736
smokers, and who have delayed resolution of acute pneumonia irrespective of the causative organism, particularly if they have received tetracycline, a drug said to be useful in the treatment of legionnaires’ disease? This is our policy. I wonder how many cases of carcinoma of bronchus at a potentially "curable" stage would be missed if patients fitting the above are
description were not investigated by bronchoscopy. Waller Cardio-pulmonary St Mary’s Hospital, London W2 1NY
Unit,
C. R. NYMAN
ADVERSE RESPONSE TO ALPHADOLONE/ALPHAXALONE: POSSIBLE ROLE OF IgD
SiR,—Anaphylactoid reactions to the steroid intravenous hypnotic drug ’Althesin’ (alphadolone+alphaxalone) seem to2 be predominantly mediated by complement C3 activation. 1 a small proportion of these reactions do appear be immune mediated.13 IgE seems to be involved in some reactions but in a small group the anaphylactoid reaction follows readministration of althesin 1-4 weeks after the first induction. A conventional antibody response could occur over such an interval, but this is unlikely with a steroid drug, and we have considered the possibility of short-term "memory" involving lymphocyte receptors. This view is strengthened by a
Nevertheless, to
IgD
AND
IgE
LEVELS IN FAMILIES OF TWO PATIENTS
Hours after Induction in plasma IgE and reaction to althesin.
Changes
IgD
in
patient
with
anaphylactoid
WITfI
ALTHESIN REACTIONS
We re-examined plasma from six patients who had shown clear evidence of complement C3 conversion as the mechanism of response. None of the patients had had a previous exposure to althesin and therefore a specific immune-mediated mechanism was unlikely. Plasma IgD and IgE values were normal. Of a further six patients who had received althesin on a previous occasion more than 2 months before the adverse reaction, three showed evidence of antibody-mediated response but they all had plasma-IgE levels well below the median far the normal population. IgD values ranged from 0 to 30 I.u./ml. However, of three patients previously exposed to althesin no more than 3 weeks previously, two had very high IgD levels. One of these patients and the third reactant also were probably atopic (IgE>200 i.u./ml). The families of the two reactors with high IgD have been investigated (table). Family T shows the inheritance of high IgD levels. Family W, where the high-IgE trait is apparently inherited from the father, indicates that the IgD level may be expressed by a recessive gene. In such cases the IgD could be expressed by raised cell-bound levels, since the correlation between high plasma-IgE and cell-bound IgE may not hold for IgD. We have seen apparent IgD involvement after adverse response even in patients with normal IgD values (figure). The rising IgD level suggests displacement of cell-bound molecules.’ The concomitant fall in plasma-IgE is real and elsewhere we suggest reasons for this.8 There thus seems to be some evidence for involvement of IgD in certain types of adverse reaction to althesin. Certainly, close proximity of exposures to this drug appears to be a factor predisposing to adverse response.8 We have not seen an analogous situation with the barbiturate hypnotics, and it may be that these responses are more pronounced with althesin due to the use of ’Cremophor EL’ in the formulation. This detergelit may present drugs more avidly to cellular receptors such as IgE and IgD. ’
*Values exceeding age-corrected 95th centile. Reference values (normal adult population) are for IgD, median 15 and 95th centile 80, and for IgE, median 83 and 95th centile 200.
report of a similar reaction to althesin in the Miniature pig.4. In this animal a second exposure within 2 weeks gives rise to a marked anaphylactoid reaction. This reaction is greatly decreased or lost when the second exposure takes place less than 1 week or more than 2 weeks after the sensitising exposure. We wondered whether IgD could be involved in such memory reactions. Others have suggested that IgD may play an important role in the expression of immune responses, perhaps in the control of cell-mediated immunity.s IgD is present on a high proportion of circulating B lymphocytes in man.6 Plasma-IgD can be measured by single radial immunodiffusion in agar with commercial standards and antiserum (Hoechst). IgE is estimated by solid-phase radioimmunoassay
(Pharmacia). Watkins, J., Ward, A. M., Appleyard, T. N. Br. med. J. 1977, ii, 1084. Watkins, J., Udnoon, S., Appleyard, T. N., Thornton, J. A. Br. J. Anæsth. 1976, 48, 457. 3. Watkins, J., Clark, A., Appleyard, T. N., Padfield, A. ibid. 1976, 48, 881. 4. Glen, J. B., Davies, G. E., Thomson, D. S., Scarth, S. C., Thompson, A. V. in Adverse Response to Intravenous Drugs (edited by J. Watkins, and 1. 2.
A. M.
5. 6.
Ward). London (in the press).
Row, D. S., Hug, K., Forni, L., Pernis, B.J. exp. Med. 1973, 138, 965. Bargellesi, A., Corte, G., Cosulich, E., Ferrarini, M., Sitia, R., Viale, G. Ricerca Clin. Lab.
1978, 8 suppl. 1, p. 195.
Department of Immunology, Hallamshire Hospital Medical School, Sheffield S10 2RX
7.
Bourgois, A., Abney,
E. R., Parkhouse, R. M. E.
J. WATKINS REBECCA ALLEN A. MILFORD WARD
Eur. J.
Immun.
1977, 7,
210. Intravenous
8. Watkins, J., Udnoon, S., Taussig, P. E. in Adverse response Drugs (edited by J. Watkins and A. M. Ward). London (in the press). to
smokers, and who have delayed resolution of acute pneumonia irrespective of the causative organism, particularly if they have received tetracycline, a drug said to be useful in the treatment of legionnaires’ disease? This is our policy. I wonder how many cases of carcinoma of bronchus at a potentially "curable" stage would be missed if patients fitting the above are
description were not investigated by bronchoscopy. Waller Cardio-pulmonary St Mary’s Hospital, London W2 1NY
Unit,
C. R. NYMAN
ADVERSE RESPONSE TO ALPHADOLONE/ALPHAXALONE: POSSIBLE ROLE OF IgD
SiR,—Anaphylactoid reactions to the steroid intravenous hypnotic drug ’Althesin’ (alphadolone+alphaxalone) seem to2 be predominantly mediated by complement C3 activation. 1 a small proportion of these reactions do appear be immune mediated.13 IgE seems to be involved in some reactions but in a small group the anaphylactoid reaction follows readministration of althesin 1-4 weeks after the first induction. A conventional antibody response could occur over such an interval, but this is unlikely with a steroid drug, and we have considered the possibility of short-term "memory" involving lymphocyte receptors. This view is strengthened by a
Nevertheless, to
IgD
AND
IgE
LEVELS IN FAMILIES OF TWO PATIENTS
Hours after Induction in plasma IgE and reaction to althesin.
Changes
IgD
in
patient
with
anaphylactoid
WITfI
ALTHESIN REACTIONS
We re-examined plasma from six patients who had shown clear evidence of complement C3 conversion as the mechanism of response. None of the patients had had a previous exposure to althesin and therefore a specific immune-mediated mechanism was unlikely. Plasma IgD and IgE values were normal. Of a further six patients who had received althesin on a previous occasion more than 2 months before the adverse reaction, three showed evidence of antibody-mediated response but they all had plasma-IgE levels well below the median far the normal population. IgD values ranged from 0 to 30 I.u./ml. However, of three patients previously exposed to althesin no more than 3 weeks previously, two had very high IgD levels. One of these patients and the third reactant also were probably atopic (IgE>200 i.u./ml). The families of the two reactors with high IgD have been investigated (table). Family T shows the inheritance of high IgD levels. Family W, where the high-IgE trait is apparently inherited from the father, indicates that the IgD level may be expressed by a recessive gene. In such cases the IgD could be expressed by raised cell-bound levels, since the correlation between high plasma-IgE and cell-bound IgE may not hold for IgD. We have seen apparent IgD involvement after adverse response even in patients with normal IgD values (figure). The rising IgD level suggests displacement of cell-bound molecules.’ The concomitant fall in plasma-IgE is real and elsewhere we suggest reasons for this.8 There thus seems to be some evidence for involvement of IgD in certain types of adverse reaction to althesin. Certainly, close proximity of exposures to this drug appears to be a factor predisposing to adverse response.8 We have not seen an analogous situation with the barbiturate hypnotics, and it may be that these responses are more pronounced with althesin due to the use of ’Cremophor EL’ in the formulation. This detergelit may present drugs more avidly to cellular receptors such as IgE and IgD. ’
*Values exceeding age-corrected 95th centile. Reference values (normal adult population) are for IgD, median 15 and 95th centile 80, and for IgE, median 83 and 95th centile 200.
report of a similar reaction to althesin in the Miniature pig.4. In this animal a second exposure within 2 weeks gives rise to a marked anaphylactoid reaction. This reaction is greatly decreased or lost when the second exposure takes place less than 1 week or more than 2 weeks after the sensitising exposure. We wondered whether IgD could be involved in such memory reactions. Others have suggested that IgD may play an important role in the expression of immune responses, perhaps in the control of cell-mediated immunity.s IgD is present on a high proportion of circulating B lymphocytes in man.6 Plasma-IgD can be measured by single radial immunodiffusion in agar with commercial standards and antiserum (Hoechst). IgE is estimated by solid-phase radioimmunoassay
(Pharmacia). Watkins, J., Ward, A. M., Appleyard, T. N. Br. med. J. 1977, ii, 1084. Watkins, J., Udnoon, S., Appleyard, T. N., Thornton, J. A. Br. J. Anæsth. 1976, 48, 457. 3. Watkins, J., Clark, A., Appleyard, T. N., Padfield, A. ibid. 1976, 48, 881. 4. Glen, J. B., Davies, G. E., Thomson, D. S., Scarth, S. C., Thompson, A. V. in Adverse Response to Intravenous Drugs (edited by J. Watkins, and 1. 2.
A. M.
5. 6.
Ward). London (in the press).
Row, D. S., Hug, K., Forni, L., Pernis, B.J. exp. Med. 1973, 138, 965. Bargellesi, A., Corte, G., Cosulich, E., Ferrarini, M., Sitia, R., Viale, G. Ricerca Clin. Lab.
1978, 8 suppl. 1, p. 195.
Department of Immunology, Hallamshire Hospital Medical School, Sheffield S10 2RX
7.
Bourgois, A., Abney,
E. R., Parkhouse, R. M. E.
J. WATKINS REBECCA ALLEN A. MILFORD WARD
Eur. J.
Immun.
1977, 7,
210. Intravenous
8. Watkins, J., Udnoon, S., Taussig, P. E. in Adverse response Drugs (edited by J. Watkins and A. M. Ward). London (in the press). to
