there is an association between sinistrality and circulating autoantibodies even in young healthy subjects without diagnosable autoimmune diseases, it does not provide causal information. Two factors may account for this finding: evidence from animal studies suggests that left-sided but not right-sided cortical lesions cause impaired cellular immunity;5 and birth complications are more common in left-handers.4 Thus sinistrals may have an early left cerebral insult that results in both left-handedness and autoantibody production. We would emphasise a few points. As in previous reports, more men (25%) than women (20%) were sinistrals. More women (30%) than men (23%) had autoantibodies, which is similar to the prevalence of autoimmune diseases. Among left-handers, more men than women were antibody positive, whereas an opposite pattern emerged among right-handed individuals. Racial differences in autoantibody prevalence are puzzling, though immunological differences between blacks and whites have been reported. was
test
=
HANDEDNESS AND AUTOANTIBODY STATUSOF 346 HEALTHY SUBJECTS
Brain, Behaviour, and Immunity Centre,
ImmunoPsychiatry Program Schizophrenia Module, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
B. S. RABIN R. GANGULI
1. Halpern DF, Coren S. Do right-handers live longer? Nature 1988; 333: 213. 2. Coren S, Halpern, DF. Lelt-handedness: a marker for decreased survival fitness Psychol Bull 1991; 109: 90-106. 3. Behan PO, Geschwind N. Hemispheric lateraliry and immunity. In: Guillemin R, Cohn M, Melnechuk, eds. Neural modulation of immunity. New York. Raven Press, 1985: 73-80. 4. O’Callaghan MJ, Tudehope DI, Dugdale AE, Mohay H, Bums Y, Cook F. Handedness in children with birthweights below 1000 g. Lancet 1987; i. 1155. 5. Biziere K, Guillaumin JM, Degenne D, Bardos P, Renoux M. Lateralized neocortical modulation of the T-cell lineage. In: Guillemin R, Cohn M, Melnechuk T, eds. Neural modulation of immunity. New York: Raven Press, 1985: 81-94.
Anti-HIV cellular immunotherapy in AIDS SIR,-A phase 1 clinical trial was done in 1989-90 at the Saint Antoine Hospital, Paris, in AIDS patients who received every other 3 months (+15 days), by slow drip intravenous infusion, intramuscularly, and/or subcutaneously, inactivated, autologous, Epstein-Barr virus transformed B cells infected in vitro by recombinant vaccinia expressing the env, gag, and pol proteins of HIV-1Inactivation of infected cells was achieved by mitomycin C to block DNA synthesis, before fixation with paraformaldehyde and then incubation with hyperimmune antivaccine serum. Inactivation was assessed in vitro by co-cultivating samples of cell material with fresh transformed B cells. Cell immunotherapy was initiated in 1986 in African AIDS patients at the Cliniques Universitaires, Kinshasa, and it was given to a few AIDS patients in Paris in 1987. These patients were given inactivated autologous cells infected with HIV or with recombinant vaccinia expressing env gp 160 by the intravenous and, in some, by the intramuscular or subcutaneous routes. Several hundreds of intravenous infusions and over 60 injections were given and no
complications were seen. The trial at Saint Antoine Hospital was in two matched groups of fourteen pairs of patients with AID S or AID S-related complex and CD4 counts of 300 (SD 150)/nl. The treated group received the cells by infusion or injection and, again, no complications related to the cell injections occurred. However, in three of eight patients with terminal AIDS who were treated for humanitarian reasons (T4 cells 14, 33, and 43/ tl) a wide necrosis developed, extending from the site of subcutaneous/intramuscular injections and resulting in death.2 The Saint Antoine Hospital ethics committee was immediately informed of the first incident and this case was reported at the annual AIDS meeting of the US National Cancer Institute’s Tumour Cell Biology Laboratory in August, 1990. On the advice of the ethics committee we mentioned on the informed consent form the risk for necrosis. After the third fatal case in October, 1990, subcutaneous and intramuscular cell injections were stopped, not only in severely immunocompromised but also in all AIDS patients; the intravenous route was continued. At that time, we decided to publish these cases in an international AIDS journal. A letter was submitted to J AIDS in January, 1991, accepted in Feburary, and published in May.2 In the absence of any convincing cause for the necrosis, we suggested2 three hypotheses: live vaccinia virus still present after inactivation; Herpesvirw; hominis superinfection, as diagnosed by the pathologist and later confirmed in one case by syncytial cytopathic effect in culture; and toxic or allergic reactions. We thought the vaccinia hypothesis unlikely.2However, when we were informed in April, 1991, that vaccinia antigens had been found in keratinocytes of skin from one patient, we assumed that traces of vaccinia virus might have escaped inactivation and have given rise to necrosis in severely immunocompromised patients. This led us to 15, the administration of suspend immediately, as of vaccinia-infected cells to all patients, even though the intravenous injections had been innocuous all through the trials. We also asked J AIDS to include in our letter a reference to Guillaume et al/ who made the vaccinia diagnosis. All treated patients in the trial at Saint Antoine Hospital ran a normal life and were in regular work over the one-year follow-up.
April
AA+, autoantibody positive, AA-, autoantibody negative
K. N. ROY CHENGAPPA
J. COCHRAN
