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Resolution of the identity of certain antigen-antibody systems in systemic lupus erythematosus and sjgren's syndromeAn interlaboratory collaboration.

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16. Marston A, Jones E W Elastofibroma dorsi. Br J Surg 52
17. Enjoli M,Kikuchi J: Elastofibroma dorsi. Acta Pathol Jap
18 (2):239-244, 1968
18. Mackenzi DH, Wilson JF, Cooke KB: Elastofibroma. J
Clin Pathol21:470475, 1968
19. Mathur BBL, Dalal BJ: Elastofibroma-report of a case.
Indian J Pathol Bacteriol 17 (4):234-236, 1976
20. Constanzi G, Eusebi V Elastofibroma dorsi. Tumori
5739-352, 1971
21. Gonzalez-Crussi F, Subash R, Moloney R, Kipkie G:
Elastofibroma dorsi. Can Med Assoc J 100:374-380, 1969
22. Clark RM, Fulton AP: Elastofibroma. Can Med Assoc J
98~871-874, 1968
23. Flaiig RD, Fry PJ: Elastofibroma dorsi. J Bone Joint Surg
49-A (7):1431-1434, 1967
24. Peters JL, Fisher CS: Elastofibroma. Case report and literature review. J Thor Cardiovasc Surg 75 (6):83&838,
25. Delvaux TC, Lester J P Elastofibroma dorsi. Am J Clin
Path0143 (1):72-73, 1965
26. Freilich JK, Bendix RM: Elastofibroma, a newly reported
type of tumor. Geriatrics 24 (7):6547, 1969
27. Harry RD, Kruger RL, McLaughlin CW: Elastofibroma:
an unusual soft tissue tumor simulating sarcoma. Am J
Surg 125 (6):713-714, 1973
28. Deutsch GP: Elastofibroma dorsalis treated by radiotherapy. Br J Radio1 47:621-623, 1976
29. Leder LD: Elastofibroma. Beitr Pathol 155 (2):2W207,
30. Jgirvi OH: Elastofibroma: a disease of the aged. Geron
21:28-30, 1977
The Ouchterlony technique of double immunodiffusion, combined with some physicochemical characterization of the antigens involved, has been used to
characterize several antigen-antibody systems of importance in certain connective tissue diseases, notably systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), Sjogren’s syndrome, rheumatoid
arthritis, scleroderma, and poly- and dermatomyositis
(1-12). These systems appear to have not only considerable diagnostic significance but also importance in determining prognosis and disease course.
From the Departments of Medicine, Louisiana State University Medical School, New Orleans, Louisiana, and SUNY at Buffalo
School of Medicine, and the Veterans Administration Medical Center, Buffalo, New York.
Margaret Alspaugh, PhD; Peter Maddison, MB, MRCP.
Supported by USPHS Grant AM 10428, by funds from the
Veterans Administration,and by Grant 449-64-6184 from the Louisiana Chapter of the Arthritis Foundation.
Address reprint requests to Peter Maddison, MB, MRCP,
Veterans Administration Medical Center, 3495 Bailey Avenue, Buffalo, New York 14215.
Submitted for publication September 11, 1978; accepted in
revised form February 21,1979.
Using this technique, Reichlin and associates described two cytoplasmic proteins which were termed Ro
(4) and La (7). Antibodies to these systems were found
predominantly in serum of patients with SLE and Sjogren’s syndrome. Later Alspaugh and Tan reported the
occurrence of antibodies to two nuclear protein antigens, termed SS-A and SS-B (8,13), in extracts from B
lymphocytes in a large proportion of patients with Sjogren’s syndrome. Initially when one considered the cellular localization of antigens, susceptibility of the antigens to proteolytic and nucleolytic enzymes and heat,
and the disease specificity of the antibodies, these four
systems seemed clearly distinguishable. However, certain similarities between these systems have emerged
and this prompted an exchange of reference sera and
tissue extracts, which has resulted in demonstrating the
immunologic identity between Ro and SS-A, and La
and SS-B.
Materials and methods. Double diffusion in agar
gel and preparation of Calf thymus extract, human
spleen extract, and Wd, extract were performed as described PreviouslY (4,5,8). Both extracts and Prototype
sera were exchanged between the two laboratories.
Results. Immunodiffusion was the only technique that could confirm the immunologic identity between different sera because of the heterogeneous nature of the extracts used. Figure 1 summarizes the
results of the Ouchterlony experiments. The upper
panel demonstrates the immunologic identity between
sera containing anti-Ro and anti-SS-A by use of three
different tissue extracts as the antigen source: 1) human
Figure 1. The Ouchterlony double diffusion method demonstrating
precipitins SS-A (Ro) and SS-B (La) with various extracts: Human
spleen extract (HSE),calf thymus extract (CTE),and WU, extract.
The upper panel demonstrates a line of identity between anti-Ro (1)
and anti-SS-A (2). The middle panel demonstrates a line of identity
between anti-La (3) and anti-SS-B (4). The lower panel demonstrates
nonidentity between anti-La (SS-B) and anti-Ro (SS-A).
spleen extract (HSE), the original source of Ro (4); 2)
calf thymus extract (CTE); and 3) Wil, extract, the original source of SS-A(8). The middle panel demonstrates
the immunologic identity between anti-La and anti-SSB and the lower panel confirms the immunologic distinction between the Ro (SS-A) system and the La (SSB) system. This figure also shows that these antigens are
neither species- nor tissue-specific.
The identification of precipitating autoantibodies
to these different soluble cellular proteins has added
considerably to our knowledge of the various connective tissue diseases in which these antibodies occur.
However this area of investigation not only has been
limited by the difficulty in obtaining the antigen in a
chemically pure form but has also been complicated by
the lack of uniformity in the nomenclature of these systems. Hence, although the four systems-Ro, La, SS-A,
and SS-B-seemed clearly distinguishable, comparison
of results obtained independently in the two laboratories showed agreement between Ro and SS-A, and La
and SS-B with respect to their physicochemical properties such as their acidic nature, behavior in DEAE-cellulose chromatography, and approximate molecular
weight by the criteria of gel filtration. The disease specificity of these antibodies was also demonstrated to be
similar. Although in initial studies antibodies to SS-A
were frequently found in patients with Sjogren’s syndrome but not in those with SLE (13), a more recent examination of a large rheumatic disease population has
shown that anti-SS-A occurs in the sera of 26% of lupus
patients (14). This is similar to what was found in the
case of anti-Ro in the rheumatic disease population of
Buffalo, New York (15). The present evidence that Ro is
antigenically identical to SS-A and that La is antigenically identical to SS-B and Ha provides important simplification and understanding in this field.
Interesting discrepancies, however, are still under investigation. A constant observation is that Ro (SSA) differs in its susceptibility to trypsin, and La (SS-B)
in its susceptibility to RNase, depending on which tissue
extract is used as the antigen source. For example, although Ro in Wil, extract is susceptible to trypsin in a
concentration of 50 pg per ml after incubation at 37°C
for 2 hours, Ro in human spleen extract is not. Similarly, while RNase in a concentration of 100 pg per ml
inactivates La in calf thymus extract after incubation at
37O for 2 hours, it does not inactivate La in Wil, extract.
There is also a difference in findings with regard to the
cellular localization of these antigens. Ro and La were
considered to be of cytoplasmic origin, based on 1)
demonstration of these systems only in the cytoplasmic
fraction when cellular fractionation of fresh calf thymus
was performed in sucrose solutions, and 2) production
of cytoplasmic fluorescence of calf thymocytes by sera
immunospecific for antiRo and antila. On the other
hand nuclear localization of SS-A and SS-B was provided by similar fluorescence studies using Wil, cells as
the tissue substrate. Further investigations are therefore
in progress to resolve these particular issues.
Acknowledgments. The authors would like to express their appreciation to Dr. Moms Reichlin for his
help and advice and to Mary Johnson and Gaynell Williams of the American Federation for Negro Mairs for
their laboratory assistance.
1. Anderson JR, Gray KG, Beck JS, et a1 Precipitating autoantibodies in Sjogren’s disease. Lancet 2:456-460, 1961
2. Tan EM, Kunkel HG: Characteristics of a soluble nuclear
antigen precipitating with sera of patients with systemic
lupus erythematosus. J Immunol96:464-471, 1966
3. Tan E M An immunologic precipitin system between soluble nucleoprotein and serum antibody in systemic lupus
erythematosus. J Clin Invest 16:735-745, 1967
4. Clark G, Reichlin M,Tomasi TB: Characterization of a
soluble cytoplasmic antigen reactive with sera from patients with systemic lupus erythematosus. J Immunol
102:117-122, 1968
5. Mattioli M,Reichlin M:Characterization of a soluble nuclear ribonucleoprotein antigen reactive with SLE sera. J
I~uno1197:1281-1290, 1971
6. Sharp GC, I ~ i WS,
Tan EM, et a 1 Mixed connective
tissue disease-an apparently distinct rheumatic disease
syndrome associated with specilic antibody to an extractable nuclear antigen (ENA). Am J Med 52:148-159, 1972
7. Mattioli M,Reichlin M:Heterogeneity of RNA protein
antigens reactive with sera of patients with systemic lupus
erythematosus. Arthritis Rheum 17:421429, 1974
8. Alspaugh MA, Tan EM: Antibodies to cellular antigens in
Sjogren’s syndrome. J Clin Invest 55: 1067-1073, 1975
9. Tan EM,Rodnan G P Profile of antinuclear antibodies in
progressive systemic sclerosis (abstract). Arthritis Rheum
18:480, 1975
10. Akizuki M,Powers R, Holman HR: A soluble acidic protein of the cell nucleus which reacts with serum from patients with systemic lupus erythematosus and Sjogren’s
syndrome. J Clin Invest 59:264-272, 1977
11. Reichlin M, Mattioli M:Description of a serological reaction characteristic of polymyositis. Clin Immunol Immunopathol5: 12-20, 1976
12. Wolfe JF, Adelstein E, Sharp GC: Antinuclear antibody
with distinct specificity for polymyositis. J Clin Invest
13. Alspaugh MA, Tala1 N, Tan EM: Differentiation and
characterization of autoantibodies and their antigens in
Sjogren’s syndrome. Arthritis Rheum 19:216-222, 1976
14. Scopelitis E, Biundo JJ, Alspaugh MA: Anti-SSA antibody and other antinuclear antibodies in systemic lupus
erythematosus (abstract). Arthritis Rheum 21590, 1978
15. Maddison PJ, Reichlin M,Provost TT:Association of autoantibodies to certain cytoplasmic antigen with systemic
lupus erythematosus and other rheumatic disease (abstract). Arthritis Rheum 20:126, 1977
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