918 PHAGOCYTE FUNCTION IN SYSTEMIC LUPUS ERYTHEMATOSUS
SiR,—The hypothesis defective (S.L.E.) is
discard
D.N.A.
of Gabrielsen1 in systemic lupus some evidence of
concerning a erythematosus dysfunction of
supported by phagocytosis in S.L.E.2 This dysfunction has been confirmed by us in 8 out of 9 patients by polymorphonuclearleucocyte (P.M.N.) incubation with Klebsiella in normal human serum (a partial modification of Mandell and Hook’s technique 3) (66 _ 16-73% ingested Klebsiella v. 97,7-3::. 1-1% in normal controls). Impaired reduction of nitroblue tetrazolium (N.B.T.) by 4 and by resting -1,6or latex-stimulated blood marrow cells P.M.N.2 has been described in s.L.E., even during bacterial infections. 6-8 In contrast
normal results obtained with maximum P.M.N.,5,8 we observed a consistent impairment of N.B.T. reduction, unrelated to plasma factors, treatment, or activity of the disease, in s.L.E. P.M.N. stimulated with submaximum doses of Escherichia coli endotoxin or 0,8 [J. latex particles by a modification of Park’s tech-
stimulation of
to
We have noted impairment of N.B.T. reduction in 4 out of 7 members of a family, all of whom have S.L.E. or other autoimmune disorders. We are now investigating the possible relationship of P.M.N. dysfunction with the emergence of lupus disease in NZB/NZW hybrids. We suggest that a complex deficiency of the scavenger function of the reticuloendothelial system, known to be active, by disposal of altered proteins, in protecting against autoimmune disorders, could be associated with immune defects in the pathogenesis of S.L.E.
C. BESANA A. LAZZARIN F. CAPSONI F. CAREDDA M. MORONI.
Istituto di Clinica Medica IV, 35 via Francesco Sforza, 20122 Milan, Italy.
S.L.E.
nique9 (see accompanying table). The absence of any link between the severity of the phagocytic defect and the clinical course of the disease seems to rule out the importance of an inhibitory effect by immune complexes on phagocytosis 10 and N.B.T. reduction,11 or by other plasma factors. Inhibition of N.B.T. reduction has been recorded in acute virus diseases, 1but its occurrence in slow virus disease and the role of virus in human S.L.E. are so far in doubt. In support of the pathogenetic significance in S.L.E. of a pre-existing phagocyte dysfunction, we recall: the lupuslike syndromes in genetically complement-deficient patients 13-15 and in mothers of children with chronic granulomatous diseaseor other congenital granulocyte dysfunctions ; and the association of IgA deficiency, which has been described in S.L.E.," with phagocyte dysfunction
syndromes. 18
CYSTIC FIBROSIS: DETECTION OF HETEROZYGOTES
SIR,-Samuels and Elliott’ have described a new technique for detecting cystic fibrosis (c.F.) and the heterozygote for c.F. This involves measurement of the inhibition by prostaglandin E, (p.G.E1) of A.D.p.-induced platelet aggregation. p.G.Et was said to inhibit A.D.p.-induced aggregation less in c.F. patients and known heterozygotes than in healthy controls. They reported that they could detect all 25 c.F. patients and 95% of the 40 known heterozygotes tested. One implication of their report was that there were no false-positive results in the controls. We have tested this technique in detail on a smaller number of patients (4 with c.F., 4 parents of the c.F. children, and 4 controls). Blood was collected from 1 patient with c.F., 1 parent, and 1 control on each of four occasions. No subject had had aspirin in the preceding seven days. The preparation of blood for tests of aggregation, and the methodology, have been
described
previously.2
on platelet-rich plasma with a plateletof 300 OOG-400,000/ji-I were run in parallel using a dual-channel Payton aggregometer and SP-HSV chart recorder. All patients and controls were tested first with 2 and 8 lamol A.D.P. (final concentration). The tests were then repeated, adding P.G.E, (1 uLg/ml final concentration) ten seconds before adding A.D.P. In addition, the release of 14C-serotonin in response to P..E, + 8 ymol A.D.P. was estimated. P.G.E, inhibited aggregation equally in all cases and there was no release of 14C-serotonin. Although the number of samples tested in our study is small, results suggest that this technique is not likely to be successful B in detection of heterozygotes for C.F. P.G.E,, batch U-10136, was kindly provided by Upjohn Company, Kalamazoo, Michigan, U.S.A.
Tests
performed
count 1. 2.
3. 4.
5. 6. 7. 8. 9. 10.
11. 12. 13.
14. 15. 16. 17.
Gabrielsen, A. E. Lancet, 1974, ii, 1116. Douwes, F. R., Schött, D. 2nd International Symposium on Metabolism and Membrane Permeability of Erythrocytes, Thrombocytes and Leucocytes. Vienna, 1972. Mandell, G. L., Hook, E. W. Am J. Med. 1969, 47, 473. Lapes, M., Desai, A., Rosenzweig, M., Smalley, R., Barbieri, B. New Engl. J. Med. 1973, 289, 1255. Tratt, G. E., Myers, A., Moellering, R. C., Weinberg, A. N., Bloch, K. J. Arthr. Rheum. 1970, 13, 353. Douwes, F. R. New Engl. J. Med. 1972, 287, 822. Douwes, F. R. ibid. p. 1150. Douwes, F. R. J. Lab. clin. Med. 1973, 82, 513. Park, B. H., Good, R. A. Lancet, 1970, ii, 616. Turner, R. A., Schumacher, H. R., Myers, A. R. J. clin. Invest. 1973, 52, 1632. Segal, A. W. Lancet, 1974, ii, 1248. Freeman, R., King, B., Kite, P. J. clin. Path. 1973, 26, 57. Moncada, B., Day, N. K., Good, R. A., Windhorst, D. B. New Engl. J. Med. 1972, 286, 689. Day, N. K., Geiger, H., McLean, R., Michael, A., Good, R. A. J. clin. Invest. 1973, 52, 1601. Hauptmann, G., Grosshans, E., Heid, E. Boll. Ist. Sieroter. Milan, 1974, 53, 228. Schaller, J. Arthr. Rheum. 1971, 14, 411. Amman, A. J., Hong, R. Medicine, 1971, 50, 223.
18. Fudenberg, H. H. in Phagocytic Mechanisms in Health and Disease (edited by R. C. Williams and H. H. Fudenberg); Stuttgart, 1972.
Departments of Gastroenterology Hæmatology, Royal Children’s Hospital,
and
G. L. BARNES H. EKERT S.V. DOWLING
Parkville, Melbourne, Australia 3052.
1. Samuels, C. E., Elliott, R. B. Lancet, Sept. 2. Ekert, H., Sheers, M. J. thorac. cardiovasc.
PERCENTAGE OF N.B.T.-REDUCING CELLS IN S.L.E. PATIENTS AND
27, 1975, p. 607 Surg. 1974, 67, 184.
NORMAL CONTROLS
SiR,—The hypothesis defective (S.L.E.) is
discard
D.N.A.
of Gabrielsen1 in systemic lupus some evidence of
concerning a erythematosus dysfunction of
supported by phagocytosis in S.L.E.2 This dysfunction has been confirmed by us in 8 out of 9 patients by polymorphonuclearleucocyte (P.M.N.) incubation with Klebsiella in normal human serum (a partial modification of Mandell and Hook’s technique 3) (66 _ 16-73% ingested Klebsiella v. 97,7-3::. 1-1% in normal controls). Impaired reduction of nitroblue tetrazolium (N.B.T.) by 4 and by resting -1,6or latex-stimulated blood marrow cells P.M.N.2 has been described in s.L.E., even during bacterial infections. 6-8 In contrast
normal results obtained with maximum P.M.N.,5,8 we observed a consistent impairment of N.B.T. reduction, unrelated to plasma factors, treatment, or activity of the disease, in s.L.E. P.M.N. stimulated with submaximum doses of Escherichia coli endotoxin or 0,8 [J. latex particles by a modification of Park’s tech-
stimulation of
to
We have noted impairment of N.B.T. reduction in 4 out of 7 members of a family, all of whom have S.L.E. or other autoimmune disorders. We are now investigating the possible relationship of P.M.N. dysfunction with the emergence of lupus disease in NZB/NZW hybrids. We suggest that a complex deficiency of the scavenger function of the reticuloendothelial system, known to be active, by disposal of altered proteins, in protecting against autoimmune disorders, could be associated with immune defects in the pathogenesis of S.L.E.
C. BESANA A. LAZZARIN F. CAPSONI F. CAREDDA M. MORONI.
Istituto di Clinica Medica IV, 35 via Francesco Sforza, 20122 Milan, Italy.
S.L.E.
nique9 (see accompanying table). The absence of any link between the severity of the phagocytic defect and the clinical course of the disease seems to rule out the importance of an inhibitory effect by immune complexes on phagocytosis 10 and N.B.T. reduction,11 or by other plasma factors. Inhibition of N.B.T. reduction has been recorded in acute virus diseases, 1but its occurrence in slow virus disease and the role of virus in human S.L.E. are so far in doubt. In support of the pathogenetic significance in S.L.E. of a pre-existing phagocyte dysfunction, we recall: the lupuslike syndromes in genetically complement-deficient patients 13-15 and in mothers of children with chronic granulomatous diseaseor other congenital granulocyte dysfunctions ; and the association of IgA deficiency, which has been described in S.L.E.," with phagocyte dysfunction
syndromes. 18
CYSTIC FIBROSIS: DETECTION OF HETEROZYGOTES
SIR,-Samuels and Elliott’ have described a new technique for detecting cystic fibrosis (c.F.) and the heterozygote for c.F. This involves measurement of the inhibition by prostaglandin E, (p.G.E1) of A.D.p.-induced platelet aggregation. p.G.Et was said to inhibit A.D.p.-induced aggregation less in c.F. patients and known heterozygotes than in healthy controls. They reported that they could detect all 25 c.F. patients and 95% of the 40 known heterozygotes tested. One implication of their report was that there were no false-positive results in the controls. We have tested this technique in detail on a smaller number of patients (4 with c.F., 4 parents of the c.F. children, and 4 controls). Blood was collected from 1 patient with c.F., 1 parent, and 1 control on each of four occasions. No subject had had aspirin in the preceding seven days. The preparation of blood for tests of aggregation, and the methodology, have been
described
previously.2
on platelet-rich plasma with a plateletof 300 OOG-400,000/ji-I were run in parallel using a dual-channel Payton aggregometer and SP-HSV chart recorder. All patients and controls were tested first with 2 and 8 lamol A.D.P. (final concentration). The tests were then repeated, adding P.G.E, (1 uLg/ml final concentration) ten seconds before adding A.D.P. In addition, the release of 14C-serotonin in response to P..E, + 8 ymol A.D.P. was estimated. P.G.E, inhibited aggregation equally in all cases and there was no release of 14C-serotonin. Although the number of samples tested in our study is small, results suggest that this technique is not likely to be successful B in detection of heterozygotes for C.F. P.G.E,, batch U-10136, was kindly provided by Upjohn Company, Kalamazoo, Michigan, U.S.A.
Tests
performed
count 1. 2.
3. 4.
5. 6. 7. 8. 9. 10.
11. 12. 13.
14. 15. 16. 17.
Gabrielsen, A. E. Lancet, 1974, ii, 1116. Douwes, F. R., Schött, D. 2nd International Symposium on Metabolism and Membrane Permeability of Erythrocytes, Thrombocytes and Leucocytes. Vienna, 1972. Mandell, G. L., Hook, E. W. Am J. Med. 1969, 47, 473. Lapes, M., Desai, A., Rosenzweig, M., Smalley, R., Barbieri, B. New Engl. J. Med. 1973, 289, 1255. Tratt, G. E., Myers, A., Moellering, R. C., Weinberg, A. N., Bloch, K. J. Arthr. Rheum. 1970, 13, 353. Douwes, F. R. New Engl. J. Med. 1972, 287, 822. Douwes, F. R. ibid. p. 1150. Douwes, F. R. J. Lab. clin. Med. 1973, 82, 513. Park, B. H., Good, R. A. Lancet, 1970, ii, 616. Turner, R. A., Schumacher, H. R., Myers, A. R. J. clin. Invest. 1973, 52, 1632. Segal, A. W. Lancet, 1974, ii, 1248. Freeman, R., King, B., Kite, P. J. clin. Path. 1973, 26, 57. Moncada, B., Day, N. K., Good, R. A., Windhorst, D. B. New Engl. J. Med. 1972, 286, 689. Day, N. K., Geiger, H., McLean, R., Michael, A., Good, R. A. J. clin. Invest. 1973, 52, 1601. Hauptmann, G., Grosshans, E., Heid, E. Boll. Ist. Sieroter. Milan, 1974, 53, 228. Schaller, J. Arthr. Rheum. 1971, 14, 411. Amman, A. J., Hong, R. Medicine, 1971, 50, 223.
18. Fudenberg, H. H. in Phagocytic Mechanisms in Health and Disease (edited by R. C. Williams and H. H. Fudenberg); Stuttgart, 1972.
Departments of Gastroenterology Hæmatology, Royal Children’s Hospital,
and
G. L. BARNES H. EKERT S.V. DOWLING
Parkville, Melbourne, Australia 3052.
1. Samuels, C. E., Elliott, R. B. Lancet, Sept. 2. Ekert, H., Sheers, M. J. thorac. cardiovasc.
PERCENTAGE OF N.B.T.-REDUCING CELLS IN S.L.E. PATIENTS AND
27, 1975, p. 607 Surg. 1974, 67, 184.
NORMAL CONTROLS
