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Springer Semin.Immnnopathol.

(1981)4:253-273 Springer Seminars


in Immunopathology
© Springer-Verlag 1981

Ro (SSA) and La (SSB) Antibodies


Elaine L. Alexander and Thomas T. Provost

Departmentsof Medicineand Dermatology,JohnsHopkinsSchoolof Medicine,Baltimore,Maryland


21239, USA

Summary

This review traces the historical development of information regarding the Ro (SSA)
and La (SSB) autoantibody systems over the past twenty years. Clinical and
serologic findings are integrated with fundamental observations in this rapidly
expanding area of research. Retrospective analysis of the physicochemical proper-
ties of the antigens and the cellular staining characteristics of antibodies to these
antigens suggest that SjD and Ro and SSA, as well as SjT and La, SSB, and Ha
antigens probably are similar macromolecules. The immunologic identity of Ro
with SSA and La with SSB and Ha has been established previously. Antibodies to
these antigens are directed against macromolecules containing small RNA
nucleotides.
Antibodies to the Ro (SSA)-La(SSB) antigen system commonly are detected in
the sera of patients with systemic lupus erythematosus and Sj/Sgren's syndrome and
appear to be of diagnostic significance. These antibodies occur in up to one quarter
of patients with systemic lupus erythematosus (SLE) without the sicca complex, but
also in patients with ANA negative SLE who have a prominent photosensitive
dermatitis and may have serious renal disease, subacute cutaneous SLE, and in
infants and mothers of infants with neonatal SLE. Thus, these antibody systems
form a serologic link between many unusual connective tissue diseases and systemic
SLE.
Antibodies to Ro (SSA)-La(SSB) are associated not only with Sj6gren's
syndrome occurring alone, but also with Sj6gren's syndrome occurring in the
setting of other connective tissue diseases including SLE and rheumatoid arthritis.
Anemia, leukopenia, and thromboeytopenia, as well as hyperglobulinemia and the

Supported by National Institutes of Health grant 5R01-AM-25650-03 and Research Career


DevelopmentAward 5-KO-4-AM-00524-02

0344-4325/81/0004/0253/$ 04.20
254 Elaine L. Alexander and Thomas T. Provost

presence of rheumatoid factor, cryoglobulins, and antibodies to nuclear antigens are


associated significantly with Ro positivity in Sj6gren's syndrome patients. There is a
striking association of vasculitis in the clinical setting of Sj6gren's syndrome with
the presence of antibodies to Ro (SSA). In addition to peripheral nerve involvement,
unusual central nervous system manifestations as well as myositis occur in these
Ro(SSA) positive Sj6gren's syndrome patients. Deposition of immunoglobulin and
complement within vessel walls of kidney and muscle from Ro positive patients with
Sj6gren's syndrome suggests a possible role for immune complex deposition in the
pathogenesis of the vasculitis.

Introduction

This paper is designed to review recent advances in our knowledge of the Ro(SSA)
and La(SSB) autoantibody systems and to emphasize their clinical importance in
the evaluation of patients with connective tissue disease. Much of the data presented
in this review has been recently, or is about to be published. Like any new area of
research, some controversy presently surrounds the field. As will be demonstrated,
this controversy revolves around several observations. First, the antigens to which
these autoantibodies are directed may have different physicochemical properties
depending upon the source of tissue from which they are obtained. Antibodies to
these antigens may or may not be detected by routine immunofluorescence
techniques depending upon the substrate employed. Finally, there are some
conflicting data regarding the exact cellular localization of the antigens depending
on the source of tissue. Despite these areas of controversy, antibodies to Ro(SSA)
and La(SSB) have been proven to be valuable clinical diagnostic tools.
Although autoantibodies to cellular macromolecules recently have gained much
recognition in the evaluation of connective tissue disease, such antibodies were
probably first recognized over twenty years ago. In the late 1950's, several
investigators demonstrated the presence of complement fixing and precipitating
antibodies in sera from patients with connective tissue disorders. Gajdusek [20, 30],
in 1958, first described the presence of complement fixing antibodies to human and
animal tissues in the sera of patients with SLE and chronic hepatitis. Subsequently,
Asherson [8] demonstrated complement fixing anticytoplasmic antibodies in SLE
and other connective tissue patients.
Simultaneously, other investigators were searching for the presence of autoanti-
bodies in the sera of patients with Sj/Sgren's syndrome [7, 10, 11]. Jones [21]
employed tissue extracts of salivary and lacrimal glands to detect precipitating
autoantibodies in some Sj6gren's syndrome patients. In 1961, Anderson et al. [9]
described precipitating autoantibodies in 31% (9/29) of patients with Sj/Sgren's
syndrome. These antibodies reacted with extracts prepared from a variety of human
and animal tissue. Two distinct autoantibodies were demonstrated and were
designated SjD (Sj6gren's syndrome, reference serum from patient DON) and SiT
(Sj6gren's syndrome, reference serum from patient TRA). The physicochemical
properties of these antigens are summarized in Table 1.
Sera containing SjD antibodies (employing indirect immunofluorescence tech-
niques using heterologous liver as a substrate) demonstrated predominantly