Anti-Ku autoantibodies are frequently associated with scleroderma (PSS)-polymyositis (PM) overlap syndrome in Japanese patients. However, it has been also reported that anti-Ku antibodies are detected mostly in SLE patients in USA by enzyme-linked immunosorbent assay (ELISA) using a monoclonal anti-Ku antibody. To establish more sensitive detection system of anti-Ku antibodies, recombinant fusion proteins between Ku antigens and β-galactosidase expressed from isolated cDNA clones encoding the Ku proteins were purified and used them as antigens for ELISA.
The 70kDa-Ku fusion protein (70kDa-Ku coupled with β-galactosidase: fp 70) and the 80kDa-Ku fusion protein (80kDa-Ku coupled with β-galactosidase: fp 80) were successfully purified through electro-elution from polyacrylamide gel slices without loss of immunoreactivity. New ELISA systems using these two fusion proteins were established and tested to detect the reactivity of sera from 126 patients with various systemic rheumatic diseases and normal healthy controls. Anti-Ku antibodies were detected in 77% and 46% of patients with overlap syndromes by fp 70-ELISA and fp 80-ELISA, respectively. Moreover, the sera from patients with PSS-PM overlap were revealed to contain the highest titers in both ELISA systems. Anti-Ku antibodies detected by both ELISAs were less frequent and with lower titers in patients with SLE, PSS, PM/DM and MCTD. ELISA using β-galactosidase as a control was weakly positive only in 5% of 126 patients and 20 normal healthy persons. These results indicate that ELISA using purified recombinant fusion proteins may be a good assay system for detecting anti-Ku autoantibodies.

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Effects of immunoglobulin (IG) therapy on complement system was studied on 11 patients with serious lung infection. Complement hemolytic activities (CH 50 and ACH 50), complement profile and complement fragments (ic 3 b, Bb and C 4 d) were investigated in peripheral blood time proceedingly.
ACH 50, factor B, C 3 and C 9 decreased by IG therapy. Bb increased early, and iC 3 b increased lately. CH 50 and C 4 d showed no differences. Those results clarified IG therapy accelerated the activity of alternative complement pathway in patients with serious lung infection. An experiment in vitro comfirmed IG had direct activation to factor B. Those facts suggested that biological significance of IG therapy were present in both efficacious bacteriolysis with complement and adequate modification to complement system. This study also present the necessity to identify biological function of Bb and iC 3 b.

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We described two cases of refractory IgG myeloma (67 year-old female and 72 year-old male) who developed autoimmune hemolytic anemia with positive Coombs' antibody during the course of alpha-interferon therapy.
Those findings suggest that the development of autoantibodies in these myeloma patients was resulted from interferon administration, since most of the patients with myeloma have moderately decreased serum levels of polyclonal Igs and show impaired antibody formation after antigenic stimulation. There has been no report of such cases in the literatures.

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We investigated optimal conditions for induction of cytotoxic T lymphocytes (CTL) by in vitro sensitization (IVS). Each peripheral mononuclear cells from 8 patients with gynecologic malignancies were incubated with MMC-treated cancer cells for 18 days with rIL 2. The degree of both antitumor activity and proliferation of CTL was affected by the IL-2 concentration and the ratio of number of MMC-treated cancer cells to that of lymphocytes used for culture. Incubation with 800 JRU/ml of rIL 2 produced maximal CTL induction. And at the ratio of 1:10, maximal CTL induction was attained. Thus CTL was optimally induced by mixed cultivation of the lymphocytes and cancer cells at the 10:1 with rIL 2 added at the concentration of 800 JRU/ml. The 4 patients with gynecologic malignancies were treated with CTL and rIL 2. The CTL therapy was effective for peritnitis carcinomatosa in these patients, but no objective regressions of cancer were observed.

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Sjögren's syndrome (SS) is occasionally reported in patients with hepatobiliary diseases such as chronic hepatitis and primary biliary cirrhosis. However, the incidence and type of hepatobiliary diseases in patients with SS has not fully been evaluated. We surveyed hepatobiliary diseases in 162 patients with SS and found that 15 patients with SS disclosed hepatic dysfunction without any hepatitis B virus markers or history of excessive alcohol intake and blood transfusion. The pathological study of liver biopsies from 14 patients revealed 4 with chronic persistent hepatitis, 5 with chronic active hepatitis and 5 with primary biliary cirrhosis. Abnormal salivary gland lesions were found in 11 of 13 patients with SS and hepatic dysfunction, whereas they were found in 50 of 103 patients with SS without hepatic injury (p<0.025). Anti-hepatitis C virus associated antibody (HCV-Ab) was positive in 5 of 6 patients with chronic persistent hepatitis or active hepatitis, and negative in all 3 patients with primary biliary cirrhosis examined. The optical density values of HCV-Ab in 4 of the 5 HCV-Ab positive patients were more than 3.0. These findings suggest that the greater part of chronic hepatitis associated with SS might be caused by infection of hepatitis C virus in Japan, and that primary biliary cirrhosis might be the most likely complication of SS.

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A case of pancytopenia induced by low dose methotrexate (MTX) therapy for rheumatoid arthritis was reported. Thirty-nine years old woman admitted to our hospital because of reiterate fever and polyarthralgia. She had taken prednisolone (PSL) because of fever, morning stiffness and polyarthralgia, with a possible diagnosis of adult onset Still's disease, for 7 years. On admission she was diagnosed as rheumatoid arthritis, because of morning stiffness and proliferating synovitis, with complication of secondary amyloidosis, renal dysfunction and hypoalbuminemia. Low dose MTX therapy (5mg/week) was begun with a partial response. However, stomatitis and pancytopenia occurred 6 weeks later, and rapidly progressed. MTX was discontinued, and she was successfully treated by leucovorin and G-CSF.
Low dose MTX therapy has been reported to be effective for rheumatoid arthritis and severe side effect is rare. She was positive for drug-lymphocyte stimulation test to MTX (SI=441%) and it was speculated that lymphocyte-mediated cytotoxicity in addition to its direct toxicity might be responsible for pancytopenia in this case.

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In November 1986, a 37-year-old female patient was diagnosed as systemic lupus erythematosus (SLE) because of photosensitivity, butterfly rash, positive antinuclear antibody and positive anti DNA antibody, and thereafter she had been treated with prednisolone in the department of dermatology of our college.
In Decemmber 1989, she was transferred to our department because of general fatigue and paresis in her both legs. The titers of antinuclear antibody were 1 to 2, 560 and anticardiolipin (aCL) antibody were a titer of 73U/ml. Her head CT scan showed multiple cerebral infarction and she was treated with prednisolone at initial dosage of 40mg per day with a slight improvement of clinical symptoms. However, she stopped taking prednisolone by her own will. In May 1990, she was re-admitted because of complete paralysis and sensory disturbance on her both feet and vesico-urethral disturbance with a high titer of aCL antibody (94U/ml). She was diagnosed as transverse myelopathy associated with SLE with positive aCL antibody.
Treatments of pulse therapy with methylprednisolone, oral administration of cyclophosphamide, intravenous administration of γ-globulin as large as 15g per day for 5 days, and plasma exchange were not effective on neurological symptoms, in spite of decreased titer of aCL.
Early treatment seemed to be necessary for clinical improvement of transverse myelopathy.

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A rare case of systemic lupus erythematosus (SLE) with pituitary adenoma was reported. A 32-year-old woman who had been diagnosed as SLE in 1987 was readmitted to our hospital because of abnormalities of both sight and visual field in April 1990. Brain CT revealed homogeneous tumor that showed clear border within pituitary gland. MRI examination also displayed similar findings except that a part of the tumor invaded into sphenoid sinus. TSH, T₃, T₄ and prolactin were slightly elevated in endocrinological examinations. After total removal of pituitary adenoma by transsphenoidal approach in 19 April, the abnormalities of both sight and visual field was remarkably improved, and antinuclear antibodies changed into negative. It was suspected endocrinological abnormalities except for sex hormone might be also concerned in immunological disorder of SLE.

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A 51-year-old male with rheumatoid arthritis (stage III, class II) was admitted to our hospital because of progressive proximal muscular weakness with atrophy. Laboratory data showed elevated levels of myogenic enzymes including creatine kinase. Electromyogram showed myogenic changes and deltoid muscle biopsy demonstrated muscle atrophy with marked inflammatory cell infiltration showing follicle formation. Further examination revealed a complication of Sjögren's syndrome associated with monoclonal gammopathy. He started to be treated with 40mg/day of prednisolone (PSL) with remarkable clinical responses. Insidious but progressive muscular weakness with atrophy became evident, however, when PSL was tapered to 10mg/day. Concomitant use of oral cyclophosphamide was not effective and he was again admitted. Both proximal and distal muscular atrophy was prominent with mild elevation of myogenic enzymes. Light microscopy of muscle biopsy specimens showed degenerative muscle fibers with numerous rimmed vacuoles. Furthermore, electron microscopy disclosed intranuclear and intracytoplasmic inclusions, and a definite diagnosis of inclusion body myositis (IBM) was made. Whether he had IBM from the beginning or had polymyoistis in his early course as an initiation of IBM is discussed on the basis of immunohistochemical studies.

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Familial cases of HLA-B 27 associated spondyloarthlopathy were reported.
A 54-year-old male visited our hospital with the symptoms of ankle and wrist joints pain. He had been suffering from lumbago for 34 years, and uveitis for 7 years. The titer of antibody for Chlamydia trachomatis was slightly elevated. The X-ray examination revealed the bilateral sacroiliitis, squaring of the lumbar spine, syndesmophyte formation of the spine and enthesopathy. He was diagnosed as having ankylosing spondylitis (AS).
The son of this patient, 25-year-old male, was consulted to our hospital with the complaints of knee joint pain and lumbago. He had been suffering from non-gonococcal urethritis for three months before the onset of the articular symptoms. Laboratory findings revealed the elevation of ESR and CRP, and negative rheumatoid factor. Unilateral sacro-iliitis was found on X-ray film. He was diagnosed as having Reiter's syndrome.
Both cases were HLA-B 27 positive. This is the first report on the familial cases of AS and Reiter's syndrome in Japan.

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We report a case of a 18-year-old woman with aortitis syndrome complicated by erythema nodosum. When she was 6 years old, she was admitted to the hospital because of a 2-month history of intermittent high fever. The diagnosis of aortitis syndrome was suggested by the absence of the both upper limb pulses and confirmed by angiography. Stenosis and/or occulusion were observed in aorta and its major branches. She got better aftter the administration of corticosteroid. Thereafter three times of flare-up of aortitis syndrome were controlled by corticosteroid therapy. Clinically she had been well with the low dosage of prednisolone for about these two years. She visited our hospital when she was 18 years old. On physical examination, there was no active vascular symptom and no bruit. However, her laboratory data showed mild inflammatory reactions; erythrocyte sedimentation rate (ESR) was 32mm/h, and C-reactive protein (CRP) was 3.4mg/dl. Two weeks after the tapering of the daily dosage of prednisolone from 10mg to 9mg, erythema nodosum was noted on her knees and feet. Her laboratory data (ESR and CRP) worsened to some extent. The biopsy specimen from her right foot obtained on the 7th day revealed marked granulomatous vasculitis associated with aggregation of neutrophils, eosinophils, lymphocytes, and multinucleated giant cells around the small arteries, capillaries, and veins. Furthermore granulomatous panniculitis was also observed. The administration of prednisolone 20mg per a day led inflammatory reaction and cutaneous lesions to the rapid resolution. Two months later the bruit was ausculated on her right neck temporarily.
In Japan, erythema nodosum has rarely been reported with aortitis syndrome. Moreover, it was suggested that granulomatous inflammation in the small size arteries could occur in aortitis syndrome.

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