Rheumatology and Rehabilitation, 1975,14,19
CARCINOEMBRYONIC ANTIGEN IN RHEUMATIC DISEASES* BY ARLEEN UNGER, G. S. PANAYI AND M. H. LESSOF Department of Medicine and Guy's Arthritis Research Unit Guy's Hospital Medical School, London SE1 9RT
CARCINOEMBRYONIC antigen was detected by Gold and Freedman (1965) when they raised an antiserum to colonic carcinoma. This antiserum, after suitable absorption, reacted with an antigen which at the time could only be detected in gastrointestinal carcinomas and in fetal gut. Purification of the antigen showed it to be a glycoprotein with a molecular weight of 150-200 000 daltons. A radio-immunoassay for its estimation was soon developed (Egan et al., 1972) and with this highly sensitive technique it is now possible to measure this antigen in normal plasma and to show raised levels not only in carcinomas of e.g. colon, pancreas and bronchus (Laurence et al., 1972), but also in inflammatory conditions such as ulcerative colitis (Moore, Kantrowitz and Zamcheck, 1972), pancreatitis (Khoo and Mackay, 1973) and bronchitis (Laurence et al, 1972). It was this latter association with inflammatory and hyperplastic conditions which prompted this present investigation of CEA in rheumatic diseases.
METHODS Details of CEA assay, blood samples and subjects studied can be found in the preliminary communication (Unger, Panayi and Lessof, 1974). In addition, 15 samples from patients with Sjogren's syndrome and 23 with Still's disease were also assayed. RHEUMATOID FACTOR TITRE
Rheumatoid factor was measured on serial dilutions of serum samples using the Latex Globulin Reagent (Hyland). *Paper presented at a combined meeting of the British Association for Rheumatology and Rehabilitation, the Heberden Society, the Rheumatology and Rehabilitation Section of the Royal Society of Medicine, and the Swiss Society for Rheumatology, Bristol, June 1974. 19
Downloaded from http://rheumatology.oxfordjournals.org/ at New York University on June 17, 2015
SUMMARY In an earlier study, the mean plasma carcinoembryonic antigen (CEA) level of patients with seropositive rheumatoid arthritis (RA) was found to be significantly higher than that of normal, control subjects. Levels of CEA in patients with seronegative RA and ankylosing spondylitis, however, did not differ from normal. In this study it was shown that the mean CEA level of 16 patients with Sjogren's syndrome was also significantly higher than normal (P=0.001), whereas in a group of 23 children with Still's disease the mean level fell within the normal adult range. Despite the apparent association between rheumatoid factor and raised plasma CEA, no correlation was found between titre of rheumatoid factor and CEA levels. Gel filtration studies indicated that the CEA in rheumatoid arthritis was of a similar molecular weight to that found in cancer of the colon and that there was minimal contribution by the known cross-reacting antigen CCEA2. The mean CEA level in rheumatoid synovia! fluids was found to be significantly higher than in osteoarthrotic fluids. A preliminary study has also shown that CEA can be extracted from rheumatoid synovial membranes but was not detected in a normal synovium, further indicating that the source of this antigen in RA may be the inflamed synovium.
20
RHEUMATOLOGY AND REHABILITATION VOL. XTV NO. 1
40
30
20
-tt" U 10 t
i. i
r
1
Normal
Ankylosing spondylitis
RA seronegative
RA seropositive
Sjogren's syndrome
Still's disease
FIG. 1.—Concentration of CEA in blood of normal subjects and patients with various rheumatic diseases. The line at 17.5 ng/ml CEA denotes the upper limit of normal which was derived by adding two standard deviations to the mean CEA level of the normal subjects. GEL FILTRATION
Plasma samples were fractionated by column chromatography (100x2.5 cm) using Sephadex G-200 (Pharmacia Ltd.) with 0.01 M-phosphate buffer (pH 7.1) containing 0.15 M-sodium chloride, 0.01 M-EDTA and 0.05% sodium azide. The flow rate was 15 ml/hour and 15 min fractions were collected.
RESULTS The individual CEA levels in the plasma of patients with Sjogren's syndrome and Still's disease are presented in Fig. 1. This also shows the levels in normal subjects and patients with ankylosing spondylitis and RA. The upper limit of normal was derived by adding two standard deviations to the mean CEA level of the group of normal subjects. Thus only one of 19 patients with ankylosing spondylitis and none of the seronegative RA patients had a high level of CEA in their plasma. Whereas eight of 19 patients with seropositive RA and nine of 15 patients with Sj6gren's syndrome had raised levels. The mean CEA levels of both these groups were statistically higher than that of the normal controls (P = 0.001). In Still's disease, although five patients had high CEA levels, the mean value was within the normal range.
Downloaded from http://rheumatology.oxfordjournals.org/ at New York University on June 17, 2015
o
UNGER ET AL.: CARCINOEMBRYONIC ANTIGEN :
21
Since there appeared to be an association between rheumatoid factor and increased plasma CEA, the possibility was considered that rheumatoid factor may be interfering with the CEA assay. However, no correlation was found between titre of rheumatoid factor and CEA level of 17 samples (Fig. 2). 10000 r-
100
10
20
30
40
50
CEA ng/ml
FIG. 2.—Rheumatoid factor titre and CEA concentration in 17 seropositive samples from seropositive RA and Sjogren's syndrome.
IDENTITY OF CEA IN RA
There are several reports of an antigen known as NCA (von Kleist, Chavanel and Burtin, 1972) or NGP (Mach and Pusztaszeri, 1972) or CCEA2 (Turberville et al., 1973) which can be extracted from colonic carcinoma along with CEA and can crossreact with it in the radio-immunoassay. However, most authors agree that it is of a lower molecular weight than CEA being more in the order of 60 000 daltons. Gel filtration studies were therefore undertaken to determine the molecular weight of CEA activity in rheumatoid plasma. These results are presented in Fig. 3. The results of fractionating 1 ml of plasma containing radio-labelled CEA or CCEA2 showed that both eluted in the expected positions, consistent with their known molecular weights of 200 000 and 60 000 respectively (Fig. 3, section A).
Downloaded from http://rheumatology.oxfordjournals.org/ at New York University on June 17, 2015
1000
22
RHEUMATOLOGY AND REHABILITATION VOL. XTV NO. 1
70 80
CEA in plasma of cancer patient
CEA In plasma of Sero-positive RA patient
pools
represents the elution of protein from 1 ml of normal plasma fractionated FIG. 3 A.on Sephadex G-200. O O represents elution of radioactivity from fractionation of 1 ml normal plasma containing 50 /xl 1MI CEA. % % represents elution of radioactivity from fractionation on same column of 1 ml normal plasma containing 50 /u.1125I CCEA-2. B.—1 ml plasma from a patient with carcinoma of bronchus was fractionated on the same column. Fractions contained within the broken vertical lines were pooled and concentrated by ultrafiltration. The CEA content of each pool is represented by the height of the shaded areas. C.—Represents the CEA content of the four pools when 1 ml plasma from a patient wit seropositive RA was fractionated on the same column.
When CEA was measured in the pooled fractions from the cancer plasma (Fig. 3, section B), 37% of the total CEA activity was found in the first pool, i.e. molecular weight greater than 200 000; 35% was found in the second pool (molecular weight consistent with CEA) and only 7 % in the fractions which would contain CCEA2. Measurement of CEA in the pooled fractions from rheumatoid plasma showed that, in contrast to the cancer plasma, no CEA activity was found in the first pool, 50% of the total CEA was contained in the second pool and only 12% in the fourth pool which would contain CCEA2. The CEA activity found in the third pools in both the cancer and rheumatoid plasma could represent catabolic products of CEA or another, as yet, unidentified cross-reacting antigen.
Downloaded from http://rheumatology.oxfordjournals.org/ at New York University on June 17, 2015
10 20 30 40 50 60
UNGER ET AL.: CARCINOEMBRYONIC ANTIGEN CEA
23
IN SYNOVIAL FLUIDS
CEA was measured in synovial fluids from 14 rheumatoid patients and four osteoarthrotic (OA) patients. The mean CEA level in the RAfluidswas 42.5±21.3 ng/ml whereas in the OA fluids it was only 13.8 ±12.4 ng/ml. This difference was statistically significant (P = 0.02). Preliminary results from a study now in progress show that CEA can be extracted from RA synovial membranes whereas in one normal synovium it was not detected.
ACKNOWLEDGMENTS
We wish to thank Professor A. Munro Neville and his staff at the Chester Beatty Research Institute for giving us access to their CEA radioimmunoassay. Dr. B. Ansell and Dr. C. Dick, kindly supplied the samples from the patients with Still's disease and Sjogren's syndrome. The work was supported by the Arthritis and Rheumatism Council. REFERENCES
M. L., LAUTENSCHLEGER, J. T., COLIGAN, J. E., and TODD, C. W. (1972) "Radioimmune Assay of Carcinoembryonic Antigen". Immunochemistry, 9, 289. GOLD, P., and FREEDMAN, S. O. (1965) "Specific Carcinoembryonic Antigens of the Human Digestive System". /. exp. Med., 122, 467. KHOO, S. K., and MACKAY, I. R. (1973) "Carcinoembryonic Antigen in Serum in Diseases of the Liver and Pancreas". /. Clin. Path., 26, 470. VON KLEIST, S., CHAVANEL, G., and BURTIN, P. (1972) Proc. Natl. Acad. Sci. (U.S.A.), 69, 2492. EGAN,
LAURENCE, D. J. R., STEVENS, U., BETTELHEIM, R., DARCY, D., LEESE, C, TURBERVILLE, C , ALEXANDER, P., JOHNS, E. W., and MUNRO NEVILLE, A. (1972) "Role of Plasma Carcino-
embryonic Antigen in the Diagnosis of Gastrointestinal, Mammary and Bronchial Carcinoma." Br. med. J., 3, 605. MACH, J. P., and PUSZTASZERJ, G. (1972) "Carcinoembryonic Antigen (CEA): Demonstration of a Partial Identity between CEA and a Normal Glycoprotein". Immunochemistry, 9, 1031. MOORE, T. L., KANTROWTTZ, P. A., and ZAMCHECK, N. (1972) "Carcinoembryonic Antigen (CEA) in Inflammatory Bowel Disease". 222, 94.
Downloaded from http://rheumatology.oxfordjournals.org/ at New York University on June 17, 2015
DISCUSSION Raised levels of CEA have been detected in seropositive RA and Sjogren's syndrome. No correlation was found between rheumatoid factor titre and CEA levels suggesting that the former does not interfere with the CEA assay system. The gel filtration studies indicated that the major part of the CEA activity in RA plasma is of a similar molecular weight to that extracted from colonic carcinoma and that there was minimal contribution by the known cross-reacting antigen CCEA2. The finding that the mean concentration of CEA in rheumatoid synovial fluids was significantly higher than that in osteoarthrotic fluids might mean that the CEA in RA is derived from the inflamed synovium. This suggestion was further supported by the observation that CEA could be extracted from rheumatoid synovial membranes but was not detected in a normal synovium. The clinical significance of CEA in rheumatoid arthritis has yet to be assessed in a prospective study in which plasma CEA, disease activity, duration of disease and drug treatment will be monitored. To date, most studies on CEA have concentrated on neoplastic conditions and those pre-disposed to malignancy. This present investigation of CEA in rheumatoid arthritis may therefore make a contribution not only to the study of rheumatic disease but may also be of some value in tumour biology.
24
RHEUMATOLOGY AND REHABILITATION VOL. XIV NO. 1
TURBERVILLE, C , DARCY, D. A., LAURENCE, D. J. R., JOHNS, E. W., and MUNRO NEVILLE, A.
(1973) "Studies on Carcinoembryonic Antigen (CEA) and a Related Glycoprotein CCEA-2. Preparation and Chemical Characterisation". Immunochemistry, 10, 841. UNGER, A., PANAYI, G. S., and LESSOF, M. H. (1974) "Carcinoembryonic Antigen in Rheumatoid Arthritis". Lancet, i, 781. GENERAL DISCUSSION (ABRIDGED) M. L. SNAJTH (Oxford): It seems possible that the presence of raised levels of CEA coincides with situations where there is generalized lymphoid proliferation. Have you used as disease controls other conditions such as infectious mononucleosus, sarcoid etc., where there is a proliferation of lymphocytes ? DR.
know where CEA comes from in the cells? has been reported to be on the cell surface, although in gastric carcinoma we found CEA in the cytoplasm. As yet we have no evidence for the site of CEA in the rheumatoid synovial membrane. DR. B. VERNON-ROBERTS (London): Could CEA be involved in leucocyte migration inhibition ? DR. UNGER: The same thought occurred to me. As yet there is no evidence that CEA is immunogenic in cancer patients. No one has shown altered immunity on skin testing or with other immunological tests. There is still controversy as to whether there is a naturally occurring antibody to CEA. DR. ZAPHIROPOULOS (Coventry): Did you find any variability in these levels say from week to week or month to month ? Can you correlate your results with the rheumatoid factor titre? Did you find any correlation between the plasma and the synovial levels of CEA? DR. UNGER : There was no direct correlation between plasma and synovial levels. Synovial levels were always higher. We have done some serial studies and generally if they are high they remain high and if they are low they remain low, but we really need a prospective study.
Downloaded from http://rheumatology.oxfordjournals.org/ at New York University on June 17, 2015
DR. UNGER: NO. DR. K. FEHR (Zurich): Do you DR. UNGER : In tumours, CEA
CARCINOEMBRYONIC ANTIGEN IN RHEUMATIC DISEASES* BY ARLEEN UNGER, G. S. PANAYI AND M. H. LESSOF Department of Medicine and Guy's Arthritis Research Unit Guy's Hospital Medical School, London SE1 9RT
CARCINOEMBRYONIC antigen was detected by Gold and Freedman (1965) when they raised an antiserum to colonic carcinoma. This antiserum, after suitable absorption, reacted with an antigen which at the time could only be detected in gastrointestinal carcinomas and in fetal gut. Purification of the antigen showed it to be a glycoprotein with a molecular weight of 150-200 000 daltons. A radio-immunoassay for its estimation was soon developed (Egan et al., 1972) and with this highly sensitive technique it is now possible to measure this antigen in normal plasma and to show raised levels not only in carcinomas of e.g. colon, pancreas and bronchus (Laurence et al., 1972), but also in inflammatory conditions such as ulcerative colitis (Moore, Kantrowitz and Zamcheck, 1972), pancreatitis (Khoo and Mackay, 1973) and bronchitis (Laurence et al, 1972). It was this latter association with inflammatory and hyperplastic conditions which prompted this present investigation of CEA in rheumatic diseases.
METHODS Details of CEA assay, blood samples and subjects studied can be found in the preliminary communication (Unger, Panayi and Lessof, 1974). In addition, 15 samples from patients with Sjogren's syndrome and 23 with Still's disease were also assayed. RHEUMATOID FACTOR TITRE
Rheumatoid factor was measured on serial dilutions of serum samples using the Latex Globulin Reagent (Hyland). *Paper presented at a combined meeting of the British Association for Rheumatology and Rehabilitation, the Heberden Society, the Rheumatology and Rehabilitation Section of the Royal Society of Medicine, and the Swiss Society for Rheumatology, Bristol, June 1974. 19
Downloaded from http://rheumatology.oxfordjournals.org/ at New York University on June 17, 2015
SUMMARY In an earlier study, the mean plasma carcinoembryonic antigen (CEA) level of patients with seropositive rheumatoid arthritis (RA) was found to be significantly higher than that of normal, control subjects. Levels of CEA in patients with seronegative RA and ankylosing spondylitis, however, did not differ from normal. In this study it was shown that the mean CEA level of 16 patients with Sjogren's syndrome was also significantly higher than normal (P=0.001), whereas in a group of 23 children with Still's disease the mean level fell within the normal adult range. Despite the apparent association between rheumatoid factor and raised plasma CEA, no correlation was found between titre of rheumatoid factor and CEA levels. Gel filtration studies indicated that the CEA in rheumatoid arthritis was of a similar molecular weight to that found in cancer of the colon and that there was minimal contribution by the known cross-reacting antigen CCEA2. The mean CEA level in rheumatoid synovia! fluids was found to be significantly higher than in osteoarthrotic fluids. A preliminary study has also shown that CEA can be extracted from rheumatoid synovial membranes but was not detected in a normal synovium, further indicating that the source of this antigen in RA may be the inflamed synovium.
20
RHEUMATOLOGY AND REHABILITATION VOL. XTV NO. 1
40
30
20
-tt" U 10 t
i. i
r
1
Normal
Ankylosing spondylitis
RA seronegative
RA seropositive
Sjogren's syndrome
Still's disease
FIG. 1.—Concentration of CEA in blood of normal subjects and patients with various rheumatic diseases. The line at 17.5 ng/ml CEA denotes the upper limit of normal which was derived by adding two standard deviations to the mean CEA level of the normal subjects. GEL FILTRATION
Plasma samples were fractionated by column chromatography (100x2.5 cm) using Sephadex G-200 (Pharmacia Ltd.) with 0.01 M-phosphate buffer (pH 7.1) containing 0.15 M-sodium chloride, 0.01 M-EDTA and 0.05% sodium azide. The flow rate was 15 ml/hour and 15 min fractions were collected.
RESULTS The individual CEA levels in the plasma of patients with Sjogren's syndrome and Still's disease are presented in Fig. 1. This also shows the levels in normal subjects and patients with ankylosing spondylitis and RA. The upper limit of normal was derived by adding two standard deviations to the mean CEA level of the group of normal subjects. Thus only one of 19 patients with ankylosing spondylitis and none of the seronegative RA patients had a high level of CEA in their plasma. Whereas eight of 19 patients with seropositive RA and nine of 15 patients with Sj6gren's syndrome had raised levels. The mean CEA levels of both these groups were statistically higher than that of the normal controls (P = 0.001). In Still's disease, although five patients had high CEA levels, the mean value was within the normal range.
Downloaded from http://rheumatology.oxfordjournals.org/ at New York University on June 17, 2015
o
UNGER ET AL.: CARCINOEMBRYONIC ANTIGEN :
21
Since there appeared to be an association between rheumatoid factor and increased plasma CEA, the possibility was considered that rheumatoid factor may be interfering with the CEA assay. However, no correlation was found between titre of rheumatoid factor and CEA level of 17 samples (Fig. 2). 10000 r-
100
10
20
30
40
50
CEA ng/ml
FIG. 2.—Rheumatoid factor titre and CEA concentration in 17 seropositive samples from seropositive RA and Sjogren's syndrome.
IDENTITY OF CEA IN RA
There are several reports of an antigen known as NCA (von Kleist, Chavanel and Burtin, 1972) or NGP (Mach and Pusztaszeri, 1972) or CCEA2 (Turberville et al., 1973) which can be extracted from colonic carcinoma along with CEA and can crossreact with it in the radio-immunoassay. However, most authors agree that it is of a lower molecular weight than CEA being more in the order of 60 000 daltons. Gel filtration studies were therefore undertaken to determine the molecular weight of CEA activity in rheumatoid plasma. These results are presented in Fig. 3. The results of fractionating 1 ml of plasma containing radio-labelled CEA or CCEA2 showed that both eluted in the expected positions, consistent with their known molecular weights of 200 000 and 60 000 respectively (Fig. 3, section A).
Downloaded from http://rheumatology.oxfordjournals.org/ at New York University on June 17, 2015
1000
22
RHEUMATOLOGY AND REHABILITATION VOL. XTV NO. 1
70 80
CEA in plasma of cancer patient
CEA In plasma of Sero-positive RA patient
pools
represents the elution of protein from 1 ml of normal plasma fractionated FIG. 3 A.on Sephadex G-200. O O represents elution of radioactivity from fractionation of 1 ml normal plasma containing 50 /xl 1MI CEA. % % represents elution of radioactivity from fractionation on same column of 1 ml normal plasma containing 50 /u.1125I CCEA-2. B.—1 ml plasma from a patient with carcinoma of bronchus was fractionated on the same column. Fractions contained within the broken vertical lines were pooled and concentrated by ultrafiltration. The CEA content of each pool is represented by the height of the shaded areas. C.—Represents the CEA content of the four pools when 1 ml plasma from a patient wit seropositive RA was fractionated on the same column.
When CEA was measured in the pooled fractions from the cancer plasma (Fig. 3, section B), 37% of the total CEA activity was found in the first pool, i.e. molecular weight greater than 200 000; 35% was found in the second pool (molecular weight consistent with CEA) and only 7 % in the fractions which would contain CCEA2. Measurement of CEA in the pooled fractions from rheumatoid plasma showed that, in contrast to the cancer plasma, no CEA activity was found in the first pool, 50% of the total CEA was contained in the second pool and only 12% in the fourth pool which would contain CCEA2. The CEA activity found in the third pools in both the cancer and rheumatoid plasma could represent catabolic products of CEA or another, as yet, unidentified cross-reacting antigen.
Downloaded from http://rheumatology.oxfordjournals.org/ at New York University on June 17, 2015
10 20 30 40 50 60
UNGER ET AL.: CARCINOEMBRYONIC ANTIGEN CEA
23
IN SYNOVIAL FLUIDS
CEA was measured in synovial fluids from 14 rheumatoid patients and four osteoarthrotic (OA) patients. The mean CEA level in the RAfluidswas 42.5±21.3 ng/ml whereas in the OA fluids it was only 13.8 ±12.4 ng/ml. This difference was statistically significant (P = 0.02). Preliminary results from a study now in progress show that CEA can be extracted from RA synovial membranes whereas in one normal synovium it was not detected.
ACKNOWLEDGMENTS
We wish to thank Professor A. Munro Neville and his staff at the Chester Beatty Research Institute for giving us access to their CEA radioimmunoassay. Dr. B. Ansell and Dr. C. Dick, kindly supplied the samples from the patients with Still's disease and Sjogren's syndrome. The work was supported by the Arthritis and Rheumatism Council. REFERENCES
M. L., LAUTENSCHLEGER, J. T., COLIGAN, J. E., and TODD, C. W. (1972) "Radioimmune Assay of Carcinoembryonic Antigen". Immunochemistry, 9, 289. GOLD, P., and FREEDMAN, S. O. (1965) "Specific Carcinoembryonic Antigens of the Human Digestive System". /. exp. Med., 122, 467. KHOO, S. K., and MACKAY, I. R. (1973) "Carcinoembryonic Antigen in Serum in Diseases of the Liver and Pancreas". /. Clin. Path., 26, 470. VON KLEIST, S., CHAVANEL, G., and BURTIN, P. (1972) Proc. Natl. Acad. Sci. (U.S.A.), 69, 2492. EGAN,
LAURENCE, D. J. R., STEVENS, U., BETTELHEIM, R., DARCY, D., LEESE, C, TURBERVILLE, C , ALEXANDER, P., JOHNS, E. W., and MUNRO NEVILLE, A. (1972) "Role of Plasma Carcino-
embryonic Antigen in the Diagnosis of Gastrointestinal, Mammary and Bronchial Carcinoma." Br. med. J., 3, 605. MACH, J. P., and PUSZTASZERJ, G. (1972) "Carcinoembryonic Antigen (CEA): Demonstration of a Partial Identity between CEA and a Normal Glycoprotein". Immunochemistry, 9, 1031. MOORE, T. L., KANTROWTTZ, P. A., and ZAMCHECK, N. (1972) "Carcinoembryonic Antigen (CEA) in Inflammatory Bowel Disease". 222, 94.
Downloaded from http://rheumatology.oxfordjournals.org/ at New York University on June 17, 2015
DISCUSSION Raised levels of CEA have been detected in seropositive RA and Sjogren's syndrome. No correlation was found between rheumatoid factor titre and CEA levels suggesting that the former does not interfere with the CEA assay system. The gel filtration studies indicated that the major part of the CEA activity in RA plasma is of a similar molecular weight to that extracted from colonic carcinoma and that there was minimal contribution by the known cross-reacting antigen CCEA2. The finding that the mean concentration of CEA in rheumatoid synovial fluids was significantly higher than that in osteoarthrotic fluids might mean that the CEA in RA is derived from the inflamed synovium. This suggestion was further supported by the observation that CEA could be extracted from rheumatoid synovial membranes but was not detected in a normal synovium. The clinical significance of CEA in rheumatoid arthritis has yet to be assessed in a prospective study in which plasma CEA, disease activity, duration of disease and drug treatment will be monitored. To date, most studies on CEA have concentrated on neoplastic conditions and those pre-disposed to malignancy. This present investigation of CEA in rheumatoid arthritis may therefore make a contribution not only to the study of rheumatic disease but may also be of some value in tumour biology.
24
RHEUMATOLOGY AND REHABILITATION VOL. XIV NO. 1
TURBERVILLE, C , DARCY, D. A., LAURENCE, D. J. R., JOHNS, E. W., and MUNRO NEVILLE, A.
(1973) "Studies on Carcinoembryonic Antigen (CEA) and a Related Glycoprotein CCEA-2. Preparation and Chemical Characterisation". Immunochemistry, 10, 841. UNGER, A., PANAYI, G. S., and LESSOF, M. H. (1974) "Carcinoembryonic Antigen in Rheumatoid Arthritis". Lancet, i, 781. GENERAL DISCUSSION (ABRIDGED) M. L. SNAJTH (Oxford): It seems possible that the presence of raised levels of CEA coincides with situations where there is generalized lymphoid proliferation. Have you used as disease controls other conditions such as infectious mononucleosus, sarcoid etc., where there is a proliferation of lymphocytes ? DR.
know where CEA comes from in the cells? has been reported to be on the cell surface, although in gastric carcinoma we found CEA in the cytoplasm. As yet we have no evidence for the site of CEA in the rheumatoid synovial membrane. DR. B. VERNON-ROBERTS (London): Could CEA be involved in leucocyte migration inhibition ? DR. UNGER: The same thought occurred to me. As yet there is no evidence that CEA is immunogenic in cancer patients. No one has shown altered immunity on skin testing or with other immunological tests. There is still controversy as to whether there is a naturally occurring antibody to CEA. DR. ZAPHIROPOULOS (Coventry): Did you find any variability in these levels say from week to week or month to month ? Can you correlate your results with the rheumatoid factor titre? Did you find any correlation between the plasma and the synovial levels of CEA? DR. UNGER : There was no direct correlation between plasma and synovial levels. Synovial levels were always higher. We have done some serial studies and generally if they are high they remain high and if they are low they remain low, but we really need a prospective study.
Downloaded from http://rheumatology.oxfordjournals.org/ at New York University on June 17, 2015
DR. UNGER: NO. DR. K. FEHR (Zurich): Do you DR. UNGER : In tumours, CEA
