Urinary autoantibodies, focussing on immunoglobulin G (IgG), and various autoantibody activities, were investigated. There were significant correlation between urinary ANA titers and urinary IgG levels (p<0.001), and between urinary and serum ANA titers (p<0.001). Patients with speckled staining pattern of serum ANA showed higher frequencies in the appearance of urinary ANA (p<0.01).
Using ELISA, patients with anti-DNA antibody and Anti-Sm antibody were investigated. We could find a significant difference between the ratio of urinary anti-DNA and that of anti-Sm antibodies (p<0.01).
Urinary ANA may be unsuitable as a indicator of routine diagnosis for early renal involvement, but seems to reflect indirectly to the potentiality of renal trapping of antibodies.

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In order to investigate abnormalities of cytokine production in Graves' disease, we measured ability of mononuclear cells (PMC) obtained from patients with Graves' disease and healthy subjects to produce interleukin-1 (IL-1) and interleukin-2 (IL-2) activities. The effects of anti-thyroid drugs on the production of IL-1 and IL-2 in PMC of healthy subjects were also examined. Both IL-1 and IL-2 activities in culture supernatants were determined by radioimmunoassay. When monocytes purified from PMC were stimulated with lipopolysaccharide (LPS), IL-1 release in culture supernatants was significantly higher in Graves' disease patients with hyperthyroid function compared with in healthy subjects and the patients with euthyroid function. IL-2 production in phytohemagglutinin (PHA)-stimulated PMC culture was significantly lower in Graves' disease patients with hyperthyroid function than in healthy individuals. Methimazole (MMI) and propilthiouracil (PTU) suppressed the LPS-induced IL-1 production in monocytes from healthy subjects in a dosedependent manner. MMI enhanced PHA-induced IL-2 production in PMC from healthy subjects, whereas PTU had no effects. Triiodothyronine (T₃) enhanced IL-1 production in two of four normal subjects in repeated experiments, suggesting that there exists heterogeneity of the effects of T₃ among individuals. Thus, it is expected that these abnormal findings of increased IL-1 and decreased IL-2 production observed in Graves' disease patients with hyperthyroid function will be futher modified by thyroid hormone and administration of anti-thyroid drugs.

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Antiphospholipid antibodies, antibodies to cardiolipin (CL) and to phosphatidyl serine (PS), were measured in the sera of 197 patients with various collagen diseases, including 108 patients with systemic lupus erythematosus (SLE), 29 patients with mixed connective tissue disease (MCTD), 39 patients with rheumatoid arthritis, 13 patients with Sjögren's syndrome and 8 patients with scleroderma. IgG anti-CL antibodies were found in 68 (63%) of SLE, 18 (62.1%) of MCTD, 13 (33.3%) of rheumatoid arthritis, 9 (69.2%) of Sjögren's syndrome, and 2 (25%) of scleroderma. IgG anti-PS antibodies were also found in 39 (36.1%), 15 (51.7%), 10 (25.6%), 9 (69.2%), and 1 (12.5%), respectively.
In patients with SLE both antibodies were significantly related to thrombocytopenia, CNS lupus and spontaneous abortion. In patiens with MCTD there was a significant association between antiphospholipid antibodies and pulmonary hypertension. In patients with rheumatoid arthritis anti-CL antibody was significantly associated with positive antinuclear antibody, positive anti-SSA antibody and sicca symptom.

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Immunoassays for human immunodeficiency virus (HIV) antigens and for antibodies to HIV core and envelope were done on serial sera from 6 patients (3 hemophiliacs and 3 sexual transmitted patients), who had become seropositive on screening by particle agglutination test.
Antibodies to HIV envelope by ENVACOR EIA assay were detected in all patients and antibodies to HIV core in 4 of 6 patients. By western blot assay, both gp 41 and gp 120 bands were found in all patients, and the p 24 band were detected in 5 of 6 patients. The results of ENVACOR EIA assay were not exactly compatible with those of western blot assay.
The p 24 HIV Ag was positive in only one patient and was negative in 5 patients. But one of 5 negative sera was found to be positive after the treatment of these sera with acid and heat.
These results suggest that detection of HIV-Ag after treatment of sera by acid and heat to dissociate antige from immune complex was useful for the disease monitering.

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Paired serum and cerebrospinal fluid (CSF) specimens from 83 patients with various neurological diseases were studied for CSF-serum α₂-macroglobulin (α₂M) quotient (Q_α2M), using a sensitive enzymeimmunoassay. The concentrations of CSF α₂M in 18 control patients were 2.55±0.92μg/ml (Mean±SD), and were significantly correlated with those of serum α₂M (r=0.65). Q_α2M was significantly correlated with CSF-serum albumin quotient (Q albumin) in 61 patients with noninflammatory neurological diseases (control, spinal spondylosis, cerebrovascular disease, degenerative diseases) as well as in 22 patients with inflammatory neurological diseases (multiple sclerosis, infectious meningoencephalitis) (r=0.73 and r=0.91, respectively). The ratio of Q_α2M/Q albumin in control patients was 0.26±0.08 (Mean±SD). There was no significant difference in the ratio of Q_α2M/Q albumin among various neurological diseases. However, the ratio of Q_α2M/Q albumin was significantly decreased in 4 patients with infectious meningoencephalitis when they recovered from the manifestations after treatment. These results indicate that Q_α2M is one of the successful tools for the evaluation of the blood-brain barrier function. Moreover, the data suggest that Q_α2M might reflect the damage of blood-brain barrier in a more sensitive fashion than Q albumin.

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Common variable hypogammaglobulinemia (CVH) includes a variety of disorders. The pathogenetic mechanisms responsible for the impaired immunoglobulin production in CVH are diverse with abnormalities in both B cells and immunoregulatory T cells. In this report, 11 cases with CVH were analyzed regarding the function of immunoglobulin production by means of enzyme immunoassay (EIA). In all cases, very low dose immunoglobulins were detected in culture supernatant. The enhancement of Igs production was not revealed in pokeweed mitogen induced culture system. In 6 of 11 cases B cell functions were disturbed. The others (5) were demonstrated T cell dysfunction. Moreover, 3 cases of them were proved the hyperfunction of the suppressor activity.
Recent report shows that cimetidine, an antagonist to histamine H₂-receptors decreases excessive suppressor activity and allows endogeneous immunoglobulin production in some patients with CVH. So, the effect of cimetidine on immunoglobulin production was examined with two patients demonstrated hyperfunction of the suppressor activity. Two cases were given a one-month course of oral cimetidine. Serum immunoglobulin concentrations rose slithtly in one case and held the same level in another case. These effects were reversible after the drug was stopped. There was no difference in cell surface marker analysis, in vitro immunoglobulin production and suppressor activity while taking cimetidine.
These results suggest that cimetidine may allow endogeneous immunoglobulin production in some patients with CVH. But this mechanism of cimetidine efficasy is not clarified. Further investigation should be observed.

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Recent knowledge accumulated in the field of basic research about the differentiation and development of IgE-producing cells suggests a possibility that corticosteroids may inhibit the production of IgE in atopic patients. However, there have been very few clear-cut clinical studies concerning the suppressive effect of corticosteroids on the serum IgE level of atopic patients. Recently, we experienced a patient of systemic lupus erythematosus (SLE) with atopic dermatitis and marked serum hyperimmunoglobulinemia-E, who received corticosteroid-pulse therapy. We studied the time course of the changes in the levels of his serum IgE and IgE antibodies after the initiation of an ultra-high dose glucocorticosteroid therapy. The results obtained indicated that high-dose corticosteroid therapy suppresses the production of serum total IgE as well as specific IgE antibodies directed to house-dust mites and Japanese-cedar pollen. This inhibitory effect of corticosteroids on the production of IgE antibodies varied depending on the specificity of the IgE antibodies. At the same time, it was shown that high-dose steroid therapy suppresses the formation of anti-mite IgG antibodies. We believe that this is the first report showing the conclusive results concerning the suppresive effect of glucocorticosteroid therapy upon the formation of IgE and IgG immunoglobulins and specific antibodies.

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A 25-year-old male patient, with epilepsy, was admitted to our hospital because of a high fever, erythema, arthralgia and myalgia. He had been taking anticonvulsive drugs, such as diphenylhydantoin, since he had first begun having convulsive seizures twenty years ago. At the time, he had experienced convulsive seizures several times a year. Since drug-induced lupus was suspected, diphenylhydantoin was discontinued immediately. Clinical symptoms, however, did not improve three weeks after the discontinuation of diphenylhydantoin. The laboratory examination showed a low level of serum complement and a positive reaction of both anti-double stranded DNA antibody and anti-Sm antibody. These were regarded as incompatible findings for drug-induced lupus. In addition, since his mother also suffered from SLE with PSS, we suspected he had lupus diathesis. Interestingly, an immunological examination revealed a low level of serum IgA. Thus, he was finally diagnosed as a native SLE with selective IgA deficiency. After a combination of prednisolone and azathioprine was administered, the symptoms gradually improved. However, serum IgA did not return to within the normal range during hospitalization. The relationships between SLE, IgA deficiency, and the long-term administration of anticonvulsive drugs discussed.

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A case of tubulo-interstitial nephritis and anterior uveitis after silicone augumentation mammoplasty was reported. The patient was 21-year-old woman and she has had left ocular pain and high grade fever which started one month ago and was diagnosed as bilateral anterior uveitis ophthalmologically. Blood tests revealed presence of inflammation with prominent elevation of serum CRP value and ESR and she was administered antibiotics and anti-inflammatory drugs for ten days before admission. She received silicone augmentation mammoplasty seven months before admission.
At admission, physical examinations revealed no particular findings except continuous low grade fever of 37°C. The results of blood tests were as follows; hematocrit 31.6%, WBC 7, 100, CRP 3.5mg/dl, ESR 100mm/hr and serum IgG 2, 085mg/dl. Chest CT showed a high density area between major and minor pectoral muscles consistent with the area of previous silicone implantation, although chest X-P showed no obvious findings. ⁶⁷Gallium scintigraphy showed high accumulations at the site of silicone implantation, eyes and kidneys bilaterally.
We have suspected the silicone implantation as one of the major causes of the abnormal findings, and removed silicone surgically. One week after the removal, clinical and laboratory findings improved immediately. Furthermore, follow-up ⁶⁷Gallium scintigraphy revealed prominent improvement. Renal biopsy was also performed and revealed presence of tubulo-interstitial nephritis.
This is an extremely rare case which we found no previous report, and supposed that, with immunological reaction, silicone augmentation mammoplasty may cause tubulo-interstitial nephritis and uveitis.

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A case of hereditary angioneurotic edema (HANE) associated with Sjögren's syndrome is described. A 15-year-old female had been suffering from recurrent and sudden attacks of colicky abdominal pain since 11 years of age. Complement studies revealed low CH 50, C4 and C1 inhibitor levels, with normal C1q and C3 levels. No complement system defects were documented in other family members. However, normal C1 level, absence of lymphoproliferative diseases by gallium scintigram and undetectability of antibodies to C1 inhibitor suggest the patient suffered from HANE due to a spontaneous mutation of the C1-INH gene. She was also diagnosed as having Sjögren's syndrome from parotid sialogram findings and histological examination of minor salivary glands of the lip. Although several investigators have reported the cases of HANE associated with systemic lupus erythematosus, HANE associated with Sjögren's syndrome has not been fully documented.

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A 28 year old woman was admitted to our hospital because of exertional dyspnea. She was diagnosed by cardiac catheterization as primary pulmonary hypertension (PPH). Some laboratory findings such as positive anti-nuclear antibody, leucopenia and hypergam-maglobulinemia suggested that she had connective tissue disease (CTD), but any diagnostic criteria for CTD were not fulfilled. On month after the diagnosis of PPH, she developed butterfly rash and high titer of anti-dsDNA antibody and fulfilled the criteria for systemic lupus erythematosus (SLE).
Corticosteroid therapy and plasma exchange decreased the pulmonary artery pressure as well as the disease activity. She was a rare case who developed pulmonary hypertension prior to the diagnosis of SLE. PPH may be successfully treated by these therapy if immunological disorders are involved in its pathogenesis.

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Soft tissue calcification is sometimes found in scleroderma and dermatomyositis, however, to our knowledge, only 29 cases of systemic lupus erythematosus (SLE) were reported to have soft tissue calcification. And calcification in other tissues in addition to skin and subcutaneous tissue were documented in 3 cases. We report a 57 year old woman with arterial and basal ganglia calcification in addition to wide spread and large amounts of calcium depositions in subcutaneous tissue. In 1971, this patient was diagnosed as SLE, having butterfly rash, pancytopenia, arthralgia, elevated erythrocyte sedimentation rate, hypergammaglobulinemia, and positive ANF. Thereafter, she was treated with steroid. In 1985, she noticed small subcutaneous nodules on her hip. These nodules became larger and new nodules appeared, and histological examination revealed calcium deposition. In 1990, she was hospitalized because of effort dyspnea. The roentgenogram and the CT scan showed nodular calcification not only in the subcutaneous tissues of hip, upper and lower extremities, and thoracic wall, but also in aortic arch, thoracic and abdominal aorta, common iliac artery, internal cevical artery, and basal ganglia. The CT scan of pelvis revealed that the calcified lesion was restricted to superficial subcutaneous tissues, and did not invade muscle. The infrared spectroscopy of the resected nodule in soft tissue revealed that its main constituent was calcium phosphate. The mechanisms for calcification of subcutaneous tissue and basal ganglia are not clear. However, role of tissue injury caused by vasculitis, panniculitis or steroid therapy in subcutaneous calcification, and contribution of vasculitis, microinfarction, or antineuronal antibody to basal ganglia calcification have been proposed. Ectopic calcification of this case may be due to systemic vasculitis and steroid therapy.

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Immune thrombocytopenic purpura (ITP) is infrequent complication and autoimmune hemolytic anemia (AIHA) is, furthermore, a rare occurence in primary Sjögren's syndrome (SjS). This paper reports the first case of SjS associated with both mixed type AIHA and ITP. A 16-year-old female was admitted because of malaise, petechia and nasal bleeding. Laboratory studies revealed anemia (RBC 182×10⁴/μl, hematocrit 17.5%, hemoglobin 5.9g/dl) and thrombocytopenia (platelet 2.7×10⁴/μl). Remarkable agglutination of erythrocytes was seen in blood smear. On bone marrow examination, there was no particular finding except for slight increase of erythroid cells. The serum indirect bilirubin was 4.6mg/dl. The lactic dehydrogenase was elevated. The haptoglobin was less than 10mg/dl. The PAIgG was increased. The titers of antibodies to several viruses and mucoplasma were normal. Direct and indirect Coombs tests were positive for anti-IgG, IgM and C 3 d antisera. The cold agglutinin, identified as IgM, reacted with I-antigen positive erythrocytes with thermal amplitude from 4°C to 37°C. These findings elucidated that hemolysis is caused by both warm and cold autoantibodies. Wassermann's reaction was biologically false positive. However, the concerining of lupus anticoagulant was excluded by cross mixing test and dilute tissue thromboplastin test. The AIHA and ITP were satisfactorily subsided by steroid therapy. Three years later, the patient noticed knee pain and parotid swelling. Any deterioration was not found in peripheral blood. Pathological findings of minor salivary gland was consistent with SjS. The double stain procedure, using monoclonal antibodies, disclosed the reduced proportion of suppressor-inducer T cells (CD 4⁺CD 45 R⁺) and increased proportion of suppressor T cells (CD 8⁺CD 11⁺) in peripheral blood. Frequencies of CD 3⁺, CD 4⁺ and CD 8⁺ T cells were similar as compared with those at the onset of AIHA and ITP. Mantoux's test was negative through the course. These findings suggested that the aberration of suppressor T cells, probably based on subclinical SjS, caused mixed AIHA and ITP and subsequently allowed SjS to appear.

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High-dose gammaglobulin treatment transiently improved the thyroid function in a 49-year-old woman with Graves' disease. She first complained of palpitation and general malaise in October 1986. At that time, purpura occasionally appeared. Her skin was slightly moist. Diffuse goiter without exophthalmus was positive. Anemia was absent. White blood cell and platelet counts were reduced. Total bilirubin (in particular indirect bilirubin) was elevated. In the thyroid function tests, elevation of T 3, T 4, FT 3, FT 4 and thyroglobulin was noted. TSH receptor antibody was positive. TSH was lower than the limit of detection. Both 3-hour and 24-hour ¹²³I uptakes into the thyroid gland were elevated. Thyroid test and microsome test were both positive. Coombs test was negative. Platelet associated IgG was weakly positive. Sternal bone marrow puncture disclosed an elevated megakaryocyte count. Based on these results, she was diagnosed as Graves' disease associated with idiopathic thrombocytopenic purpura or Evans' syndrome. Considering a possible hemorrhagic tendency, she was treated with sulfonated human immunoglobulin for 5 days (17.5g/day). This treatment reduced T 3, T 4, FT 3 and TSH receptor antibody, while it elevated TSH. The 24-hour ¹²³I uptake tended to decrease. However, no change was observed in thyroglobulin, thyroid test or microsome test. Intravenous immunoglobulin may have inhibited the binding of the TSH receptor antibody to the TSH receptors in human thyroid tissue, or may have suppressed the production of the TSH receptor antibody, but the exact mechanism is obscure.

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