We have established a human B cell line (TKS-1) from the peripheral blood of a patient with rheumatoid arthritis (RA) stimulated with phorbol myristate acetate (PMA). TKS-1 was a monoclonal B cell line, because it expressed surface κ light chain and other surface B cell markers, and had gene rearrangement of κ light chain in its DNA. Furthermore TKS-1 expressed CD 15 antigen, which was known to define human monocytes, granurocytes and Hodgkin's disease. So we investigated whether Leu M1 (CD 15)⁺B cell subset existed in the peripheral blood without any stimulation. CD 15⁺B cells existed in the peripheral blood from three patients with active RA who had complications such as the interstitial pneumonitis and the phlegmone. CD 15⁺B cells disappeared in association with the improvement of clinical symptoms while patients were treated with high or moderate doses of methylprednisolone or prednisolone, however, these cells reappeared at the time of relapsing. CD 15⁺B cells could not be observed in the peripheral blood with other collagen diseases, infectious diseases and interstitial pneumonitis. These findings indicated that CD 15⁺B cells existed in the peripheral blood of some patients with RA.

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The relationship between clinical, laboratory or immunological findings and extra-articular features were studied in 131 rheumatoid arthritis (RA) patients.
(1) The group without extra-articular complications (18 cases, 13.7%); The mean age was more younger, and the mean duration of RA was more shorter in this group. Immunologically, the serum concentrations of complements were highest, compared with those of other groups.
(2) The group of malignant RA (MRA) or with interstitial pneumonia (22 cases, 16.8%); The serum concentrations of C-reactive protein (CRP) and rheumatoid factors (RF) were significantly higher in this group than those of patients without complications.
(3) The group with amyloidosis (17 cases, 13.0%); They were also characterized by increased level of CRP. However, the serum IgG concentration was significantly lower in these cases. Proteinuria and impairment of renal function were observed in 13 (76.5%) and 12 patients (70.6%), respectively.
(4) The group complicated with other collagen vascular diseases such as systemic lupus erythematosus or mixed connective tissue disease (18 cases, 13.7%); This group showed hypocomplementemia and hypergammaglobulinemia frequently.
(5) The group with histologically-proved renal lesions (30 cases, 22.9%); Hematuria was found in 18 patients (60%), proteinuria in 12 (40%), and decreased renal function in 6 (20%). Laboratory examinations revealed lower concentrations of CRP and RF, compared with those of other groups. No significant difference was observed in serum concentrations of immunoglobulin and RF among various nephropathies. These results suggests that the inflammatory and immunological processes may not have significant effects on the development of renal lesions in RA patients.

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In 1970', the presence of soluble histcompatibility antigens in human serum (Ss HLA antigens) was discovered. However it is now still difficult to detect Ss HLA antigen in spite of using the new reported methods. Addtionally the clinical significance of Ss HLA class I antigens are also still unknown. In this report, we detected serum soluble HLA class I antigens in patients with systemic lupus erythematosus (SLE) using the new method of dot blotting, the double determinant enzyme-linked immunoassay with nitrocellulose membrane. The reaction of Ss HLA antigens, peripheral lymphocyte counts, clinical activities of SLE and the clinical course were compared. The results were as follows; 1) Ss HLA class I antigens were positive in 9 cases of 21 cases (42.9%) with SLE. 2) Absolute number of lymphocytes had a negative correlation to the presence of Ss HLA class I antigens in SLE patients (p<0.05). 3) The presence of Ss HLA class I antigen clossely correlated to the activity of SLE (p<0.001). 4) Five of seven active SLE patients in whom Ss HLA class I antigen was not detected, were suffered from nephrotic syndrome due to lupus nephritis. Further studies are needed to determine the pathogenesis of release and clinical significance of serum soluble HLA class I antigen.

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Complement fixation activity of anti-U1 RNP and Sm antibodies was studied by immunoblotting using sera from patients with mixed conective tissue disease (MCTD) and systemic lupus erythematosus (SLE). U1 RNP antigens were purified from rabbit thymus extract by affinity column. The purified U1 RNP antigen consisted of 65 KD, 36 KD, 32 KD, 26 KD, 16 KD and 11-14 KD polypeptides in SDS-PAGE. Anti-U1 RNP antibodies from patients with MCTD and SLE reacted with 65 KD, 36 KD, 32 KD, and 26 KD in immunoblotting.
When the complement fixation activity of antibodies to those polypeptides was tested in MCTD, the antibodies to 32 KD polypeptide showed the significantly stronger reaction compared with the antibodies to 65 KD and 36 KD polypeptides (p<0.01). In SLE patients, antibodies to 32 KD polypeptide showed the same reactivity, moreover complement fixation activity of antibodies to 26 KD and 16 KD polypeptides showed significantly higher (p<0.01) than those to 65 KD polypeptide. In comparison with complement fixation activity of antibodies to U1 RNP polypeptides between MCTD and SLE, the antibodies to 36 KD polypeptide from SLE patients showed higher activity than that from MCTD patients (p<0.05).
Those results suggest that anti-U1 RNP antibodies from MCTD and SLE patients may have different pathogenetic roles in relation to its complement fixation activity.

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In this report we describe the effects of IFN-γ on IL 2 receptor (IL 2 R) expression in peripheral blood monocytes from childhood acute leukemia patients.
1: IFN-γ had an enhancing effect on IL 2 R on monocytes.
2: IL 2 R expression on monocytes incubated in medium alone was more pronounced for patients, but on monocytes incubated in medium with IFN-γ was more pronounced for healthy adults.
3: The enhancing effect of IFN-γ on IL 2 R expression was reduced by more than 1×10^-8mol/L 6-MP but MTX or 6-MP itself does not have any effects on IL 2 R expression.

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Antibodies to phosphorylcholine (PC), as one of the marker of specific antibody, in patients with systemic lupus erythematosus (SLE), multiple myeloma and in cord blood as well as in normals were measured with ELISA. Both IgG and IgM anti-PC antibodies were detectable in the serum from normal individuals. In the serum from SLE which commonly manifests polyclonal hyper-gammaglobulinemia, high concentration of anti-PC antibodies in both classes were observed (28% in IgG class and 16% in IgM, respectively). In the serum from multiple myeloma patients which usually show decreased normal residual immunoglobulines, both classes of anti-PC antibodies were also decreased. In the cord serum which is considered that only the maternal IgG can be transmitted through placenta, not only low concentration of IgM but also low concentration of IgG anti-PC antibodies were observed unexpectedly. At the cellular level, the frequency of B cell precursors specific for PC increased 6-folds after stimulation with pokeweed mitogen (PWM) in normal peripheral blood lymphocytes (PBL). On the other hand, the frequency of PC specific B cell precursor in SLE patients slightly decreased after stimulation with PWM. At the moleculer level of immunoglobulins, anti-PC antibodies from both normals and SLE did not express T15 idiotype which is the most common idiotype of murine anti-PC antibodies.

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As a result of an inquiry into the diagnostic value of flow cytometry and immunohistochemical staining, we retrospectively investigated cell antigens in 27 specimens of lymph node tissue with T cell lymphoma and 22 cases of reactive lymphadenitis. Using flow cytometry, the mean positive rate of the immunophenotypes in T cell lymphoma and reactive lymphadenitis were CD 3 (58.7%, 68.1%), CD 4 (46.9%, 49.8%), and CD 8 (23.3%, 24.7%), respectively. This meant that both conditions showed approximately the same positive rate. As regard to the CD 4/CD 8 ratio, the ratio was 2.01 and 3.31 and it was therefore difficult to diagnose T cell lymphoma as such by only flow cytometry except in two cases of CD 8-positive T cell lymphoma. The immunohistochemical staining confirmed that the tumor was histologically localized and staining of the tissue showed clonal excess of the T cell antigen or CD 4 or CD 8. Therefore this method was found to have a higher diagnostic value.
The cutaneous immunohistochemical staining established positive T cell clonality in 9 out of 17 skin tissue specimens. These consist of seven cutaneous T cell lymphomas and two peripheral T cell lymphomas with cutaneous involvement.
The above result suggests that immunohistochemical staining may prove to be a better modality than flow cytometry in diagnosing lymph node and cutaneous T cell malignancies.

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A hybridoma cell line producing monoclonal antibody was produced by fusing mouse myeloma cell line with spleen cells from BALB/c athymic nude mouse immunized with a human gastric mucinous adenocarcinoma. Immunization was performed by transferring immunocompetent mouse spleen T cells into the athymic mice bearing the human gastric cancer xenograft. After the xenograft was reduced, hybridomas were established by fusing the spleen cells of the mice with P3X63Ag8.653 cells. Screening was performed by immunohistochemical methods.
MKS-1 immunohistochemically reacted with gastric cancers (the antigen detected in 20 of 32 cases) and colorectal cancers (6 of 10 cases) on frozen sections by Avidin-Biotin-Peroxidase Complex methods. On the other hand, it did not react with normal tissues of stomach or colon. The molecular size of antigen recognized by MKS-1 was estimated as around 70kDa by immunoblotting.
These observations suggest that the antigen recognized by MKS-1 may be relatively associated with gastrointestinal cancer cells.

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A familial occurrence of progressive systemic sclerosis (PSS) in an elder sister and CREST syndrome in a younger sister was reported. The elder sister noted Raynaud's phenomenon at 53-year-old. When she was reffered to Katta Municipal Hospital in January 1983 at 61-year-old, she had Raynaud's phenomenon, proximal scleroderma, digital pitting scar, systemic hyperpigmentation and paralytic ileus. She had anti-nuclear antibody and anti-Scl 70 antibody. She was diagnosed as PSS and treated initialy with prednisolone at 40mg/day and later along with D-penicillamine at 100mg/day. The younger sister noted Raynaud's phenomenon at 30-year-old in 1954. On admission to our Hospital in September 1990, she was noticed to have Raynaud's phenomenon, sausage-like swelling of fingers and positive anti-centromere antibody along with anti-mitochondrial antibody. She was diagnosed as CREST syndrome based on her additional symptoms of calcinosis, esophageal dysmotility and telangiectasia.
Eighteen cases of familial occurence of PSS have been reported in the international literature in the world and 2 familial cases in Japan. In this report, two sisters, one PSS and another CREST syndrome were presented. Their HLA haplotype were A 24 (9), Bw 52 (5), DR 2/Bw 54 (w 22), DR 4 in PSS and A 24 (9), Bw 52 (5), DR 2/A 31 (w 19), B 51 (5), DRw 8 in CREST syndrome.

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A 35 years old female had been treated with steroids for bilateral scleritis. High fever appeared 9 months later since the onset of scleritis. Proteinuria, hematuria and elevation of serum creatinine were pointed out and she was sent to our hospital because of rapid deterioration of renal function. Renal biopsy revealed crescentic glomerulonephritis. There was no finding of necrotizing vasculitis nor granuloma. Anti-human neutrophil cytoplasmic antibody (ANCA) was strongly positive in cytoplasmic pattern on admission, and then she was diagnosed as Wegener's granulomatosis (WG). Methylprednisolone pulse therapy combined with anti-coagulant and anti-platelet agents was effective in improving of renal function and clinical symptoms. ANCA became negative one month later together with clinical improvements. Eye involvements as initial symptoms of WG have been reported in only 4 cases. She manifested rapidly progressive glomerulonephritis following scleritis 9 month later without typical respiratory tract involvement. This clinical course was considered as a rare case for WG. ANCA was considered to be a very useful tool for diagnosis and treatment of WG.

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We reported a case of acquired hypogammaglobulinemia with thymoma (Good syndrome). The case is a 67 year-old female, who has suffered from reccurent infections such as flu, diarrhea, and pneumonia, since 1985. In Feb. 1989, she was diagnosed as having oral candidiasis. At that time, hypogammaglobulinemia and thymoma were also pointed out. Immunologic studies revealed marked decrease of circulating B cells and relative increase of T cells. The low ratio of CD 4⁺ cells/CD 8⁺ cells was also noted. T cells obtained from the patient possess inappropriate suppressor activity against immunoglobulin (IgG) production in cell-mixing experiments carried out in a PWM-driven immunoglobulin (IgG) assay system. These findings may explain the cause of hypogammaglobulinemia in this case. Thymectomy was performed in Jan. 1990. However, increase in the level of immunoglobulin is not apparent by the time of this report.

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Neurological symptoms of neuro-Behçet' disease are varied. But among them diplopia is rare. We describe a rare case of neuro-Behçet's disease that neurological lesions in paramedian pontine reticular formation (PPRF) showed concomitant strabismus and diplopia. In 1975 a 25-year old male developed recurrent oral aphthae, painful genital ulcers, and acne-like skin lesions on his face. In 1982 he felt impairment of visual activity. Diagnosis of Behçet's disease was made and colchicine therapy was started. In 1988 he abruptly developed fever, headache and diplopia, and he was hospitalized. The left eye was deviated to the right and movements of both eyes to the left were limited. Other neurological symptoms were not observed. Neurological examinations revealed that diplopia wasn't due to cranial nerve palsy but CNS Behçet's lesions in PPRF. But lesions in PPRF were too small to detect by brain CT and MRI. After corticosteroids therapy diplopia was disappeared.

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We described a case of lupus anticoagulant positive SLE who showed abnormality of EEG, three times syncope attacks and the brain infarction.
A 42-year-old female was diagnosed as SLE in 1981 and has been received administration of prednisolone for 8 years. Because she had syncope attacks three times since November 1988, she was admitted to our hospital on May, 1989. Lupus anticoagulant as well as anti-cardiolipin antibodies was positive. EEG findings suggested a partial seizure attack.
Following pneumonia, she was suffered from brain infarction on October 17, 1989. In this case, it is suggested that lupus anticoagulant may relate to syncope attacks, EEG abnormality and brain infarction.

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