Leukemia and Lymphoma, Vol. 7, pp. 117-122 Reprints available directly from the publisher Photocopying permitted by license only
0 1992 Harwood Academic Publishers GmbH Printed in the United Kingdom
Autoantibodies in the Sera of Patients with Lymphoma Leuk Lymphoma Downloaded from informahealthcare.com by University of Alberta on 01/14/15 For personal use only.
M. SWISSA’, Y. COHEN2 and Y.SHOENFELD’ ‘Research Unit of Autoimmune Diseases, and the Department of Medicine “B”, Sheba Medical Center, Tel-Hashomer, Tel-Aviv University, Sackler School of Medicine, and ’Department of Oncology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Soroka Medical Center, Beer-Sheva, Israel. (Received 25 November 1991)
Sera of 84 patients with Hodgkin’s disease (HD) and 55 patients with non-Hodgkin’s lymphoma (NHL) were examined for the presence of autoantibodies to ssDNA, dsDNA, Poly (I), Poly (G), cardiolipin, histones, RNP. Sm, Ro (SS/A), La (SS/B) and the common anti-DNA idiotype (16/6) using an enzyme-linked immunosorbent assay (ELISA). Anti-ssDNA antibodies were detected in the sera of 20 patients with lymphoma (23.8%), more among those with N H L than H D (16 vs. 4 patients p < 0.01). Anti-RNP and anti-Sm antibodies were found in 16 (21.7%) and 14 lymphoma patients (20%) respectively, significantly more than in the controls (p < 0.05) in both antibodies). These findings remained valid following subgrouping of the patients into those with H D and NHL. With all the other autoantibodies examined no significant difference could be observed in the incidence between lymphoma patients and controls. These results differ from our previous survey carried out on sera of patients with solid tumors in whom no increased frequency of any of the autoantibodies could be determined. In view of the evidence suggesting an increased risk of lymphoma in a number of autoimmune diseases our results extend this relationship to an increased incidence of autoantibodies among patients with lymphoma. KEY WORDS:
Non Hodgkin’s lymphoma autoimmunity
Hodgkin’s lymphoma autoantibodies
INTRODUCTION There are many reports on the association of immune mediated diseases and neoplasia’a2. Patients with autoimmune conditions develop neoplastic diseases, especially lymphoma, more frequently than the general p o p ~ l a t i o n ~Analogously, .~. various autoantibodies have been detected in sera of patients with both hematologic and epithelial malignancies’-’. Antinuclear antibodies were reported at a frequency of 19-27% among patients with cancer, especially in those with epithelial neoplasiaSa8, but also among those with leukemia’. Other autoantibodies that were
Address for correspondence: Professor Y. Shoenfeld, M.D., Head of Department of Medicine “B”, Sheba Medical Center, Tel-Hashomer 52621, Israel.
reported in the sera of patients with malignancies, include circulating anti-smooth muscle antibodies’, anti- perinuclear factor”, rheumatoid factor’ ‘ * 1 2 , and immune complexes’ 3*14. Recent studies have also shown an increased incidence of reticuloendothelial cancers, especially various lymphomas, among patients with rheumatoid arthritis (RA)14*’’. The relative risk for lymphoma in RA patients was estimated at 2.7 compared with the risk in the general population”-”. The association between Sjogren’s syndrome ( S S ) and lymphoma is the strongest and appears to be the most prominent among the immune mediated diseases’. In one report 7 of 136 patients with sicca syndrome developed non-Hodgkin’s lymphoma, 44 times the frequency expected from the rates of cancer prevailing among women of the same age range in the general population4.
117
Leuk Lymphoma Downloaded from informahealthcare.com by University of Alberta on 01/14/15 For personal use only.
I I8
M. SWISSA, Y. COHEN AND Y. SHOENFELD
Recently' ', we have analyzed a relatively large and diverse group of patients with epithelial tumors and found no significant increase in the incidence of autoantibodies in comparison to age and sex matched control groups. We believe that in previous reports in which the subjects were not matched for age, the increased incidence noted with cancer was probably due to the older age of the cancer patients. Despite the numerous reports on the incidence of autoantibodies in solid tumors, very few studies have analyzed the incidence of autoantibodies in the sera of patients with lymphoma. In the current study we evaluated the sera of 84 patients with HD and NHL along with the sera 46 age and sex matched controls for the presence of diverse anti-nuclear autoantibodies and compared the frequency of autoantibody detection in the patient group to that of the control group.
MATERIAL AND METHODS Patients' sera Sera were obtained from 84 patients with lymphoma. Fifty one of the patients were males, and 33 were females. The patients were subdivided into two groups: 29 patients with H D (18 males and 11 females), and 55 patients with NHL (33 males and 22 females).As controls we used 46 sera samples obtained from healthy subjects (23 males and 23 females), matched for their ages with the study group.
wells and incubated for 1 hr at 23°C. The plates were then washed with 0.05% tween -20 in TBS (Tween-TBS) and TBS (tris buffer solution, pH 7.4). Alkaline phosphatase conjugated goat anti-human IgG, IgM and IgA (Sigma) was added at a 1: lo00 dilution in 5% BS-TBS and the plates were developed and read by adding p-nitrophenyl phosphate (1 mg/ml) in 0.5 M NaHCO, with 2 m M MgCI, (pH = 9.5) at room temperature. Absorbance at 405nm was read by a Dynatech model MR 600 ELISA reader. Assay detecting anti-histone antibodies ELISA was used to detect antibodies to total histones. The total histones were prepared as previously described20*21.Polystyrene plates (Immunolon 11, Dynatech lab-inc) were coated with 150uL of the histone preparation, diluted in 0.06-M NaHCO,, pH 9.6 at a concentration of 10ug/ml overnight at 4". After four washes with phosphate buffered saline (PBS), the plates were incubated for two hours at 37°C in PBS containing 2% bovine serum albumin. Thereafter, the test sera diluted 1:200 in PBS-0.05% tween -20, were incubated in the plates for two hours at 37°C. The wells were then washed with 1 M NaCI in 0.025 M sodium borate, 0.1 M boric acid buffer, pH 8.3 and 0.1% tween (BBS buffer), followed by PBS -0.1 % tween and PBS. Alkaline phosphatase conjugated goat anti-human IgG, IgM and IgA (Sigma) was added at a 1:1o00 dilution and the plates were developed and read as detailed above.
ssDNA, dsDNA, poly (I), poly (C) and cardiolipin Denatured and native DNA were prepared as described previously'8. Poly (I), poly (G) and cardiolipin were purchased from Sigma, U.S.A.
Assay detecting anti-RNP, anti-Sm, anti-Ro (SSA) and anti-La (SSB) antibodies
Antibodies against the autoantigens RNP, Sm, Ro (SS-A) and La (SS-B) were determined by the methods ~ ~characteristics . mentioned by Mendlovic et ~ 1 , The Assays for serum antibody reacting with of these autoantigens were recently established by the polynucleotides immunoblot a s ~ a y ~Briefly, ~ . ~ ~following . coating of Antibodies against polynucleotides and cardiolipin polystyrene plates with 5.0 ug/ml of the antigen, the were assayed by ELISA as previously described' 8*19. plates were blocked with 5% bovine serum and In brief, polystyrene plates (Immunolon 11, Dynatech incubated with the subjects' sera diluted 1:200 in TBS laboratories, Inc.) were coated with poly-L-lysine for one hour in 37°C and then washed three times (50 ug/ml), the antigen to be screened (2.5 ug/ml) and with 0.05% tween -20 in PBS. The microtiter wells poly-L-glutamate (50 ug/ml). The sera were diluted were then incubated at 37°C for one hour with with 2% bovine serum in tris buffer saline (BS-TBS) anti-human immunoglobulin alkaline phosphotase and used in the assay at a dilution of 1: 200. One conjugated. The reaction was continued hence hundred and fifty ml of the sera were added to the forward as described above.
AUTOANTIBODIES IN LYMPHOMA
119
while anti-Sm, and anti SSB were found in 16.7% and 14.3% respectively. Other autoantibodies could be The anti-idiotypic sera (R-anti-16/6)were prepared by detected in less than 10% of the sera. The increased monthly immunization of rabbits with monocolonal frequency of anti-ssDNA, anti-RNP and anti-Sm lupus anti-DNA antibodies, as detailed previouslyz5. autoantibodies was statistically significant as compared to controls ( p < 0.01, p e 0.05, respectively). Detection of idiotypes in sera of patients with Production of anti-idiotype antibodies
Leuk Lymphoma Downloaded from informahealthcare.com by University of Alberta on 01/14/15 For personal use only.
lymphoma
Polystyrene plates containing 96 wells (Nunc) were incubated with serum diluted in 0.05 M borate buffer for 18 hr at 4°C and then washed three times with 1% tween - 20 phosphate-buffered saline (1YO T-PBS) and PBS. Titration curves with dilutions of normal and lupus serum that extended over three orders of magnitude were carried out to select optimal dilutions for the assay27. The optimal serum dilutions were close to the midpoints of the slopes of the titration curves (1: 10,000). The anti-idiotypic serum was diluted (1:12,000 for 16/6). In 0.1% T-PBS and added to the serum-coated wells. After incubation for 2 hr at room temperature the plates were washed three times with 1% T-PBS and blocked with PBS-l% BSA for 2 hr and 150 ul of goat anti-rabbit immunoglobulin conjugated to alkaline phosphatase was added. The plates were then incubated overnight at room temperature. Determination of the bound alkaline phosphatase conjugate was detected by the addition of 150 uL p- nitrophenyl phosphate (1 mg/ml in 0.5 M NaHCO,, 2 mM MgCl,, pH 9.5, at 23°C).The optical densities were read as detailed above.
Autoantibodies in the sera of patients with non-Hodgkin’s and Hodgkin’s lymphoma
Tables 2-4 summarize the frequency of autoantibodies separately in patients with NHL and HD. It seems that patients with NHL differ from those with HD by having significantly increased titers of anti-dsDNA and a greater tendency toward anti-ssDNA antibodies. Polyspecificity of sera of patients with lymphoma
Thirty three sera of the 84 lymphoma patients were positive for at least one antigen; 20 were found to react with ssDNA, 19 with RNP, 14 with Sm, 12 with SSB, 8 with Poly (G),7 with SSA, 6 with cardiolipin, 4 with Poly (I), 1 with histones and none with the 16/6 Id. Among those 33 sera; 9 were found to react with one antigen, 6 with 2 antigens, 7 with 3 antigens, 4 with 4 antigens, 4 with 5 antigens and three with 6,7 and 8 antigens, respectively.
DISCUSSION
Autoimmune diseases and cancer are being diagnosed with increasing frequency, and there are many reports of an association between immune-mediated diseases ELISA values above the mean + 2 SD of the normal and neoplasia6*8*’6. In addition to the conventional sera were considered positive, an index shown autoantibodies such as anti-ssDNA and antipreviously to differentiate “normal” values from high his tone^^^.^^, novel autoantibodies were reported to valuesz7.The percentage of the high titer sera samples be associated with new clinical syndromes3’. was compared to the normal controls by the In contrast to previous reports, we have recently chi-square test. described an equal prevalence of a wide spectrum of anti-nuclear autoantibodies in the sera of 164 patients with various solid tumors as compared to a control RESULTS group, matched for both age and sex17. The increased incidence of autoantibodies in the sera of patients with Detection of autoantibodies in the sera of patients solid tumors reported by others was probably due to with lymphoma the older age of the patients with malignancies3’, The binding of patients and control sera to different rather than to the presence of the tumor. antigens is shown in Figures la and l b and Table 1. In the present study we extended the analysis to It can be seen that anti-ssDNA antibodies were found include patients with non-Hodgkin’s and Hodgkin’s in 23.8% of the patients with lymphoma (including lymphoma, employing the ELISA method to detect a HD and NHL). In 19.5% anti-RNP was detected diverse range of autoantibodies. In contrast to our Statistical analysis
0
0
Leuk Lymphoma Downloaded from informahealthcare.com by University of Alberta on 01/14/15 For personal use only.
t
! .
f 1 1 3 E
0.0 xd
Anti Sm
AntiRNP AntiSSA AntiSSB Anti'WkId
...
60
. .. ib t
-
0
40
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0
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: 0
10(
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.
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Figure l(e), (b) The frequency of antinuclear antibodies in the sera of patients with lymphoma compared to normal controls (NC) matched for age and sex. (anti-1616 id: anti-common anti-DNA idiotype-16/6).
AUTOANTIBODIES IN LYMPHOMA
Table 1 Frequency of auto-antibodies detected among 84 patients with lymphoma and 46 age adjusted normal-controls Autoantibody to
ssDNA dsDNA POIY (1) Poly (GI
Sm RNP
Leuk Lymphoma Downloaded from informahealthcare.com by University of Alberta on 01/14/15 For personal use only.
SS/A
SS/B Cardiolipin Histones 1616 Id
Lymphomu pat ient s
Normal controls
n = 84 20 (23.8%) 6 (7.I yo) 4 (4.8%) 8 (9.5%) 14 (16.7%) 16 (19.5%) 7 (8.3%) 12 (14.3%) 5 (6%) 1 (1.2%) 0 (0%)
n = 46 2 (4.3%) 4 (8.7%) 4 (8.7%) 4 (8.7%) 1 (2.2%) 2 (4.3%) 5 (10.9%) 3 (6.5%) 3 (6.5%) 3 (6.5%) 1 (2.2%)
0 1992 Harwood Academic Publishers GmbH Printed in the United Kingdom
Autoantibodies in the Sera of Patients with Lymphoma Leuk Lymphoma Downloaded from informahealthcare.com by University of Alberta on 01/14/15 For personal use only.
M. SWISSA’, Y. COHEN2 and Y.SHOENFELD’ ‘Research Unit of Autoimmune Diseases, and the Department of Medicine “B”, Sheba Medical Center, Tel-Hashomer, Tel-Aviv University, Sackler School of Medicine, and ’Department of Oncology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Soroka Medical Center, Beer-Sheva, Israel. (Received 25 November 1991)
Sera of 84 patients with Hodgkin’s disease (HD) and 55 patients with non-Hodgkin’s lymphoma (NHL) were examined for the presence of autoantibodies to ssDNA, dsDNA, Poly (I), Poly (G), cardiolipin, histones, RNP. Sm, Ro (SS/A), La (SS/B) and the common anti-DNA idiotype (16/6) using an enzyme-linked immunosorbent assay (ELISA). Anti-ssDNA antibodies were detected in the sera of 20 patients with lymphoma (23.8%), more among those with N H L than H D (16 vs. 4 patients p < 0.01). Anti-RNP and anti-Sm antibodies were found in 16 (21.7%) and 14 lymphoma patients (20%) respectively, significantly more than in the controls (p < 0.05) in both antibodies). These findings remained valid following subgrouping of the patients into those with H D and NHL. With all the other autoantibodies examined no significant difference could be observed in the incidence between lymphoma patients and controls. These results differ from our previous survey carried out on sera of patients with solid tumors in whom no increased frequency of any of the autoantibodies could be determined. In view of the evidence suggesting an increased risk of lymphoma in a number of autoimmune diseases our results extend this relationship to an increased incidence of autoantibodies among patients with lymphoma. KEY WORDS:
Non Hodgkin’s lymphoma autoimmunity
Hodgkin’s lymphoma autoantibodies
INTRODUCTION There are many reports on the association of immune mediated diseases and neoplasia’a2. Patients with autoimmune conditions develop neoplastic diseases, especially lymphoma, more frequently than the general p o p ~ l a t i o n ~Analogously, .~. various autoantibodies have been detected in sera of patients with both hematologic and epithelial malignancies’-’. Antinuclear antibodies were reported at a frequency of 19-27% among patients with cancer, especially in those with epithelial neoplasiaSa8, but also among those with leukemia’. Other autoantibodies that were
Address for correspondence: Professor Y. Shoenfeld, M.D., Head of Department of Medicine “B”, Sheba Medical Center, Tel-Hashomer 52621, Israel.
reported in the sera of patients with malignancies, include circulating anti-smooth muscle antibodies’, anti- perinuclear factor”, rheumatoid factor’ ‘ * 1 2 , and immune complexes’ 3*14. Recent studies have also shown an increased incidence of reticuloendothelial cancers, especially various lymphomas, among patients with rheumatoid arthritis (RA)14*’’. The relative risk for lymphoma in RA patients was estimated at 2.7 compared with the risk in the general population”-”. The association between Sjogren’s syndrome ( S S ) and lymphoma is the strongest and appears to be the most prominent among the immune mediated diseases’. In one report 7 of 136 patients with sicca syndrome developed non-Hodgkin’s lymphoma, 44 times the frequency expected from the rates of cancer prevailing among women of the same age range in the general population4.
117
Leuk Lymphoma Downloaded from informahealthcare.com by University of Alberta on 01/14/15 For personal use only.
I I8
M. SWISSA, Y. COHEN AND Y. SHOENFELD
Recently' ', we have analyzed a relatively large and diverse group of patients with epithelial tumors and found no significant increase in the incidence of autoantibodies in comparison to age and sex matched control groups. We believe that in previous reports in which the subjects were not matched for age, the increased incidence noted with cancer was probably due to the older age of the cancer patients. Despite the numerous reports on the incidence of autoantibodies in solid tumors, very few studies have analyzed the incidence of autoantibodies in the sera of patients with lymphoma. In the current study we evaluated the sera of 84 patients with HD and NHL along with the sera 46 age and sex matched controls for the presence of diverse anti-nuclear autoantibodies and compared the frequency of autoantibody detection in the patient group to that of the control group.
MATERIAL AND METHODS Patients' sera Sera were obtained from 84 patients with lymphoma. Fifty one of the patients were males, and 33 were females. The patients were subdivided into two groups: 29 patients with H D (18 males and 11 females), and 55 patients with NHL (33 males and 22 females).As controls we used 46 sera samples obtained from healthy subjects (23 males and 23 females), matched for their ages with the study group.
wells and incubated for 1 hr at 23°C. The plates were then washed with 0.05% tween -20 in TBS (Tween-TBS) and TBS (tris buffer solution, pH 7.4). Alkaline phosphatase conjugated goat anti-human IgG, IgM and IgA (Sigma) was added at a 1: lo00 dilution in 5% BS-TBS and the plates were developed and read by adding p-nitrophenyl phosphate (1 mg/ml) in 0.5 M NaHCO, with 2 m M MgCI, (pH = 9.5) at room temperature. Absorbance at 405nm was read by a Dynatech model MR 600 ELISA reader. Assay detecting anti-histone antibodies ELISA was used to detect antibodies to total histones. The total histones were prepared as previously described20*21.Polystyrene plates (Immunolon 11, Dynatech lab-inc) were coated with 150uL of the histone preparation, diluted in 0.06-M NaHCO,, pH 9.6 at a concentration of 10ug/ml overnight at 4". After four washes with phosphate buffered saline (PBS), the plates were incubated for two hours at 37°C in PBS containing 2% bovine serum albumin. Thereafter, the test sera diluted 1:200 in PBS-0.05% tween -20, were incubated in the plates for two hours at 37°C. The wells were then washed with 1 M NaCI in 0.025 M sodium borate, 0.1 M boric acid buffer, pH 8.3 and 0.1% tween (BBS buffer), followed by PBS -0.1 % tween and PBS. Alkaline phosphatase conjugated goat anti-human IgG, IgM and IgA (Sigma) was added at a 1:1o00 dilution and the plates were developed and read as detailed above.
ssDNA, dsDNA, poly (I), poly (C) and cardiolipin Denatured and native DNA were prepared as described previously'8. Poly (I), poly (G) and cardiolipin were purchased from Sigma, U.S.A.
Assay detecting anti-RNP, anti-Sm, anti-Ro (SSA) and anti-La (SSB) antibodies
Antibodies against the autoantigens RNP, Sm, Ro (SS-A) and La (SS-B) were determined by the methods ~ ~characteristics . mentioned by Mendlovic et ~ 1 , The Assays for serum antibody reacting with of these autoantigens were recently established by the polynucleotides immunoblot a s ~ a y ~Briefly, ~ . ~ ~following . coating of Antibodies against polynucleotides and cardiolipin polystyrene plates with 5.0 ug/ml of the antigen, the were assayed by ELISA as previously described' 8*19. plates were blocked with 5% bovine serum and In brief, polystyrene plates (Immunolon 11, Dynatech incubated with the subjects' sera diluted 1:200 in TBS laboratories, Inc.) were coated with poly-L-lysine for one hour in 37°C and then washed three times (50 ug/ml), the antigen to be screened (2.5 ug/ml) and with 0.05% tween -20 in PBS. The microtiter wells poly-L-glutamate (50 ug/ml). The sera were diluted were then incubated at 37°C for one hour with with 2% bovine serum in tris buffer saline (BS-TBS) anti-human immunoglobulin alkaline phosphotase and used in the assay at a dilution of 1: 200. One conjugated. The reaction was continued hence hundred and fifty ml of the sera were added to the forward as described above.
AUTOANTIBODIES IN LYMPHOMA
119
while anti-Sm, and anti SSB were found in 16.7% and 14.3% respectively. Other autoantibodies could be The anti-idiotypic sera (R-anti-16/6)were prepared by detected in less than 10% of the sera. The increased monthly immunization of rabbits with monocolonal frequency of anti-ssDNA, anti-RNP and anti-Sm lupus anti-DNA antibodies, as detailed previouslyz5. autoantibodies was statistically significant as compared to controls ( p < 0.01, p e 0.05, respectively). Detection of idiotypes in sera of patients with Production of anti-idiotype antibodies
Leuk Lymphoma Downloaded from informahealthcare.com by University of Alberta on 01/14/15 For personal use only.
lymphoma
Polystyrene plates containing 96 wells (Nunc) were incubated with serum diluted in 0.05 M borate buffer for 18 hr at 4°C and then washed three times with 1% tween - 20 phosphate-buffered saline (1YO T-PBS) and PBS. Titration curves with dilutions of normal and lupus serum that extended over three orders of magnitude were carried out to select optimal dilutions for the assay27. The optimal serum dilutions were close to the midpoints of the slopes of the titration curves (1: 10,000). The anti-idiotypic serum was diluted (1:12,000 for 16/6). In 0.1% T-PBS and added to the serum-coated wells. After incubation for 2 hr at room temperature the plates were washed three times with 1% T-PBS and blocked with PBS-l% BSA for 2 hr and 150 ul of goat anti-rabbit immunoglobulin conjugated to alkaline phosphatase was added. The plates were then incubated overnight at room temperature. Determination of the bound alkaline phosphatase conjugate was detected by the addition of 150 uL p- nitrophenyl phosphate (1 mg/ml in 0.5 M NaHCO,, 2 mM MgCl,, pH 9.5, at 23°C).The optical densities were read as detailed above.
Autoantibodies in the sera of patients with non-Hodgkin’s and Hodgkin’s lymphoma
Tables 2-4 summarize the frequency of autoantibodies separately in patients with NHL and HD. It seems that patients with NHL differ from those with HD by having significantly increased titers of anti-dsDNA and a greater tendency toward anti-ssDNA antibodies. Polyspecificity of sera of patients with lymphoma
Thirty three sera of the 84 lymphoma patients were positive for at least one antigen; 20 were found to react with ssDNA, 19 with RNP, 14 with Sm, 12 with SSB, 8 with Poly (G),7 with SSA, 6 with cardiolipin, 4 with Poly (I), 1 with histones and none with the 16/6 Id. Among those 33 sera; 9 were found to react with one antigen, 6 with 2 antigens, 7 with 3 antigens, 4 with 4 antigens, 4 with 5 antigens and three with 6,7 and 8 antigens, respectively.
DISCUSSION
Autoimmune diseases and cancer are being diagnosed with increasing frequency, and there are many reports of an association between immune-mediated diseases ELISA values above the mean + 2 SD of the normal and neoplasia6*8*’6. In addition to the conventional sera were considered positive, an index shown autoantibodies such as anti-ssDNA and antipreviously to differentiate “normal” values from high his tone^^^.^^, novel autoantibodies were reported to valuesz7.The percentage of the high titer sera samples be associated with new clinical syndromes3’. was compared to the normal controls by the In contrast to previous reports, we have recently chi-square test. described an equal prevalence of a wide spectrum of anti-nuclear autoantibodies in the sera of 164 patients with various solid tumors as compared to a control RESULTS group, matched for both age and sex17. The increased incidence of autoantibodies in the sera of patients with Detection of autoantibodies in the sera of patients solid tumors reported by others was probably due to with lymphoma the older age of the patients with malignancies3’, The binding of patients and control sera to different rather than to the presence of the tumor. antigens is shown in Figures la and l b and Table 1. In the present study we extended the analysis to It can be seen that anti-ssDNA antibodies were found include patients with non-Hodgkin’s and Hodgkin’s in 23.8% of the patients with lymphoma (including lymphoma, employing the ELISA method to detect a HD and NHL). In 19.5% anti-RNP was detected diverse range of autoantibodies. In contrast to our Statistical analysis
0
0
Leuk Lymphoma Downloaded from informahealthcare.com by University of Alberta on 01/14/15 For personal use only.
t
! .
f 1 1 3 E
0.0 xd
Anti Sm
AntiRNP AntiSSA AntiSSB Anti'WkId
...
60
. .. ib t
-
0
40
B a
-
. . :o
0
n 0
: 0
10(
i
0
a
.
.
i.
3.
T 0
i O
n
B
1 :
Figure l(e), (b) The frequency of antinuclear antibodies in the sera of patients with lymphoma compared to normal controls (NC) matched for age and sex. (anti-1616 id: anti-common anti-DNA idiotype-16/6).
AUTOANTIBODIES IN LYMPHOMA
Table 1 Frequency of auto-antibodies detected among 84 patients with lymphoma and 46 age adjusted normal-controls Autoantibody to
ssDNA dsDNA POIY (1) Poly (GI
Sm RNP
Leuk Lymphoma Downloaded from informahealthcare.com by University of Alberta on 01/14/15 For personal use only.
SS/A
SS/B Cardiolipin Histones 1616 Id
Lymphomu pat ient s
Normal controls
n = 84 20 (23.8%) 6 (7.I yo) 4 (4.8%) 8 (9.5%) 14 (16.7%) 16 (19.5%) 7 (8.3%) 12 (14.3%) 5 (6%) 1 (1.2%) 0 (0%)
n = 46 2 (4.3%) 4 (8.7%) 4 (8.7%) 4 (8.7%) 1 (2.2%) 2 (4.3%) 5 (10.9%) 3 (6.5%) 3 (6.5%) 3 (6.5%) 1 (2.2%)
