Binding of the purified anti-nRNP antibody and it's F (ab')₂ fragment obtained from serum of a patient with mixed connective tissue disease to the normal human peripheral blood lymphocytes was studied flowcytometrically using fluorescence activated cell sortors.
In flowcytometer, T cells were identified by PE-conjugated anti-Leu l antibody and binding of the antibody was identified by FITC-conjugated anti-human IgG antibody.
The IgG fraction of anti-nRNP antibody bound mainly to the non-T cells, that is B cells.
When the anti-nRNP antibody was treated by pepsin to prepare F (ab')₂ fragment of the antibody, the binding to lymphocytes was extremely reduced.
In addition, when the lymphocytes were treated by aggregated rabbit IgG, the binding of anti-nRNP antibody (IgG) was scarecely noted.
These results suggested that anti-nRNP IgG could bind to non-T, mainly B cells, through Fc receptors of lymphocytes.

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Eight patients with subacute necrotizing lymphadenitis have been studied. All the patients showed the persistent cervical lymphadenopathy with tenderness and the subacute illness with low-or high-grade fever. Characteristic pathological findings, which consist of the immunoblast and histiocytoid cell infiltrations around necrotic regions at paracortical areas of affected lymph nodes, were observed in the excised lymph nodes from 8 patients. Peripheral blood mononuclear cells obtained from patients and controls were examined about the proliferative responses to phytohemagglutinin, concanavalin A, anti-CD 3, pokeweed mitogen, PPD, and candida antigen, and natural killer cell activity. In the report, it was demonstrated that the proliferative responses to those mitogens and recall antigens are highly depressed in patients' peripheral blood mononuclear cells, compared to controls'. Natural killer cell activity is also decreased in patient group and CD 16 positive cells are significantly fewer in patients' peripheral blood mononuclear cells than in controls'. When peripheral blood mononuclear cells were stimulated with Epstein-Barr virus and immunoglobulins produced by B cells were assessed, it seemed that immunoglobulin production from B cells of patients stimulated with Epstein-Barr virus was fairly preserved, compared with the prolifer-ative responses to mitogen of T cells or natural killer cell activity.

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The effect of IFN-γ on mouse IgG 1 CD 3 monoclonal antibody (VIT 3 b)-induced proliferation of peripheral blood mononuclear cells (PBMC) was examined by determinants with ³H-thymidine uptake.
In the presence of IFN-γ, VIT 3 b-induced proliferation was enhanced and this effect was more prominent in cells with lower responsiveness to VIT 3 b. However, the maximum enhancement by IFN-γ was about 300% of that in the absence of IFN-γ. VIT 3 b-induced proliferation depended on the concentration of monocytes, but even with less than 5% monocytes, enhancement by IFN-γ was observed.
The effect of IFN-γ was lower in patients with ALL than in healthy adults.

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We surveyed development of cancer in Japanese renal transplant recipients by collecting questionaires from the institutions performing renal transplantation in Japan. A total of fifty-five malignant diseases occurring in renal transplant recipients was reported.
In order to study the effect of immunosuppressive drugs (Pred, AZ, CYA) on the development of malignant diseases in renal transplant recipients, NK and LAK activities of peripheral blood lymphocytes of twenty-one renal transplant recipients receiving those drugs for more than three years were investigated. The NK and LAK activities of renal transplant recipients were significantly lower than those of healthy volunteers or patients suffering from gastric cancer (p<0.01). Both NK and LAK activities of patients receiving Az were significantly lower than those of patients not receiving it. Pred has tendency to suppress NK and LAK activities of renal transplant recipients in dose dependent manner. However, both NK and LAK activities of patients receiving CYA were significantly higher than those of patients not receiving it (p<0.01). Our findings indicate that CYA has less inhibitory effect on NK and LAK activities of renal transplant recipients than conventional drugs (Pred, or Az). It seems that CYA has significant immunosuppressive effect on renal transplant recipients, but it does not impair the host defense mechanism of those patients as much as conventional drugs.

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This study was done to investigate the effect of tuberculosis on disease activity of systemic lupus erythematosus (SLE).
Out of 231 patients with SLE who were admitted to our hospital between 1979 and 1988, five patients (2.2%) developed tuberculosis. No remarkable changes of disease activity of SLE were found by the development of tuberculosis in 3 patients. However, clinical and immunological improvement of SLE was found in two patients after development of relatively severe miliary tuberculosis. These 2 patients showed loss of proteinuria and rheumatoid factor and reduction of antinuclear antibody (ANA) and antiDNA antibody titers, all of which occurred 3 to 6 months after development of tuberculosis. It is suggested that severe miliary tuberculosis could modify or improve SLE as mycobacterium tuberculosis has diverse effects on the host immune state.

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The ability of B-cell chronic lymphocytic leukemia (B-CLL) cells to present antigen was investigated in order to define the multiple cell lineages of human antigen-presenting cells and to determine the relationship between antigen-presenting capacity and the amount of HLA class II antigen on the B-CLL cell surface. Furthermore, the influence of a phorbol ester, TPA, on B-CLL cells was also studied. The results obtained were as follows:
1) The B-CLL cells demonstrated the ability to present antigen to antigen specific T cell lines.
2) The TPA treatment enhanced the HLA-DR antigen expression on B-CLL cells.
3) The antigen presentation by the B-CLL cells was augmented by the TPA treatment. This augmentation seemed to be related to the enhanced expression of HLA-DR antigen.
4) The antigen presentation of the B-CLL cells was restricted by HLA-DR antigen.
5) The B-lymphoblastoid cell line established from the peripheral blood mononuclear cells of a B-CLL patient showed strong antigen-presentation ability comparable to that of the TPA-treated B-CLL cells.

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In order to study the efficacy of lymphocytapheresis (LCP) in patients with rheumatoid arthritis (RA), LCP was performed in 5 RA patients and its efficacy was compared with that of double filtration plasmapheresis (DFPP) performed in 12 RA patients.
Five RA patients, diagnosed according to the American Rheumatism Association (ARA) criteria, were selected to apply LCP because of their poor responses to the conventional drug therapies, such as non-steroidal antiinflammatory drug, D-penicillamine, and/or prednisolone. They were hospitalized and received LCP once a week for 4 weeks. LCP was performed using newly developed leukocyte removal filter for an hour. Nafamostat mesilate was injected during a procedure as an anticoagulant at 50 mg/hour.
DFPP was performed once a week for 4 weeks in 12 RA patients diagnosed according to the ARA criteria. Two thousand milliliter of plasma was treated and 400ml of removed plasma were replaced with 5% albumin solution during a procedure.
Clinical and laboratory findings were examined before and at 1, 4, and 8 weeks after a series of both treatments. The administration and dosage of medications were held constant throughout the study.
In LCP, 3×10⁹ lymphocytes were removed during one procedure. Percentage of Leu-2 a positive T-cell significantly increased at 4 weeks after LCP, and Leu-3 a/Leu-2 a ratio decreased at 4 weeks after LCP associated with the improvement in clinical manifestations. Platelet count and hemoglobin levels did not change through this study.
In DFPP, complement (CH 50) significantly decreased at 4 weeks after a series of treatment together with the improvement in clinical manifestations in the different mechanism from that of DFPP. And furthermore, LCP is thought to be an effective strategy in treating RA patients because the improvement in clinical manifestations may last longer than DFPP due to the decrease in Leu-3 a/Leu-2 a ratio up to 8 weeks after a series of LCP. Consequently it is worth investigating the efficacy of LCP in longer period.

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We have identified two sera containing anti-liver/kidney microsome (anti-LKM) 1 antibody and 7 sera containing anti-Is antibody among one hundred sixty seven samples taken from patients suspected of having autoimmune hepatic diseases. In this study, we report on the immunological characterization of these two antibodies in relation to each other and to the various antimitochondrial antibodies.
Anti-Is antibody was found to be distinct from any of the previously defined antibodies such as anti-LKM 1, anti-MM, precipitating antimitochondrial antibodies (anti-M-A, anti-M-B, anti-M-C and anti-M-D) when tested by double immunodiffusion using rat liver sonicated mitochondrial and microsomal fractions. Anti-Is and anti-LKM 1 were also found to be different in terms of cellular specificity. When viewed by indirect immunofluorescence, anti-LKM 1 significantly stained proximal tubular cells, hepatocytes, and portal area cells, while anti-Is only slightly stained tubular cells. Furthermore, anti-Is antibody was found to be mostly associated with AMA, while anti-LKM 1 was not. Finally, a monospecific anti-Is antibody immunoprecipitated a complex of 87 kd, 80 kd and 72 kd proteins using ³⁵S-methionine labeled HeLa cell extract. The molecular weight of the LKM 1 antigen was estimated to be 50 kd by western blot under reducing conditions using partially purified rat liver microsomal fraction. Clinical characterization of these antibodies has yet to be conducted.

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We report a 27-year-old female with systemic lupus erythematosus (SLE) and autoimmune hemolytic anemia (AIHA) with a history of pure red cell aplasia (PRCA) 8 years before. The patient was admitted to our hospital because of arthralgia, myalgia, fever and general fatigue on March 30, 1988. She was diagnosed as SLE with AIHA as a result of laboratory examinations which revealed anemia (Hb 6.6g/dl), leukocytopenia, presence of LE cells, high levels of anti-DNA and anti-nuclear antibodies, increased urine urobilinogen, positive Coomb's test and decreased level of haptoglobin. The etiology of PRCA had been attributed to the inhibitory effect of T-lymphocytes on the differentiation of erythroid progenitors rather than humoral factors. Thus, it was of great interest that immunologically different type of anemias developed with a time lag of 8 years in this case.

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A case of polyarteritis nodosa (PAN), in which serous otitis media and scleritis were the initial signs, is reported.
61-year old woman suddenly complained of vertigo and hearing impairment. Diagnosis of serous otitis media was done and she developed the same symptoms several times later. Six months after the first manifestations of aural symptoms, she developed painful red eyes bilaterally and a diagnosis of scleritis was made. Treatment with betamethasone and atropine eye drop was started. During a year of follow-up, a deterioration of her hearing impairment, which was mixture of conductive and perceptive loss, occured. From these findings, atypical Cogan's syndrome was considered though definite diagnosis could not be made for lack of informations around the onset of her illness.
About one and a half years' of her illness, she developed fever, consciousness disturbance and deterioration of ocular symptoms occured, however the involvement of other organs was not apparent. Tentative diagnosis of a “systemic vasculitis” was made. She was treated with oral predonisone 40 mg daily, with improvement in her general condition but without beneficial effect on hearing acuity. Later muscle biopsy was performed and a specimen revealed necrotizing vasculitis. A diagnosis of PAN was made.
Our case seems to be important in considering the correlation between PAN and atypical Cogan's syndrome.

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A case in whom systemic lupus erythematosus (SLE) became evident five years after the appearance of lymphadenopathy and polyclonal hypergammaglobulinemia, is reported. The patient is a 33-year-old woman in whom hypergammaglobulinemia was incidentally pointed out 5 years ago. She had no symptoms and small lymphnodes were detected at the left side of the neck. LE cell phenomenon was negative but anti-nuclear antibody and anti-DNA antibody were weakly positive. Lymphangiography revealed significant swelling of the lymph nodes in the bilateral inguinal and paraaortic regions. Histologically, plasma cell hyperplasia was evident, the finding compatible with idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL). Five years later she developed alopecia, high fever and morning stiffness. LE cell phenomenon became positive and the titers of the anti-DNA antibody and anti-nuclear antibody markedly increased. According to the criteria for SLE of ARA (1982), a diagnosis of SLE was made.
This case represented a subclinical on latent stage of SLE manifested by lymphadenopathy and hypergammaglobulinemia and may give some ideas to consider the mechanisms of the development of SLE.

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