- Email: [email protected]
ANTIPATERNAL LYMPHOCYTOTOXIC ANTIBODIES IN PREGNANCY
125 of IFN -&agr; detected in the patients prompts questions about the type and nature of virus replication and the site and timing of the infection. Lymphokines with or without damage to the microcirculation (as manifest by abnormal erythrocytes) may have their principal actions locally and systemic levels of IFN-&agr; would be expected to be low. This is especially so in a clinical relapse when primarily infected targets (eg, throat or gut) would not be contributing to the systemic IFN-’x response. Microbiology Department, Raiginore Hospital, Inverness IV2 3UJ, Virology Laboratory, Glasgow Royal Infirmary; and Virology Laboratory, Royal Hospital for Sick Children, Glasgow
Fig 2-10 min post-injection (anterior view).
1. Ho-Yen DO, Carrington D Alpha-interferon responses in cerebrospinal fluid of patients with suspected meningitis J Clin Pathol 1987, 40: 83-86. 2 Strauss S, Josato C, Armstrong C, et al Persisting illness and fatigue in adults with evidence of Epstein Barr virus infection Ann Intern Med 1985, 102: 7-16
Shows normal right testicle (open arrow) and swollen left testis surrounded by a dark halo of increased tracer uptake (closed arrow).
torsion from other causes of scrotal pain. In the diagnosis of testicular torsion it is very sensitive,3 and it is helpful in patients with possible inflammatory disease and in those who cannot be properly examined because of the severity of their signs and symptoms. If testicular perfusion is intact (ie, the scan is normal) laparotomy is unnecessary, and a review of 856 cases showed that exploration would be avoidable in 86% of patients.’ When the scan demonstrates a "cold" testicle, exploration is mandatory. Department of Nuclear Medicine, Charing Cross Hospital, London W6 8RF
DURVAL C. COSTA REGINALD F. JEWKES
Levy OM, Gillelman MC, Strashun AM, Cohen EL, Fine EJ. Diagnosis of acute testicular torsion using radionuclide scanning J Urol 1983; 129: 975-77. 2. Chen DCP, Holder LE, Melloul M Radionuclide scrotal imaging: Further experience with 210 new patients I anatomy, pathophysiology, and methods. J Nucl Med 1983, 24: 735-42. 3 Chen DCP, Holder LE, Melloul M Radionuclide scrotal imaging: Further experience with 210 new patients II: results and discussion J Nucl Med 1983; 24: 841-53. 4 Lutzker LG The fine points of scrotal scintigraphy. Sent Nucl Med 1982; 12: 387-93 1.
MYALGIC ENCEPHALOMYELITIS AND ALPHA-INTERFERON the discuss SIR,-Several of your correspondents pathophysiology of myalgic encephalomyelitis (ME) (also known as post viral fatigue syndrome and Royal Free disease). Dr Mukherjee and colleagues (Aug 8, p 328) show abnormal erythrocyte morphology and Professor Wakefield and Dr Lloyd (Oct 17, p 918) suggest the importance of lymphokines such as interferon. In patients being treated with alpha-interferon (IFN-T), Dr McDonald and colleagues (Nov 21, p 1175) find psychiatric symptoms similar to those in patients with ME. We have used a two-site immunoradiometric assay (’Sucrosep’, Boots-Celltech, Slough, UK) to measure IFN-&agr;.1 This assay
includes a monoclonal antibody to IFN-and is more sensitive and rapid than other biological methods. Blood was collected from 15 patients, who were within seven days of an exacerbation of ME and from 10 normal healthy controls. The mean (SD) serum IFN-a level in the patients was 0 76 (1-08) IU,ml, and in the controls it was 0 20 (0-21) IU ml. From a previous sensitivity study’ and other studies in our laboratories on a variety of biological specimens, a cut-off of 1-5 IU ml should be applied to these results. All the controls were below the cut-off but 3 patients had levels of 3 2, 28, and 2-4 IU ml, respectively. That interferon may be involved in the pathophysiology of ME is further supported by the finding of high levels of2,5-oligoadenylate synthetase, an interferon-induced enzyme, in 5 of 18 patients.2 Although this study2 did not find increased interferon levels, the interferon assay was not as sensitive and the clinical status of the patients was not considered. Our results, with a sensitive method and testing patients in relapse, confirm that systemically measured IFN-&agr;.levels are not particularly abnormal. However, the low levels
D. O. HO-YEN D. CARRINGTON ALISON A. ARMSTRONG
ANTIPATERNAL LYMPHOCYTOTOXIC ANTIBODIES IN PREGNANCY
SIR,-Dr Regan and Dr Braude, commenting (Nov 28, p 1280) et aP of lymphocyte infusions as spontaneous abortion, showed that antipaternal cytotoxic antibodies (APCA) were not necessary for the maintenance of a normal pregnancy nor were they a reliable indicator of successful pregnancy. We agree with their views on that study and indeed raised this issue over two years ago in your colurnns2 after the original study.; Regan and Braude show that APCA occur most frequently after the 28th week of a successful pregnancy and suggest that women who have recurrent spontaneous abortions have insufficiently long gestations to develop such antibodies. It may be further deduced that the lack of APCA in serum from women during early pregnancy, when most spontaneous abortions occur, makes it extremely unlikely that these cytotoxic antibodies play a protective role or indeed are even markers for other immune responses associated with successful pregnancy. We have shown that non-cytotoxic antibodies, detectable both by a rosette inhibition assay’ and a cellular-based ELISA,’ occur in sera from women during the first trimester of a normal pregnancy but not from women who have recurrent spontaneous abortions. Such antibodies have also been detected after blood transfusion in patients awaiting renal transplantation’,’ and may represent one mechanism by which transfusions improve allograft survival. There is some evidence, therefore, that they play a protective role. It may thus be of value to search for both cytotoxic and non-cytotoxic antibodies in serum from women before and during normal pregnancy and in those receiving lymphocyte infusions as treatment for recurrent spontaneous abortions. Only by doing this will antibodies associated with or predictive of successful pregnancy be identified. on
the
study by Mowbray
treatment
for
recurrent
Department of Medicine & Therapeutics Polwarth Building, Foresterhill, Aberdeen AB9 2ZD 1.
ALISON M. MACLEOD GRAEME R. D. CATTO
Mowbray JF, Underwood JL, Michel M, Forbes PB, Beard RW Immunisation with paternal lymphocytes in women with recurrent miscarriage Lancet 1987, ii: 679-80
2 MacLeod
3.
4. 5.
6. 7.
8.
AM, Power DA, Catto GRD. Pregnancy lymphocytes Lancet 1985; ii: 508. Mowbray JF, Gibbins C, Lidell H, Reginald PW,
after
treatment
with
paternal
Underwood JL, Beard RW. Controlled trial of treatment of recurrent spontaneous abortion with paternal cells. Lancet 1985, i: 941-43 Power DA, Catto GRD, Mason RJ, et al The fetus as an allograft Evidence for protective antibodies to HLA-linked paternal antigens Lancet 1983, ii 701-04. Cunningham C, Power DA, Innes A, Lind T, Catto GRD. Maternal alloantibody responses during early pregnancy detected by a cellular enzyme-linked immunospecific assay. Hum Immunol 1987, 19: 7-16 MacLeod AM, Power DA, Mason RJ, et al The transfusion effect in renal tramplantation: a possible mechanism of action. Lancet 1982, ii: 468-70 MacLeod AM, Hillis AN, Mather A, Bone JM, Catto GRD Effect of cyclosporin, previous third party transfusion, and pregnancy on sensitisation after donorspecific transfusion before renal transplantation Lancet 1987; i: 416-18. Innes A, Hillis A, MacLeod AM, Cunningham C, Power DA, Catto GRD. Donor specific blood transfusion induces antibodies detectable by cellular enzyme-linked immunospecific assay Abstr Xth Int Congr Nephrol organised by the International Society of Nephrology, held in London on July 26-31, 1987: 599
Fig 2-10 min post-injection (anterior view).
1. Ho-Yen DO, Carrington D Alpha-interferon responses in cerebrospinal fluid of patients with suspected meningitis J Clin Pathol 1987, 40: 83-86. 2 Strauss S, Josato C, Armstrong C, et al Persisting illness and fatigue in adults with evidence of Epstein Barr virus infection Ann Intern Med 1985, 102: 7-16
Shows normal right testicle (open arrow) and swollen left testis surrounded by a dark halo of increased tracer uptake (closed arrow).
torsion from other causes of scrotal pain. In the diagnosis of testicular torsion it is very sensitive,3 and it is helpful in patients with possible inflammatory disease and in those who cannot be properly examined because of the severity of their signs and symptoms. If testicular perfusion is intact (ie, the scan is normal) laparotomy is unnecessary, and a review of 856 cases showed that exploration would be avoidable in 86% of patients.’ When the scan demonstrates a "cold" testicle, exploration is mandatory. Department of Nuclear Medicine, Charing Cross Hospital, London W6 8RF
DURVAL C. COSTA REGINALD F. JEWKES
Levy OM, Gillelman MC, Strashun AM, Cohen EL, Fine EJ. Diagnosis of acute testicular torsion using radionuclide scanning J Urol 1983; 129: 975-77. 2. Chen DCP, Holder LE, Melloul M Radionuclide scrotal imaging: Further experience with 210 new patients I anatomy, pathophysiology, and methods. J Nucl Med 1983, 24: 735-42. 3 Chen DCP, Holder LE, Melloul M Radionuclide scrotal imaging: Further experience with 210 new patients II: results and discussion J Nucl Med 1983; 24: 841-53. 4 Lutzker LG The fine points of scrotal scintigraphy. Sent Nucl Med 1982; 12: 387-93 1.
MYALGIC ENCEPHALOMYELITIS AND ALPHA-INTERFERON the discuss SIR,-Several of your correspondents pathophysiology of myalgic encephalomyelitis (ME) (also known as post viral fatigue syndrome and Royal Free disease). Dr Mukherjee and colleagues (Aug 8, p 328) show abnormal erythrocyte morphology and Professor Wakefield and Dr Lloyd (Oct 17, p 918) suggest the importance of lymphokines such as interferon. In patients being treated with alpha-interferon (IFN-T), Dr McDonald and colleagues (Nov 21, p 1175) find psychiatric symptoms similar to those in patients with ME. We have used a two-site immunoradiometric assay (’Sucrosep’, Boots-Celltech, Slough, UK) to measure IFN-&agr;.1 This assay
includes a monoclonal antibody to IFN-and is more sensitive and rapid than other biological methods. Blood was collected from 15 patients, who were within seven days of an exacerbation of ME and from 10 normal healthy controls. The mean (SD) serum IFN-a level in the patients was 0 76 (1-08) IU,ml, and in the controls it was 0 20 (0-21) IU ml. From a previous sensitivity study’ and other studies in our laboratories on a variety of biological specimens, a cut-off of 1-5 IU ml should be applied to these results. All the controls were below the cut-off but 3 patients had levels of 3 2, 28, and 2-4 IU ml, respectively. That interferon may be involved in the pathophysiology of ME is further supported by the finding of high levels of2,5-oligoadenylate synthetase, an interferon-induced enzyme, in 5 of 18 patients.2 Although this study2 did not find increased interferon levels, the interferon assay was not as sensitive and the clinical status of the patients was not considered. Our results, with a sensitive method and testing patients in relapse, confirm that systemically measured IFN-&agr;.levels are not particularly abnormal. However, the low levels
D. O. HO-YEN D. CARRINGTON ALISON A. ARMSTRONG
ANTIPATERNAL LYMPHOCYTOTOXIC ANTIBODIES IN PREGNANCY
SIR,-Dr Regan and Dr Braude, commenting (Nov 28, p 1280) et aP of lymphocyte infusions as spontaneous abortion, showed that antipaternal cytotoxic antibodies (APCA) were not necessary for the maintenance of a normal pregnancy nor were they a reliable indicator of successful pregnancy. We agree with their views on that study and indeed raised this issue over two years ago in your colurnns2 after the original study.; Regan and Braude show that APCA occur most frequently after the 28th week of a successful pregnancy and suggest that women who have recurrent spontaneous abortions have insufficiently long gestations to develop such antibodies. It may be further deduced that the lack of APCA in serum from women during early pregnancy, when most spontaneous abortions occur, makes it extremely unlikely that these cytotoxic antibodies play a protective role or indeed are even markers for other immune responses associated with successful pregnancy. We have shown that non-cytotoxic antibodies, detectable both by a rosette inhibition assay’ and a cellular-based ELISA,’ occur in sera from women during the first trimester of a normal pregnancy but not from women who have recurrent spontaneous abortions. Such antibodies have also been detected after blood transfusion in patients awaiting renal transplantation’,’ and may represent one mechanism by which transfusions improve allograft survival. There is some evidence, therefore, that they play a protective role. It may thus be of value to search for both cytotoxic and non-cytotoxic antibodies in serum from women before and during normal pregnancy and in those receiving lymphocyte infusions as treatment for recurrent spontaneous abortions. Only by doing this will antibodies associated with or predictive of successful pregnancy be identified. on
the
study by Mowbray
treatment
for
recurrent
Department of Medicine & Therapeutics Polwarth Building, Foresterhill, Aberdeen AB9 2ZD 1.
ALISON M. MACLEOD GRAEME R. D. CATTO
Mowbray JF, Underwood JL, Michel M, Forbes PB, Beard RW Immunisation with paternal lymphocytes in women with recurrent miscarriage Lancet 1987, ii: 679-80
2 MacLeod
3.
4. 5.
6. 7.
8.
AM, Power DA, Catto GRD. Pregnancy lymphocytes Lancet 1985; ii: 508. Mowbray JF, Gibbins C, Lidell H, Reginald PW,
after
treatment
with
paternal
Underwood JL, Beard RW. Controlled trial of treatment of recurrent spontaneous abortion with paternal cells. Lancet 1985, i: 941-43 Power DA, Catto GRD, Mason RJ, et al The fetus as an allograft Evidence for protective antibodies to HLA-linked paternal antigens Lancet 1983, ii 701-04. Cunningham C, Power DA, Innes A, Lind T, Catto GRD. Maternal alloantibody responses during early pregnancy detected by a cellular enzyme-linked immunospecific assay. Hum Immunol 1987, 19: 7-16 MacLeod AM, Power DA, Mason RJ, et al The transfusion effect in renal tramplantation: a possible mechanism of action. Lancet 1982, ii: 468-70 MacLeod AM, Hillis AN, Mather A, Bone JM, Catto GRD Effect of cyclosporin, previous third party transfusion, and pregnancy on sensitisation after donorspecific transfusion before renal transplantation Lancet 1987; i: 416-18. Innes A, Hillis A, MacLeod AM, Cunningham C, Power DA, Catto GRD. Donor specific blood transfusion induces antibodies detectable by cellular enzyme-linked immunospecific assay Abstr Xth Int Congr Nephrol organised by the International Society of Nephrology, held in London on July 26-31, 1987: 599