Rheumatology and Rehabilitation, 1976, 15, 45
ORIGINAL PAPER
SEROLOGICAL CHANGES IN PROGRESSIVE SYSTEMIC SCLEROSIS BY P. DAVIS AND M. I. V. JAYSON Department of Medicine, University of Bristol and Royal National Hospital for Rheumatic Diseases, Bath
SEROLOGICAL changes and particularly the presence of antinuclear antibodies occur in some patients with progressive systemic sclerosis. The incidence of such changes varies between 27 % and 78 % (Mandema et al, 1961; Beck et al., 1963) suggesting that immunological mechanisms could play some part in the aetiology of this disease. This study is directed at reviewing the serological changes in patients with scleroderma seen at a special clinic and determining the nature of the antinuclear antibodies of this disease.
CASES Of 37 patients with scleroderma, 32 were females and five were males. Thirty-one patients had diffuse skin involvement most marked in the hands, with a high incidence of Raynaud's phenomenon, acrosclerosis, oesophageal involvement and systemic features and were classified as typical progressive systemic sclerosis (PSS). Six patients had focal scleroderma, mainly discrete lesions on the trunk, and were classified as morphoea. All patients on skin biopsy had the histological changes of scleroderma. Of 25 skin biopsies that were examined, excess cross-link patterns were found in 18, indicating the proliferation of new collagen (Herbert et al., 1974). Three patients died, one with gross disease and terminal inhalation pneumonia and two with renal glomerulo-arteriolar sclerosis. None of the other patients had evidence of renal disease as detected by blood urea, creatinine clearance, proteinuria or hypertension. Three patients had abnormal liver function tests and one of these had chronic active hepatitis (CAH) on liver biopsy. Two patients had clinical evidence of Sjttgren's syndrome and seven pulmonary fibrosis. The clinical features were documented in each patient and the plasma viscosity and serum proteins were determined. Sera were screened using the standard laboratory tests for rheumatoid factor by the Rose Waaler and latex techniques, lupus erythematosus (LE) cells, immunofluorescence for antinuclear, antithyroid, antigastric parietal cells, Reprint requests should be sent to M. I. V. Jayson, Bristol Royal Infirmary, Bristol BS2, 8HW Accepted for publication November 1975. 45
Downloaded from http://rheumatology.oxfordjournals.org/ at Carleton University on July 15, 2015
SUMMARY Sera from 37 patients with scleroderma were studied for the presence of auto-antibodies. Rheumatoid factors and antibodies to smooth muscle and thyroid were seen in some patients. Ten of 31 patients (32 %) had antibodies to nuclear antigens. They were not related to the extent or severity of disease but were often associated with other complications or coincidental diseases. These serological changes only occurred in the patients with progressive systemic sclerosis and did not occur in morphoea. Antibodies to double-stranded DNA were found in only one case, and neither clinical nor serological overlap with systemic lupus erythematosus were seen in this group of patients.
46
RHEUMATOLOGY AND REHABILITATION VOL. XV NO. 1
antismooth muscle, and antimitochondrial antibodies. Serum complement and immunoglobulins were measured by radial immunodiffusion techniques. Antibodies to doublestranded (native) DNA were measured by the Fair ammonium sulphate precipitation test (Wold et aJ., 1968).
Serum proteins Twenty-three of 29 patients had normal serum albumin and serum globulin. Six patients had hyperglobuUnaemia, and two of these had hypoalbuminaemia. In only one
1:512
- 1:840
1:266 -
•
1:128 -
: : :
--1 : 3 2 0
•
•
.
.
-. 1:160
;
1:64
•
•
;
1:32
- 1:80
- 1:40
•
1:16 -
- 1:20
1:8
•
•
•
- 1:10
Neg
Neg Rheumatoid factor
A.N.A.
Smooth muscle A.B.
Thyroid A.B.
Fio. 1.—Auto-antibody titres in patients with sclerodcrma.
Downloaded from http://rheumatology.oxfordjournals.org/ at Carleton University on July 15, 2015
RESULTS Plasma viscosity The plasma viscosity, a nonspecific indication of inflammatory disease similar to the erythrocyte sedimentation rate, was elevated in 14 of 28 patients (50 %). The changes were not related to clinical or biochemical findings nor to the plasma proteins.
DAVIS AND JAYSON: SEROLOGICAL CHANGES IN PSS
47
of these patients were the albumin and globulin markedly abnormal, this being the patient with chronic active hepatitis (albumin 2.8 g/100 ml, globulin 5.4 g/100 ml). There was no consistent abnormality in immunoglobulin levels in these patients. Nine of 14 patients had raised IgG levels, two had raised IgA levels and six raised IgM levels. Significant abnormalities of immunoglobulin levels were only seen in two of the patients with liver disease.
120 -
i
•
i
I
i•
f
r • 80 -
( /
•
f f i f '
«
30
i '
i
' / /
•
/
f /
/
»
•
. :
i
it: ONA
Binding
/
• i
Serum
Fro. 2.—Serum DNA binding percentage and C3 levels in mg/100 ml in patients with scleroderma.
Downloaded from http://rheumatology.oxfordjournals.org/ at Carleton University on July 15, 2015
Rheumatoid factor and auto-antibodies (Fig. 1) Twenty-nine of 37 patients had a negative latex test. One had a positive latex and negative Rose Waaler test. Seven patients had positive latex tests with Rose Waaler
48
RHEUMATOLOGY AND REHABILITATION VOL. XV NO. 1
titres of 1:16 (borderline), 1:32 (2), 1:64 (2), 1:512 and 1:1024. One of these patients had classical rheumatoid arthritis. In contrast, ten of 31 patients had a positive antinuclear antibody (ANA) titre. Of these, the highest level, 1:32O, was seen in the patient with active chronic hepatitis. Two patients with ANA in a titre of 1:160 had SjSgren's syndrome. Two patients with ANA+1:160 had abnormal liver function tests and one ANA +1:40 had a nonspecific proctocolitis. Four had positive ANA tests but no clinical evidence of disease other than cutaneous PSS. Three patients had smooth muscle AB and five had thyroid antibodies. No patient with thyroid antibodies had other clinical or laboratory evidence of thyroid disease. In no case of morphoea was a positive ANA test obtained.
DISCUSSION Although the aetiology of PSS is unknown, recent studies have improved our understanding of some of the pathogenetic mechanisms involved. Herbert and her colleagues (1974) recently showed changes in the chemical structure of adult dermal collagen in progressive systemic sclerosis and these represent active new collagen proliferation. The cause of new collagen proliferation is not known. LeRoy, McGuire and Chen (1974) showed that isolated PSS fibroblasts produce more collagen than control fibroblasts and Jayson (unpublished observations) has failed to find serological factors that could stimulate collagen synthesis. In animal models, hypoxia and vasoconstriction have produced similar histological changes to those in scleroderma (Harris and Robinson, 1974) and could play some part in human disease. Renal failure in PSS is due to arteriolar obstruction with gross proliferation of collagen in the intima. These changes were responsible for the death of two patients in this series. The extent to which such changes can produce the dermal manifestations is not known. Skin biopsies from patients with early PSS contain a mild lymphocytic infiltrate. This may be relevant as lymphokines are known to stimulate fibroblast in tissue culture to produce new collagen (Johnson and Ziff, 1974). The involvement of lymphocytes in cell-mediated immunological reactions in other connective-tissue diseases has suggested a similar role in PSS although there is little evidence for this suggestion. Changes in humoral immunity are better documented. A number of studies (McGiven et al., 1968, Beck et al, 1963, Mandema et al., 1961, Rothfield and Rodnan, 1968) have reported that sera from patients with PSS contain a high incidence of both organ- and non-organspecific antibodies. In particular antinuclear antibodies and rheumatoid factor (Rh.F) are common. Dubois (1974) showed that in PSS patients the occurrence of LE cells can be related to systemic lupus erythematosus-like manifestations such as pleurisy or pericarditis. Interest in antinuclear antibodies has increased recently with the development of accurate techniques to detect antibodies against specific nuclear antigens such as DNA. Antibodies to native DNA have a high degree of specificity for 'lupus' syndromes. In
Downloaded from http://rheumatology.oxfordjournals.org/ at Carleton University on July 15, 2015
Antibodies to polynucleotides and serum complement levels (Fig. 2) No patient had LE cells. Antibodies to double-stranded (native) DNA were found at a significant level only in the patient with CAH (48 %). Antibodies to double-stranded DNA were normal in 31 other patients. Serum complement levels were significantly depressed at less than 70 mg/100 ml in four patients of whom three had positive titres of ANA. In one, the patient with CAH, complement breakdown products were also detected. One of the other two had Sjdgren's syndrome.
DAVIS AND JAYSON: SEROLOGICAL CHANGES IN PSS
49
REFERENCES
J. S., ANDERSON, J. R., GRAY, K. G. and ROWEIX, N. R. (1963) "Antinuclear and Precipitating Auto-antibodies in Progressive Systemic Sclerosis". Lancet, 4,1188. DAVIS, P. and READ, A. E. (1975) "Anti-bodies to d.s. (native) DNA in Chronic Hepatitis". Gut. In the press. DUBOIS, E. L. (1974) "Relationship between SLE, PSS, and Mixed Connective Tissue Disease". In: Lupus Erythematosus, ed.: E. L. Dubois. University of Southern California Press, p. 477. HANSON, V., DREXLER, E. and KORNREICH, H. (1970) "DNA Anti-bodies in Childhood Scleroderma". Arthritis Rheum., 13,798. HARRIS, E. D. and ROBINSON, M. S. (1974) "Increased Collagen Synthesis by Rat Tail Tendon Cells in Response to Ergotamine: A Possible Model for Scleroderma". Proc. VI Pan Am. Congr. Rheum. Dis., p. 149. HERBERT, C. M., LINDBERG, K. A,, JAYSON, M. I. V. and BAILEY, A. J. (1974) "Biosynthesis and Maturation of Skin Collagen in Scleroderma and Effect of D-PeniciHamine". Lancet, i, 187. JOHNSON, R. L. and ZTFF, M. (1974) "Lytnphokine Stimulation of Collagen Synthesis". Proc. VIPan Am. Congr. Rheum. Dis., 53. LEROY, E. C , MCGUIRE, M. and CHEN, N. (1974) "Increased Collagen Synthesis by Scleroderma Skin Fibroblasts in vitro". J. Clin. Invest., 54,880. MANDEMA, E., POIXAK, V. E., KARK, R. M. and REZAIAN, J. (1961) "Quantitative Observations on Anti-nuclear Factors in Systemic Lupus Erythematosus". / . Lab. Clin. Med., 58, 337. BECK,
Downloaded from http://rheumatology.oxfordjournals.org/ at Carleton University on July 15, 2015
general, systemic lupus erythematosus (SLE) and progressive systemic sclerosis are clinically distinct, although Sharp et al. (1972) have described a 'mixed connective tissue' disease with clinical features of both. In this disease there appears a specific antinuclear antibody to extractable nuclear antigen (ENA) which contains both RNA and nucleoprotein. Some of the patients described by Sharp had antibodies to native DNA suggesting a predominantly lupus-like illness. Our study has confirmed that some patients with PSS have high titres of auto-antibodies including ANA, Rh.F and thyroid antibodies. In a previous study (Rothfield and Rodnan, 1968) no correlation was found between serological changes and clinical features of the disease. This was not so in the present series in which ANA were particularly seen in relation to other problems. Three of the patients with the highest positive ANA titres had abnormalities of liver function and one had biopsy proven chronic active hepatitis. Two other patients had SjSgren's syndrome and one a nonspecific proctocolitis. This study was unsuccessful in elucidating the nature of the ANA in PSS. Only the patient with CAH had elevated DNA binding and this is now a recognized feature of that disease (Davis and Read, 1975). An association between CAH and PSS is recognized (Morris, Htut and Read, 1972). In contrast with our observations, Hanson, Drexler and Kornreich (1970) found antibodies to DNA in seven of eighteen children with focal scleroderma. Significant suppression of serum complement levels was seen in only four patients one of whom had SjSgren's syndrome, and another CAH. In the patients with renal involvement, serum complement was not lowered and antinuclear antibodies were not detected. Histology confirmed the presence of renal arteriolar glomerulo-sclerosis in the two patients who died and immune complex deposition was not seen. In the previous studies reported, there is some variability in the incidence of serological abnormalities in PSS. Our study confirms some of these observations but suggests that changes in serology are not a predominant feature of the disease and that when they occur they are often associated with coincidental or related diseases. Clinical and serological overlap with SLE, producing mixed connective tissue disease, is uncommon. These results do not suggest that immunological factors play a major role in the aetiology of PSS.
50
RHEUMATOLOGY AND REHABILITATION VOL. XV NO. 1
McGrvEN, A. R., BOER, W. G. R. M., BARNETT, A. J. and COVENTRY, D. A. (1968) "Autoantibodies in Scleroderma". Med. J. Aust., 2,533. MORRIS, J. S., HTUT, T. and READ, A. E. (1972) "Scleroderma and Portal Hypertension". Ann. Rheum. Dis.,31,316. RoTHFiELD, N. R. and RODNAN, G. P. (1968) "Serum Anti-nuclear Antibodies in Progressive Systemic Sclerosis". Arthritis Rheum., 11, 607. SHARP, G. G, IRWIN, W. S., TAN, E. M., GOULD, R G. and HOLMAN, H. R (1972) "Mixed Connective Tissue Disease^—^An Apparently Distinct Rheumatic Disease Syndrome Associated with Specific Antibody to an Extractable Nuclear Antigen (ENA)". Am. J. Med., 52,148. WOLD, E. T., YOUNO, F. E., TAN, E. and FARR, S. (1968) "DNA Antibody: An Effort to Detect
its Primary Interaction with DNA". Science, 161,806. Downloaded from http://rheumatology.oxfordjournals.org/ at Carleton University on July 15, 2015
ORIGINAL PAPER
SEROLOGICAL CHANGES IN PROGRESSIVE SYSTEMIC SCLEROSIS BY P. DAVIS AND M. I. V. JAYSON Department of Medicine, University of Bristol and Royal National Hospital for Rheumatic Diseases, Bath
SEROLOGICAL changes and particularly the presence of antinuclear antibodies occur in some patients with progressive systemic sclerosis. The incidence of such changes varies between 27 % and 78 % (Mandema et al, 1961; Beck et al., 1963) suggesting that immunological mechanisms could play some part in the aetiology of this disease. This study is directed at reviewing the serological changes in patients with scleroderma seen at a special clinic and determining the nature of the antinuclear antibodies of this disease.
CASES Of 37 patients with scleroderma, 32 were females and five were males. Thirty-one patients had diffuse skin involvement most marked in the hands, with a high incidence of Raynaud's phenomenon, acrosclerosis, oesophageal involvement and systemic features and were classified as typical progressive systemic sclerosis (PSS). Six patients had focal scleroderma, mainly discrete lesions on the trunk, and were classified as morphoea. All patients on skin biopsy had the histological changes of scleroderma. Of 25 skin biopsies that were examined, excess cross-link patterns were found in 18, indicating the proliferation of new collagen (Herbert et al., 1974). Three patients died, one with gross disease and terminal inhalation pneumonia and two with renal glomerulo-arteriolar sclerosis. None of the other patients had evidence of renal disease as detected by blood urea, creatinine clearance, proteinuria or hypertension. Three patients had abnormal liver function tests and one of these had chronic active hepatitis (CAH) on liver biopsy. Two patients had clinical evidence of Sjttgren's syndrome and seven pulmonary fibrosis. The clinical features were documented in each patient and the plasma viscosity and serum proteins were determined. Sera were screened using the standard laboratory tests for rheumatoid factor by the Rose Waaler and latex techniques, lupus erythematosus (LE) cells, immunofluorescence for antinuclear, antithyroid, antigastric parietal cells, Reprint requests should be sent to M. I. V. Jayson, Bristol Royal Infirmary, Bristol BS2, 8HW Accepted for publication November 1975. 45
Downloaded from http://rheumatology.oxfordjournals.org/ at Carleton University on July 15, 2015
SUMMARY Sera from 37 patients with scleroderma were studied for the presence of auto-antibodies. Rheumatoid factors and antibodies to smooth muscle and thyroid were seen in some patients. Ten of 31 patients (32 %) had antibodies to nuclear antigens. They were not related to the extent or severity of disease but were often associated with other complications or coincidental diseases. These serological changes only occurred in the patients with progressive systemic sclerosis and did not occur in morphoea. Antibodies to double-stranded DNA were found in only one case, and neither clinical nor serological overlap with systemic lupus erythematosus were seen in this group of patients.
46
RHEUMATOLOGY AND REHABILITATION VOL. XV NO. 1
antismooth muscle, and antimitochondrial antibodies. Serum complement and immunoglobulins were measured by radial immunodiffusion techniques. Antibodies to doublestranded (native) DNA were measured by the Fair ammonium sulphate precipitation test (Wold et aJ., 1968).
Serum proteins Twenty-three of 29 patients had normal serum albumin and serum globulin. Six patients had hyperglobuUnaemia, and two of these had hypoalbuminaemia. In only one
1:512
- 1:840
1:266 -
•
1:128 -
: : :
--1 : 3 2 0
•
•
.
.
-. 1:160
;
1:64
•
•
;
1:32
- 1:80
- 1:40
•
1:16 -
- 1:20
1:8
•
•
•
- 1:10
Neg
Neg Rheumatoid factor
A.N.A.
Smooth muscle A.B.
Thyroid A.B.
Fio. 1.—Auto-antibody titres in patients with sclerodcrma.
Downloaded from http://rheumatology.oxfordjournals.org/ at Carleton University on July 15, 2015
RESULTS Plasma viscosity The plasma viscosity, a nonspecific indication of inflammatory disease similar to the erythrocyte sedimentation rate, was elevated in 14 of 28 patients (50 %). The changes were not related to clinical or biochemical findings nor to the plasma proteins.
DAVIS AND JAYSON: SEROLOGICAL CHANGES IN PSS
47
of these patients were the albumin and globulin markedly abnormal, this being the patient with chronic active hepatitis (albumin 2.8 g/100 ml, globulin 5.4 g/100 ml). There was no consistent abnormality in immunoglobulin levels in these patients. Nine of 14 patients had raised IgG levels, two had raised IgA levels and six raised IgM levels. Significant abnormalities of immunoglobulin levels were only seen in two of the patients with liver disease.
120 -
i
•
i
I
i•
f
r • 80 -
( /
•
f f i f '
«
30
i '
i
' / /
•
/
f /
/
»
•
. :
i
it: ONA
Binding
/
• i
Serum
Fro. 2.—Serum DNA binding percentage and C3 levels in mg/100 ml in patients with scleroderma.
Downloaded from http://rheumatology.oxfordjournals.org/ at Carleton University on July 15, 2015
Rheumatoid factor and auto-antibodies (Fig. 1) Twenty-nine of 37 patients had a negative latex test. One had a positive latex and negative Rose Waaler test. Seven patients had positive latex tests with Rose Waaler
48
RHEUMATOLOGY AND REHABILITATION VOL. XV NO. 1
titres of 1:16 (borderline), 1:32 (2), 1:64 (2), 1:512 and 1:1024. One of these patients had classical rheumatoid arthritis. In contrast, ten of 31 patients had a positive antinuclear antibody (ANA) titre. Of these, the highest level, 1:32O, was seen in the patient with active chronic hepatitis. Two patients with ANA in a titre of 1:160 had SjSgren's syndrome. Two patients with ANA+1:160 had abnormal liver function tests and one ANA +1:40 had a nonspecific proctocolitis. Four had positive ANA tests but no clinical evidence of disease other than cutaneous PSS. Three patients had smooth muscle AB and five had thyroid antibodies. No patient with thyroid antibodies had other clinical or laboratory evidence of thyroid disease. In no case of morphoea was a positive ANA test obtained.
DISCUSSION Although the aetiology of PSS is unknown, recent studies have improved our understanding of some of the pathogenetic mechanisms involved. Herbert and her colleagues (1974) recently showed changes in the chemical structure of adult dermal collagen in progressive systemic sclerosis and these represent active new collagen proliferation. The cause of new collagen proliferation is not known. LeRoy, McGuire and Chen (1974) showed that isolated PSS fibroblasts produce more collagen than control fibroblasts and Jayson (unpublished observations) has failed to find serological factors that could stimulate collagen synthesis. In animal models, hypoxia and vasoconstriction have produced similar histological changes to those in scleroderma (Harris and Robinson, 1974) and could play some part in human disease. Renal failure in PSS is due to arteriolar obstruction with gross proliferation of collagen in the intima. These changes were responsible for the death of two patients in this series. The extent to which such changes can produce the dermal manifestations is not known. Skin biopsies from patients with early PSS contain a mild lymphocytic infiltrate. This may be relevant as lymphokines are known to stimulate fibroblast in tissue culture to produce new collagen (Johnson and Ziff, 1974). The involvement of lymphocytes in cell-mediated immunological reactions in other connective-tissue diseases has suggested a similar role in PSS although there is little evidence for this suggestion. Changes in humoral immunity are better documented. A number of studies (McGiven et al., 1968, Beck et al, 1963, Mandema et al., 1961, Rothfield and Rodnan, 1968) have reported that sera from patients with PSS contain a high incidence of both organ- and non-organspecific antibodies. In particular antinuclear antibodies and rheumatoid factor (Rh.F) are common. Dubois (1974) showed that in PSS patients the occurrence of LE cells can be related to systemic lupus erythematosus-like manifestations such as pleurisy or pericarditis. Interest in antinuclear antibodies has increased recently with the development of accurate techniques to detect antibodies against specific nuclear antigens such as DNA. Antibodies to native DNA have a high degree of specificity for 'lupus' syndromes. In
Downloaded from http://rheumatology.oxfordjournals.org/ at Carleton University on July 15, 2015
Antibodies to polynucleotides and serum complement levels (Fig. 2) No patient had LE cells. Antibodies to double-stranded (native) DNA were found at a significant level only in the patient with CAH (48 %). Antibodies to double-stranded DNA were normal in 31 other patients. Serum complement levels were significantly depressed at less than 70 mg/100 ml in four patients of whom three had positive titres of ANA. In one, the patient with CAH, complement breakdown products were also detected. One of the other two had Sjdgren's syndrome.
DAVIS AND JAYSON: SEROLOGICAL CHANGES IN PSS
49
REFERENCES
J. S., ANDERSON, J. R., GRAY, K. G. and ROWEIX, N. R. (1963) "Antinuclear and Precipitating Auto-antibodies in Progressive Systemic Sclerosis". Lancet, 4,1188. DAVIS, P. and READ, A. E. (1975) "Anti-bodies to d.s. (native) DNA in Chronic Hepatitis". Gut. In the press. DUBOIS, E. L. (1974) "Relationship between SLE, PSS, and Mixed Connective Tissue Disease". In: Lupus Erythematosus, ed.: E. L. Dubois. University of Southern California Press, p. 477. HANSON, V., DREXLER, E. and KORNREICH, H. (1970) "DNA Anti-bodies in Childhood Scleroderma". Arthritis Rheum., 13,798. HARRIS, E. D. and ROBINSON, M. S. (1974) "Increased Collagen Synthesis by Rat Tail Tendon Cells in Response to Ergotamine: A Possible Model for Scleroderma". Proc. VI Pan Am. Congr. Rheum. Dis., p. 149. HERBERT, C. M., LINDBERG, K. A,, JAYSON, M. I. V. and BAILEY, A. J. (1974) "Biosynthesis and Maturation of Skin Collagen in Scleroderma and Effect of D-PeniciHamine". Lancet, i, 187. JOHNSON, R. L. and ZTFF, M. (1974) "Lytnphokine Stimulation of Collagen Synthesis". Proc. VIPan Am. Congr. Rheum. Dis., 53. LEROY, E. C , MCGUIRE, M. and CHEN, N. (1974) "Increased Collagen Synthesis by Scleroderma Skin Fibroblasts in vitro". J. Clin. Invest., 54,880. MANDEMA, E., POIXAK, V. E., KARK, R. M. and REZAIAN, J. (1961) "Quantitative Observations on Anti-nuclear Factors in Systemic Lupus Erythematosus". / . Lab. Clin. Med., 58, 337. BECK,
Downloaded from http://rheumatology.oxfordjournals.org/ at Carleton University on July 15, 2015
general, systemic lupus erythematosus (SLE) and progressive systemic sclerosis are clinically distinct, although Sharp et al. (1972) have described a 'mixed connective tissue' disease with clinical features of both. In this disease there appears a specific antinuclear antibody to extractable nuclear antigen (ENA) which contains both RNA and nucleoprotein. Some of the patients described by Sharp had antibodies to native DNA suggesting a predominantly lupus-like illness. Our study has confirmed that some patients with PSS have high titres of auto-antibodies including ANA, Rh.F and thyroid antibodies. In a previous study (Rothfield and Rodnan, 1968) no correlation was found between serological changes and clinical features of the disease. This was not so in the present series in which ANA were particularly seen in relation to other problems. Three of the patients with the highest positive ANA titres had abnormalities of liver function and one had biopsy proven chronic active hepatitis. Two other patients had SjSgren's syndrome and one a nonspecific proctocolitis. This study was unsuccessful in elucidating the nature of the ANA in PSS. Only the patient with CAH had elevated DNA binding and this is now a recognized feature of that disease (Davis and Read, 1975). An association between CAH and PSS is recognized (Morris, Htut and Read, 1972). In contrast with our observations, Hanson, Drexler and Kornreich (1970) found antibodies to DNA in seven of eighteen children with focal scleroderma. Significant suppression of serum complement levels was seen in only four patients one of whom had SjSgren's syndrome, and another CAH. In the patients with renal involvement, serum complement was not lowered and antinuclear antibodies were not detected. Histology confirmed the presence of renal arteriolar glomerulo-sclerosis in the two patients who died and immune complex deposition was not seen. In the previous studies reported, there is some variability in the incidence of serological abnormalities in PSS. Our study confirms some of these observations but suggests that changes in serology are not a predominant feature of the disease and that when they occur they are often associated with coincidental or related diseases. Clinical and serological overlap with SLE, producing mixed connective tissue disease, is uncommon. These results do not suggest that immunological factors play a major role in the aetiology of PSS.
50
RHEUMATOLOGY AND REHABILITATION VOL. XV NO. 1
McGrvEN, A. R., BOER, W. G. R. M., BARNETT, A. J. and COVENTRY, D. A. (1968) "Autoantibodies in Scleroderma". Med. J. Aust., 2,533. MORRIS, J. S., HTUT, T. and READ, A. E. (1972) "Scleroderma and Portal Hypertension". Ann. Rheum. Dis.,31,316. RoTHFiELD, N. R. and RODNAN, G. P. (1968) "Serum Anti-nuclear Antibodies in Progressive Systemic Sclerosis". Arthritis Rheum., 11, 607. SHARP, G. G, IRWIN, W. S., TAN, E. M., GOULD, R G. and HOLMAN, H. R (1972) "Mixed Connective Tissue Disease^—^An Apparently Distinct Rheumatic Disease Syndrome Associated with Specific Antibody to an Extractable Nuclear Antigen (ENA)". Am. J. Med., 52,148. WOLD, E. T., YOUNO, F. E., TAN, E. and FARR, S. (1968) "DNA Antibody: An Effort to Detect
its Primary Interaction with DNA". Science, 161,806. Downloaded from http://rheumatology.oxfordjournals.org/ at Carleton University on July 15, 2015
