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The Precipitating Antibody to an Acidic Nuclear Protein Antigen the Jo-1 in Connective Tissue Diseases.

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604
THE PRECIPITATING ANTIBODY TO AN ACIDIC
NUCLEAR PROTEIN ANTIGEN, THE Jo-1, IN
CONNECTIVE TISSUE DISEASES
A Marker for a Subset of Polymyositis with Interstitial Pulmonary Fibrosis
SHUNJI YOSHIDA, MASASHI AKIZUKI, TSUNEYO MIMORI, HAJIME YAMAGATA,
SHINICHI INADA, and MITSUO HOMMA
The clinical significance of antibodies to the Jo-1
antigen in connective tissue diseases was studied. Clinical diagnoses of I1 patients who had anti-Jo-1 antibody
were: polymyositis 8, dermatomyositis 1, and overlap
syndrome 2 (polymyositis-systemic lupus erythematosus
1, polymyositis-scleroderma 1). All the patients who
had anti-Jo-1 antibody showed interstitial pulmonary
fibrosis, and in 2 patients antiJo-1 antibodies were
detected before the appearance of lung disease.
Identification of antinuclear antibodies with defined specificities has diagnostic and prognostic value
in connective tissue diseases (1-3). Recent studies
reveal the presence of several precipitating antibody
systems in polymyositis-dermatomyositis (PM-DM)
in which immunologic abnormalities were previously
considered to be infrequent (4-8). However, the results from several laboratories indicate that these
serologic reactions have considerable heterogeneity,
and their mutual relationships and clinical significance
remain to be clarified (8).
We have reported two distinct precipitating
From the Division of Connective Tissue Diseases, Department of Medicine, Keio University School of Medicine, Tokyo 160.
Japan.
Supported in part by a grant from the Ministry of Education, Japanese Government and the grants for promotion of young
investigators from the Keio University.
Shunji Yoshida, MD: Postdoctoral Fellow; Masashi Akizuki, MD: Associate Physician; Tsuneyo Mimori, MD: Research
Fellow; Hajime Yamagata, MD: Research Fellow; Shinichi Inada,
MD: Research Fellow; Mitsuo Homma, MD: Professor of Medicine.
Address reprint requests to Dr. Shunji Yoshida, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160. Japan.
Submitted for publication July 7, 1982; accepted in revised
form November 24, 1982.
Arthritis and Rheumatism, Vd. 26, No. 5 (May 1983)
systems in Japanese PM-DM patients (9). One of
them, termed Ku, was associated with PM-scleroderma overlap syndrome, and some of the physicochemical properties of the Ku antigen have been reported
(10). The preliminary results of analysis of another
system, the Su,by Drs. Nishikai and Reichlin showed
its identity to the Jo-1 system (Yoshida S, Nishikai M:
unpublished observations). The present work was
undertaken to clarify the immunospecificity of the Su
system and its clinical significance in connective tissue
diseases. Since the Su and Jo-1 systems are antigenically identical, the latter term has been employed.
In this communication, the disease specificity
of anti-Jo-1 antibodies in Japanese patients with connective tissue diseases, their association with activity
of muscle inflammation, and the clinical characteristics of patients with anti-Jo-1 antibodies are described.
PATIENTS AND METHODS
Patient selection. Serum samples were obtained from
324 patients with connective tissue diseases who were
followed at the Division of Connective Tissue Diseases,
Department of Medicine, Keio University Hospital, Tokyo.
The criteria for selection of patients were as follows:
patients with PM-DM had inflammatory myositis of proximal muscles and met the criteria of Medsger et al (11).
Among these, those who had typical skin lesions (heliotrope
discolorations andor erythema over the extensor surface of
joints) were classified as having derrnatomyositis (DM).
Patients with active myositis were defined as those with
elevated creatine phosphokinase (CPK) (1120 IUiliter) before steroid therapy was initiated. Patients with inactive
myositis were those who had normal CPK levels after
steroid therapy. The American Rheumatism Association
criteria were used for selecting patients with systemic lupus
erythematosus (SLE, more than 4 criteria), scleroderma,
and rheumatoid arthritis (RA, definite or classic) (12-14). In
AUTOANTIBODIES TO Jo- 1 IN POLY MYOSITIS
605
patients with overlap syndrome, 2 or more sets of the criteria
were met (10). Diagnosis of mixed connective tissue disease
(MCTD) was made according to Sharp et a1 (15,16).
The patients were grouped as follows: 32 with PMDM, 138 with SLE, 45 with scleroderma, 60 with RA, 21
with MCTD, and 28 with overlap syndrome (7 with PMSLE, 10 with PM-scleroderma, 4 with PMSLE-scleroderma, and 7 with SLE-scleroderma).
Immunologic studies. The precipitating antibodies to
the nuclear antigens were detected by the Ouchterlony
double diffusion method, as described previously (10,17).
The whole tissue extract of calf thymus (CTE), calf thymus
nuclear extract (CTNE), and rabbit thymus extract (RTE,
rabbit acetone powder, Pel-Freez Biologicals, Inc., Rogers,
AR) were used as the sources of antigens (10,171. CTE,
CTNE, and RTE were used at a protein concentration of
100, 100, and 30 mg/ml, respectively, as determined by the
Lowry method using bovine serum albumin as a standard
(18).
The serum Su from a patient with PM-SLE overlap
syndrome was used to identify the Jo-1 system. This serum
showed a single precipitin line against CTE or CTNE with a
titer of 1 : 128 and identical specificity to the precipitin line
demonstrated by the standard Jo-1 serum (kindly provided
by Dr. Nishikai) (8). The anti-Jo-1 titer was defined as the
highest serum dilution which showed a definite precipitin
line. Other specificities-nuclear ribonucleoprotein (RNP),
Sm, SS-A (Ro), SS-B (La, Ha), Mi-1, Mi-2, Scl-70 (Og), PM1, and Ku systems-were determined by reference sera as
described previously (10).
Fluorescent antinuclear antibodies (FANA), antibodies to DNA (3H-DNA binding assay), rheumatoid factor
(latex fixation test), serum IgG, IgA, IgM, and complement
levels (C3, C4) were measured by the previously described
methods (IO,l7).
Clinical studies. Patients with PM-DM were divided
into 2 groups based on the presence or absence of antibodies
to the Jo-1 antigen, and clinical characteristics were compared between the groups. Presence of pulmonary fibrosis
was determined by chest roentgenogram, and its severity
was graded according to Crystal et a1 (19,20). The statistical
analysis was performed by the Student's 1-test.
RESULTS
Figure 1. A, Identical reactivity of sera Su and Jo against calf
thymus extract (CTE). The precipitin lines developed by the two
sera show a reaction of identity against both CTE-I (prepared at
Keio) and CTE-2 (prepared by Dr. Nishikai). B, The immunologic
distinctness of the Jo-1 from the PM-I (serum We), Mi-1, and Mi-2
systems is shown. The precipitin line formed between serum Su
(diluted I :4 with phosphate buffered saline)goes through the line of
PM-I system (1:8). C, The difference of the Jo-1 system from the
Mi-1 and Mi-2 systems is demonstrated by using an extract from calf
thymocyte nuclei.
Specificities of the anti-do-1 antibodies. Immunodiffusion has previously demonstrated the identical
specificity of the serum Su for serum Jo. As shown in
Figure lA, the Jo and Su sera demonstrated identical
immunoreactivities against CTE prepared in our laboratory (CTE-1) and CTE provided by Drs. Nishikai
and Reichlin (CTE-2). Figure 1B shows the immunologic distinction of the Jo-1 from the PM-1(serum We).
Figure 1C demonstrates that the Jo-1 system is distinct
from Mi-2 by the line formed between serum Mi and
CTNE 100 and Mi-1 (line formed between serum Mi
and CTNE 10). (In the latter, the Jo-1 system cannot
be visualized.) Thus, the difference of the Jo-1 system
YOSHIDA ET AL
606
Table 1. Frequency of precipitating antibodies to the Jo-l antigen in
connective tissue diseases
specific for PM-scleroderma overlap syndrome. One
of the interesting findings in this study is that every
PM-DM patient with antibodies to nRNP was classified in the overlap or MCTD groups, and none in the
uncomplicated PM-DM group.
Clinical findings in PM-DM patients with or
without antiJo-1 antibodies. The antibodies to the Jo-1
antigen were found to be highly specific for patients
with PM-DM or PM overlap syndrome. We then
looked for any differences between patients with antiJo-1 and those without. The sex ratio and mean age at
the time of diagnosis were not different between the
groups. Although the mean levels of serum myogenic
enzymes and serum immunoglobulins were higher in
the antibody positive group, the difference was not
significant. The initial dosage of steroids (38 mg
prednisolone/day for antiJo-1 positive and 46 mg
prednisolone/day for negative patients) was comparable between the groups. Their response to steroid
therapy (average period required for CPK levels to
return to normal was 41 days for anti-Jo-1 positive and
45 days for anti-Jo-1 negative patients) and mortality
(22% for anti-Jo-1 positive and 25% for anti-Jo-1
negative groups) were not different between the two
groups (Table 3). The characteristic skin eruption of
DM (Gottron’s sign: heliotrope discoloration a n d o r
skin rash over the extensor surface of the joints) was
observed in only 1 patient in the anti-Jo-1 positive
group (x2 = 4.62, P < 0.05).
Interstitial lung fibrosis demonstrated by chest
roentgenograms was found in every patient of the antiJo-1 positive group, while in the anti-Jo-1 negative
group it was found in only 5 (22%) patients. Although
this was statistically significant, there was no relationship between the titers of anti-Jo-1 antibodies and
severity of pulmonary fibrosis determined by chest
roentgenogram or diffusion capacity. One patient had
proteinuria and microscopic hematuria with decreased
creatinine clearance (26.8 mYminute). Both of the
patients with antiJo- 1 antibodies with overlap syndromes (PM-SLE and PM-scleroderma) had interstitial lung disease. Histologic findings of 1 patient are
~
Clinical diagnosis*
No. tested
No. positive
PM-DM
SLE
PSS
RA
MCTD
Overlap syndrome
PM-SLE
PM-PSS
PM-SLE-PSS
SLE-PSS
32
138
45
60
21
28
7
10
4
9
0
0
0
0
2
I
1
0
0
7
* PM = polymyositis; DM = dermatomyositis; SLE = systemic
lupus erythematosus; PSS = progressive systemic sclerosis; RA =
rheumatoid arthritis; MCTD = mixed connective tissue disease.
from the previously described systems was confirmed.
Frequency of the antiJo-1 antibodies. The incidence of the precipitating antibodies to the Jo-1 antigen is shown in Table 1. The antibodies to the Jo-1
were found only in patients who had myositis. Nine of
32 patients with uncomplicated PM-DM and 2 of 28
patients with overlap syndrome (1 with PM-SLE, 1
with PM-scleroderma) were positive for the anti-Jo-l .
None of the patients with other connective tissue
diseases or normal controls were positive for antibodies to the Jo-1 antigen.
Precipitating antibodies other than antiJo-1 in
PM-DM. The results of detailed analysis of precipitating antibodies other than anti-Jo-1 in 32 patients with
uncomplicated PM-DM and 21 patients with PM overlap syndrome (7 with PM-SLE, 10 with PM-scleroderma, 4 with PM-SLE-scleroderma) are shown in Table
2. In uncomplicated PM-DM, antibodies to SS-A were
found in 4 patients who were also positive to Jo-1; 6
patients showed unidentified precipitin lines. In the
PM overlap group, multiple antibodies were found
with various frequencies. In our PM-DM patient population, antibodies to the Mi-1 or Mi-2 were not
detected. Antibodies to the PM-1 were found in only 2
patients with overlap syndrome but in none of the
patients with uncomplicated PM-DM. As reported
elsewhere, antibodies to the Ku antigen were highly
Table 2. Frequency of the precipitating antibodies other than anti-Jo-1 in polymyositis-dermatomyositis(PM-DM)
Clinical diagnosis
No.
tested
SS-A
SS-B
RNP
Sm
PM-DM
PM-DM overlap
32
21
4
6
0
I
0
9
0
5
Antibodies to
Ku
Ki
Mi-1,2
0
7
0
6
0
0
PM-1
Scl-70
Others
0
2
0
0
6
4
AUTOANTIBODIES TO Jo-1 IN POLYMYOSITIS
607
Table 3. Clinical and laboratory findings in patients with or without anti-Jo-1 antibody
Anti-Jo-1 antibody
Positive
(n = 9)
Negative
(n = 23)
712
37. I
4,071 (44-5,984)
205 (36-673)
46 (8.2-63.9)
38
41
22
30
llt
17:6
43.4
1,138 (369,900)
137 (24-291)
17 (2.0-122)
46
45
26
39
70
22
1
3
I
0
415
48
0
0
26
Findings*
Fema1e:male
Age at diagnosis
CPK, IUAiter
SGOT,IU
Aldolase, IUAiter
Initial prednisolone/day, mg
Days to normalize CPK levels
Mortality, %
Mean followup, months
Skin rash, %
Pulmonary fibrosis, %$
I ground-glass pattern
I1 reticulonodular pattern
111 coarser pattern with cystic areas
IV honeycomb appearance
Decreased DLco, 5 15 muminute mmHg
Polyarthritis, %
Proteinuria, %
Hypocomplementemia, %
Rheumatoid factor, %
100s
1
5
3
0
516
loot
I1
44t
77t
~~
~
~
* CPK = creatine phosphokinase; SGOT = serum glutamic oxaloacetic transaminase.
t P < 0.05.
$
Radiologic grading.
5 P < 0.001.
described in the Case Report (patient 3). The joint
involvement was found in all patients with anti-Jo-1
antibodies and in 11 of 23 (46%) in the anti-Jo-1
negative group. A characteristic of the joint disease
was a nonerosive polyarthritis with a distribution
pattern similar to rheumatoid arthritis.
Anti-Jo-1 antibodies and disease activity. The
relationship of the anti-Jo-I titer and activity of myositis was studied. In each patient, the antiJo-1 titer
decreased when the muscular inflammation became
quiescent, in 1 patient becoming undetectable (Figure
2). The anti-Jo-1 titer and disease activity, however,
were not always parallel.
CASE REPORTS
Patient 1 (Figure 3). A 52-year-old housewife
was first admitted in 1972 to the Keio University
Hospital because of malaise, easy fatigability, and
weakness. On admission, she was found to have
weakness in the neck flexor muscles and the proximal
muscles of all extremities and pain on motion in both
shoulders. Laboratory examination disclosed elevated
serum CPK (960 IU/liter) and aldolase (28 IU/liter).
The electromyogram showed spontaneous fibrillation
and short duration potentials. A biopsy specimen of
her right gluteal muscle disclosed degeneration and
necrosis of muscle fibers with infiltrates of chronic
inflammatory cells. Prednisolone therapy, 30 mg daily,
resulted in a marked improvement of her clinical and
laboratory abnormalities. In late 1972, she developed
dry rales bilaterally at the kung bases. The chest
roentgenogram and diffusion capacity for carbon dioxide (DLco) were normal.
During the following years, steroid doses were
adjusted according to serum CPK levels. From early
1978, she began to notice shortness of breath and
palpitation with physical activities. The DLco showed
a gradual decrease and the chest roentgenogram disclosed the presence of bilateral interstitial fibrosis.
Retrospective study of stored sera showed positive
anti-Jo-1 precipitins from the earliest specimen. The
anti-Jo-1 titers, which had declined after initial steroid
therapy, showed a concomitant rise when the serum
CPK level increased in 1978.
This patient presented typical features of polymyositis including proximal muscle weakness, elevated myogenic enzymes, electromyogram, and histology. Retrospective study of her sera showed presence
of anti-Jo-1 antibodies prior to the appearance of
interstitial lung disease. The titers of anti-Jo-1antibodies correlated with activity of muscle disease.
Patient 2 (Figure 4). A 37-year-old woman first
YOSHIDA ET AL
608
. I912
1
128
R
-
.
. 1114
.
.
1916
.
.
1111
,
llM
,
r'
L
.-5 1 : 6 4
I-
30
1.92
C
1:16
4
1 : 8
A
??
c.
-a
Figure 3. Clinical course of patient I , a 52-year-old woman, demonstrates the presence of anti-Jo-l antibodies before the appearance of
pulmonary fibrosis. The rise of anti-Jo-1 titer was associated with
active myositis as shown by increased myogenic enzymes.
1: 4
1: 2
Undil.
Net3
+
PM a c t i v i t y
Figure 2. The anti-Jo-l titer and activity of muscle inflammation.
Antibody titers to the Jo- I were compared in an individual patient in
both active and inactive stages. The anti-Jo-l titers decreased when
the myositis became inactive after steroid therapy.
noted polyarthralgia in her proximal interphalangeal,
metacarpophalangeal, and knee joints in 1972. The
symptoms responded to nonsteroidal antiinflammatory drugs prescribed by her doctor. In 1975, she
noticed fatigability, polyarthritis, weakness, and dysphagia and was admitted to the Keio University Hospital. On examination, she was found to have moderate weakness in her neck flexor muscles, limb girdles,
and proximal muscles bilaterally. There were no skin
rashes or active synovitis. Blood chemistry disclosed
elevated myogenic enzymes (CPK 2,100 IU/liter, aldolase 420 Wliter). Electrornyogram showed low
voltage and polyphasic discharges. The biopsy specimen from the right quadriceps muscle disclosed necrosis of muscle fibers with focal aggregations of chronic
inflammatory cells. Prednisolone therapy at a daily
dose of 30 mg was initiated, to which the patient
showed good response.
In 1979, she began to notice shortness of
breath, and superficial cracking rales were heard at
both lung bases. The chest roentgenogram which
previously was normal showed interstitial fibrosis, and
the DLco was decreased to 11.5. Her serum samples
showed antibodies to the Jo-1 antigen throughout her
followup period. The titers of anti-Jo-1 decreased
gradually after steroid treatment. When her serum
CPK level increased in 1980, a rise of anti-Jo-l titer
was also observed.
During observation, this patient twice developed elevated CPK, and each time she had high antiJo-I titers. As in patient 1, this woman developed
interstitial pulmonary fibrosis during followup, and an
association of the anti-Jo-1 titer with activity of her
myositis was evident.
Patient 3 (Figure 5). This woman had been in
good health until age 56 when she developed bilateral
shoulder pain and myalgia in her arms and legs. At the
age of 59, she first noticed Raynaud's phenomenon
and was admitted to Keio University Hospital. On
admission, fine dry rales at both lung bases and slight
tenderness of the proximal muscles of her arms and
legs were present. Serum CPK was elevated to 262
IU/liter. and titer of Jo-l antibody was 1:128 by
immunodiffusion. Fluorescent antinuclear antibody
was positive with a titer of 1:64 and homogenous
lixk-unu
c.-8..d..m
A
-
A
-
+
+
Figure 4. Patient 2, a 37-year-old woman. This graph shows that
increased titer of anti-Jo-l was associated with active muscle
disease. The interstitial lung fibrosis became evident during the
followup period.
AUTOANTIBODIES TO JO-1 IN POLYMYOSITIS
1971
1974
. 1916
1918
l9M
609
DISCUSSION
P-3-
10114
G ~ l nr&s
l
+
+
Figure 5. Patient 3. This illustration demonstrates clinical course of
this 65-year-old woman with polymyositisSLE overlap. Association between the rise of anti-Jo-l titer and increased clinical activity
was observed.
pattern. Antibodies to DNA were found by counterimmunoelectrophoresis. Two weeks after admission,
CPK was elevated further to 732 Whiter, add the
diagnosis of polymyositis was made based on the
myogenic pattern of electromyogram, degeneration of
muscle fibers, and inflammatory cell infiltrates found
in the deltoid muscle biopsy specimen. Her muscle
symptoms responded to the increased dose of corticosteroid (20 mg/day of prednisolone), and she was
discharged on the 300th hospital day.
Sixteen months later she was readmitted because of profuse proteinuria (5.4 gdday) and orthopnea. No signs of active myositis were found. After
readmission her renal function deteriorated, and 2
months later she died of congestive heart failure at age
65.
At autopsy, histologic examination revealed
atrophy and lipid infiltration with diffuse or focal
inflammatory infiltrate of mononuclear cells in striated
muscles of various locations. In the lung, severe
alveolar fibrosis had resulted in obliteration of alveolar
spaces; a few epithelialized alveolar remnants and
bronchiolectasia were observed in the fibrotic tissue
(Figure 6). There was a moderate interstitial chronic
inflammatory cell infiltration. The kidney showed diffuse mesangial proliferation with focal segmental sclerosis and hyalinosis.
This patient presented characteristic features of
polymyositis including proximal muscle weakness,
elevated serum enzymes, myogenic pattern on electromyogram, and typical histologic findings in biopsy and
autopsy specimens. The clinical evidence of her interstitial lung disease was confirmed at autopsy. The
presence of Raynaud's phenomenon, polyarthritis,
and renal disease (profuse proteinuria and cylinduria)
classified this patient in the PM-SLE overlap syndrome group. Detailed histologic findings were reported elsewhere (21).
The Ouchterlony double immunodiffusion technique has proved a useful tool for the analysis of
precipitating antibodies in the connective tissue diseases (22). Even though soluble extracts of isolated
nuclei or whole tissue are heterogeneous antigen
sources, immunodiffusion offers the necessary resolving power to identify specific antigen-antibody reactions. The specificity of precipitins in a test serum can
be determined by monospecific standard sera of
known specificities. Studies in which this technique is
used have revealed a number of antibody systems with
substantial clinical importance (1-3).
Among the connective tissue diseases, autoimmune phenomena in PM-DM have been reportedly
less frequent than in other diseases such as SLE or
scleroderma (5,23,24). Antinuclear antibodies detected by immunofluorescence have been reported in 530% of patients with PM-DM (5.23.24). However,
little attention has been paid to disease specific reactions until 1976 when Reichlin and Mattioli reported
that 59% of PM patients (10 of 17) and 2% of controls
(3 of 84) had autoantibodies reactive with a nuclear
antigen, termed Mi, by a modified complement fixation test (4).
It is important to note that antibodies reactive
with certain nuclear antigens such as Jo-l or Ku
cannot be detected by standard immunofluorescence
technique on tissue sections of rodent organs (8,101.
Indeed, 2 of 11 anti-Jo-1 positive patients had negative
FANA tests in the present study.
Figure 6. Histopathologic findings of the lung obtained from patient
3 at autopsy demonstrated chronic interstitial disease. (Hematoxylin
and eosin. original magnification x400.)
610
In a subsequent study, Nishikai and Reichlin
found that the Mi system contained two precipitating
antibody systems, termed the Mi-1 and Mi-2 (25).
These investigators reported a lower incidence of antiMi antibodies using immunodiffusion technique with
partially purified Mi antigens (2 anti-Mi-1 and 1 antiMi-2 of 46 PM-DM patients) (25). Subsequently,
Wolfe et al described a precipitating antibody named
PM-1 in 61% (I7 of 28) PM patients ( 5 ) . Antibodies to
the PM-1 were observed more frequently in PM (9 of
14,64%) and PM-scleroderma overlap syndrome (7 of
8, 87%) than in DM (1 of 6, 17%). More recently,
Nishikai and Reichlin reported the considerable heterogeneity of precipitating antibody systems in PMDM patients (7,8). They described 9 calf thymus
antigens reactive with PM sera; the Jo-1 antibody
system were reported most frequently, occurring in 8
of 26 PM and 1 of 22 DM patients. From our laboratory, two precipitating antinuclear antibody systems,
the Ku and Su, that are associated with PM patients
have been reported (9). The patients with antibodies to
the Ku antigen are characterized by an overlap syndrome of PM and scleroderma (10).
In the present study, immunologic identity of
the Su and Jo-1 systems and their difference from the
PM-1 system were confirmed. Antibodies to the Jo-1
antigen were highly specific for PM. Among the I f
patients who were positive for anti-Jo-I, 9 had PM and
2 had overlap syndromes of P M S L E and PM-scleroderma. Only 1 patient with typical skin rashes was
classified as having DM. In our patient group, antibodies to the Mi-1 or Mi-2 were not observed. Antibodies
to the PM-1 were found in 2 patients with PMscleroderma but not in patients with uncomplicated
PM or DM. Further work should clarify the reasons
for the different results obtained in the present study
from those of previous works.
In a given patient, titers of anti-Jo-1 antibodies
correlated with the activity of myositis. In contrast to
antibodies to DNA, the titers of which reflect disease
activity in SLE, the absolute titer of anti-Jo-1 cannot
be used as a marker of disease activity (26). In 6
patients whose sera were selected at both active and
inactive stages by a precise criteria for myositic activity, anti-Jo-1 titers decreased when the muscle inflammation subsided after steroid therapy. However, in the
3 patients whose case reports were included in this
paper, relationship between anti-Jo-1 titer and disease
activity were not always parallel. Therefore, further
studies should be conducted to clarify this point.
Patients with PM-DM who had anti-Jo-1 anti-
YOSHIDA ET AL
bodies have higher incidence of extramuscular symptoms (such as interstitial pulmonary fibrosis and polyarthritis) and immunologic abnormalities (such as
hypergammaglobulinemia and rheumatoid factor) than
those who did not have anti-Jo-1 antibodies. The lung
involvement observed in the present study showed
typical clinical and roentgenographic findings of interstitial pulmonary fibrosis with gradual onset. Three
patients with anti-Jo-1 antibodies developed lung disease during the followup periods. This demonstrates
not only the predictive value of antiJo-1 antibodies
but also the importance of the time at which test serum
is obtained to determine anti-Jo-1 titers.
The results of this report are in contrast to the
study by Arnett et al who reported that anti-Jo-I
antibodies, although specific for PM, were not associated with particular clinical characteristics (27). Although the recent report of Brundin (28) indicated that
pulmonary fibrosis might be more frequent than previously thought, it has rarely been reported in the
English literature (29,30). In our series, interstitial lung
fibrosis was observed in 14 of 32 patients (44%: 9 of 9
anti-Jo-1 positive and 5 of 23 anti-Jo-1 negative patients). Possibly the racial or ethnic backgrounds
might account for the clinical differences between our
patients and those of Arnett.
Serologic studies of patients with connective
tissue diseases disclose a variety of autoantibodies
reactive with non-organ specific antigens. Close associations are demonstrable between the specificities of
these autoantibodies and clinical expressions of autoimmune diseases. Althobgh the mechanisms of these
associations are not known, the presence of specific
antibodies before the appearance of associated clinical
manifestations suggests that these serologic abnormalities are not the simple result of tissue damage. Recent
studies indicate that genetic factors might be involved
in the production of specific autoantibodies. Sasazuki
et a1 reported that in Japanese patients antibodies to
nRNP and DNA are associated in HLA-Dwl and
HLA-Blw35, respectively (31). In two studies, associations have been described between antibodies to Ro,
Jo-1, and HLA-Dw3 (27,32). Further studies to explore the mechanisms of these associations and the
significdnce of these serologic reactions should improve upderstanding of the underlying pathogenesis of
conneche tissue diseases.
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AUTOANTIBODIES TO Jo-1 IN POLYMYOSITIS
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