Lymphocyte-associated immunoglobulin (LAIg) levels in the sera from patients with systemic lupus erythematosus (SLE) were quantitatively measured by means of enzyme-linked immunosorbent assay (ELISA). The relation between LAIg and SLE activity was studied. The LAIgG levels in a group of sera from untreated patients were significantly higher than those in another from treated ones. As to LAIgM, however, there was no difference between the two groups. There was a significant correlation between the serum levels of complement (CH₅₀) and LAIgG, but no correlation between the levels of CH₅₀ and LAIgM. The levels of LAIgG significantly correlated with those of immune complex (IC) in non-inactivated sera. After inactivation of the sera, the correlation between the levels of LAIgG and those of IC disappeared, while a significant correlation between the levels of LAIgG and those of CH₅₀ remained. There was no correlation between titers of cytotoxicity tests and the levels of LAIgG. LAIg detected by ELISA may contain different kinds of antilymphocyte antibodies from those detected by cytotoxicity test. The serum LAIgG may play some roles in pathogenesis of SLE, since its level correlates strongly with the serum level of complement, one of the representative indicators for the SLE activity.

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The cellular mechanism of anti-nRNP antibody synthesis in patients with systemic lupus erythematosus (SLE) was studied by nRNP-specific solid-phase radioimmunoassay.
Spontaneous in vitro anti-nRNP antibody synthesis by lymphocytes from immunodiffusion determined anti-nRNP antibody positive, anti-Sm antibody negative (anti-nRNP positive) SLE patients were significantly higher than by those from the controls. In addition, similar amounts of anti-nRNP antibody were synthesized spontaneously in both active and inactive stage. The reconstitution experiments revealed that B cells and T cells from anti-nRNP positive SLE must cooperate to synthesize anti-nRNP antibody whether with nRNP stimulation or not. Accordingly, B cells and T cells may be activated in vivo due to unknown causes, and anti-nRNP antibody synthesis in response to nRNP was T-cell dependent.
T₈ cells from anti-nRNP positive SLE patients could suppress anti-nRNP antibody synthesis by autologous B cells, and in correlation with amounts of anti-nRNP antibody synthesized by their whole lymphocytes, their T₄ cells could enhance anti-nRNP antibody synthesis by autologous B cells in response to nRNP. These results indicate that elevated anti-nRNP antibody synthesis in response to nRNP in patient with anti-nRNP positive SLE is due to the abnormality of T₄ cells, and hyperactivity of nRNP reactive T₄ cells may, in part, be responsible for deficient regulation of anti-nRNP antibody synthesis. These findings may lend further insight into understanding of various immunoregulatory defects in SLE.

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Investigations of regulatory helper and suppressor T cells in the in vitro anti-DNA antibody synthesis in NZB×NZW (B/W) F₁ hybrid mice were initiated by the development of an in vitro system in which G 10-passed B cells from B/W F₁ mice were cocultured with mitomycin C-treated T cells in the presence of concanavalin A and either presence or absence of lipopolysaccharide. It was revealed that each IgG and IgM anti-DNA antibody synthesis was under the regulation of separate L3T4⁺ helper and Ly2⁺ suppressor T cells. The function of these class-specific regulatory T cells was age dependent. While the helper effect of L3T4⁺ T cells on IgG antibody synthesis increased, the effect of L3T4⁺ T cells on IgM antibody production decreased in B/W F₁ mice with aging. The IgG anti-DNA antibody production in the cocultures of L3T4⁺ T cells and B cells was suppressed by addition of Ly2⁺ T cells from young but not aged B/W F₁ mice, whereas the production of IgM anti-DNA antibodies was suppressed by Ly2⁺ T cells from aged, but not young B/W F₁ mice. It was also found that although IgM anti-DNA antibody producing B cells were already present in 2-mo-old mice, B cells producing IgG antibodies under the influence of L3T4⁺ T cells appeared in mice at 7 months of age. These data clearly indicate that separate class-specific regulatory T cells are involved in the production of each IgM and IgG anti-DNA antibodies and that the total serum level of the antibodies is reflected by both their age-associated changes and the generation of antibody-forming B cells in B/W F₁ mice.

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To investigate the immunomodulating capacity of monocyte-macrophage system cells (Mφ) in cancer patients, we prepared an in vitro assay system for interleukin-1 (IL-1) and prostaglandin E (PGE) which are produced and released by these cells. Using this assay, we observed the changes in the Mφ capacity in accordance with the progress of the cancer, and also investigated the Mφ cell surface Ia antigen positive ratio (Ia ratio) with activated Mφ as an index. The results indicated that the Mφ in healthy control showed peak values of IL-1 and PGE production and the Ia ratio on the 3rd day of incubation, which means that both IL-1 and PGE were released simultaneously with the activation. IL-1 production and the Ia ratio decreased as the cancer progressed. However, PGE production tended to be less than that in healthy control in patients in the early stage of cancer, but markedly increased in cases of advanced cancer. Therefore, it was clear that the T-cell activating capacity of Mφ is comparatively well maintained in early cancer cases, but is greatly decreased in advanced cases. To observe the effects of cancer patients' serum on the Mφ capacity, Mφ of healthy control was preincubated in the serum of advanced cancer patients, and IL-1 production and the Ia ratio decreased, while PGE production markedly increased. Therefore, it was assumed that immunosuppressive factors in the serum of cancer patients inhibited the presentation of Ia antigen on the Mφ cell surface, and this resulted in suppression of the capacity.
From the above investigations, one aspect of the immunodeficient condition in cancer patients became clear, and it appeared that when non-specific immunotherapy is considered, consideration should also be given to the suppression of PGE secretion as well as increases in IL-1 production in Mφ.

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Granules were isolated from sonicated rat mast cells on a Percoll gradient. Because of an abundant protease activity in rat mast cell granules, the granules were incubated with DFP and PMSF for 1 hour at 30°C and then incubated with [γ ³²P] ATP and Mg²⁺ for 3 minutes at 30°C in the presence and absence of calcium-activated, phospholipid, diacylglycerol-dependent protein kinase (protein kinase C) from RBL-1 cell. After stopping the reaction, SDS/PAG electrophoresis was performed and autoradiographs were prepared to determine the incorporation of ³²P into proteins. Granules incubated with protein kinase C yielded a radioactive band at 28K that was not seen with RBL-1 cell protein kinase C alone or granules without protein kinase C. ³²P incorporation into the 28K band was not affected by TCA and acetone treatment. Iodinated protein kinase C was incubated with DFP and PMSF pretreated rat mast cell granules and analysis in SDS/PAG electrophoresis showed no effects of the granules on the iodinated bands of protein kinase C. These findings suggest that 28K protein in rat mast cell granule membrane may be a substrate for protein kinase C.

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We investigated the relation between polyclonal B cell activation and B cell derived B cell stimulatory factors (BSF) in patients with systemic lupus erythematosus (SLE). B-BCGF activity and IL-1 activity were detected in SAC stimulated B cells supernatant. No significant difference in BCGF-like activity was observed among the active SLE group, inactive SLE group and normal subjects. BCDF-like activity, however, was higher in the active SLE group than the inactive SLE group and normal subjects. Furthermore, IL-1 activity in the active SLE group was also higher than in the other two groups. Anti-human IL-1 antibody inhibited BCGF-like and BCDF-like activity. The inhibition rate was highest in the active SLE group. These results suggested that IL-1 production by SAC stimulated B cells was much higher in active SLE than in inactive SLE, and (that) IL-1 could act as inducer of antibody production. B cell derived IL-1 may be involved in polyclonal B cell activation. As B cells of some patients in the active SLE group spontaneously produced IL-1 and B-BCGF, we speculated that B cells had already been activated in vivo.

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In this study, the in vitro effect of niphedipine as a calcium channel blocker on human natural killer (NK) activity was examined. NK activity against K562 cells was inhibited depending on the dosage of niphedipine added in vitro (it was remarkably inhibited at the concentration of 3.6 × 10³ ng/ml), but it was not inhibited after preincubation of effector cells with niphedipine. Kinetic studies of the effect of niphedipine on NK activity showed that niphedipine depressed the early events of NK cytolysis.
In vitro adding of interferon-α (IFN-α) restored the NK activity depression by niphedipine, and the augmentation of NK activity after preincubation of effector cells with IFN-α was not inhibited by niphedipine.
These results indicate that calcium ions play an important role in the mechanisms of NK cytolysis but suggest that augmentation of NK activity by IFN-α in a part of this mechanism may be developed without Cat²⁺ as a second messenger.

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A 46-year-old male was admitted for evaluation of hepatic dysfunction and bloody diarrhea on January 1986. Physical examination at that time disclosed icterus of palpebral conjuctiva and increased borborygmus in the left iliac region. When admitted the following laboratory examination values were noted: total bilirubin 2.6mg/dl, GOT 392IU/l, GPT 368IU/l, LDH 635IU/l, Al-p 2, 243IU/l, γ-GTP 328IU/l, LAP 363IU/l, total protein 8.2g/dl, γ-globulin 28.5%, ESR 29mm/h, CRP 1+, and occult blood for stool 1+, Barium enema examination showed loss of haustral markings. Diffuse multiple erosions and irregular ulcers were also observed endoscopically. Endoscopic retrograde cholangiogram showed irregular narrowing and dialation of intrahepatic bile ducts and extrahepatic biliary tracts. He had histories neither of biliary calculi nor surgical intervention. From these findings above and clinical courses, primary sclerosing cholangitis associated with ulcerative colitis was diagnosed. Interestingly, following immunological tests showed abnormal values: IgG 2, 431mg/dl, IgM 429mg/dl, positive antismooth muscle antibody, decreased activity of lymphocyte blastogenesis. He responded well to the therapy with prednisolone and salazopyrin. Laboratory examination values on March 1986 improved as follows: total bilirubin 0.6mg/dl, GOT 57IU/l, GPT 132IU/l, LDH 287IU/l, Al-p 622IU/l, γ-GTP 238IU/l, LAP 171IU/l, total protein 6.6g/dl, ESR 7mm/h, CRP-and negative anti-smooth muscle antiboby. This case suggests that abnormal immunological conditions may be involved in the pathogenesis of primary sclerosing cholangitis.

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The effect of fresh frozen plasma infusions was reported for the female child who suffered from hemolytic uremic syndrome at the age of 1 2/12 years and repeated episodes of relapse and recurrence during the following several years.
Her thrombocytopenia in relapse period responded significantly to high-dose intravenous immunoglobulin therapy using Fc intact immunoglobulin.
The latter effects may represent the important suggestion in the interpretation of effectiveness of plasma infusion therapy for the patient with hemolytic uremic syndrome.
The studies were also described on the platelet function, the values of anti thrombin III and complement component of her sera and the metabolism of prostaglandin.

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We treated a Japanese woman who presented symptoms of subacute necrotizing lymphadenitis (SNL), which occurred following an EB virus infection, i.e., infectious mononucleosis (IM). No such cases have been reported and the possibility that SNL may be induced by an EB virus infection has to be given attention.
The patient was a 26 year-old Japanese woman who admitted to Kyushu University Hospital because of persistent fever and sore throat. Systemic lymphadenopathy, hepatomegaly, leukocytosis, an increased number of atypical lymphocytes and the elevation of serum EB VCA-IgM titer were evident and the diagnosis of IM was made. Two months after the onset of IM, she again had a high fever and marked swelling of the left submandibular lymph nodes accompanied by marked tenderness. Serum markers of EB virus showed evidence of the convalescent stage of IM. Leukocytopenia was present and she recovered 40 days later with no specific treatment. Though SNL was not histologically proven, the diagnosis of SNL was made. Immunological investigations showed that the ratio of OKT 4⁺ to OKT 8⁺ lymphocytes was decreased and the natural killer cell activity had deteriorated.

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A 35-year-old woman was admitted, because of xerostomia and a recurrent episode of muscular weakness. Laboratory data showed metabolic acidosis and hypokalemia.
Since keratoconjunctivitis and chronic sialoadenitis were also ascertained, a diagnosis of periodic paralysis in Sjögren's syndrome (SjS) secondary to renal tubular acidosis was made. Furthermore, roentgenogram revealed remarkable calcification of bilateral kidneys. Both periodic paralysis and nephrocalcinosis are very rare complications in SjS. However, it might be reasonable to consider that they are the results of the chronic interstitial nephritis as a part of systemic exocrinopathy caused by autoimmune processes in SjS. The metabolic acidosis and hypokalemia gradually improved by the treatment with prednisolone.

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A patient with rheumatoid arthritis (RA) developed myasthenia gravis (MG) after being treated with D-penicillamine (D-Pc) for 2 years. During the treatment with D-Pc, anti-nuclear antibody turned positive in the serological examination. Anti-DNA antibody and anti-acetylcholine receptor antibody were detected at the admission in our hospital and these titers tended to recede after D-Pc was ceased. Decreased number of peripheral blood B lymphocytes and the low ratio of helper and suppressor T lymphocytes (Th/Ts) (0.67) returned to normal following the discontinuance of D-Pc. Although D-Pc has been known to induce many immunological disorders, in Japan only ten cases with MG and one case with systemic lupus erythematosus (SLE) induced by D-Pc have been reported so far. We have reviewed the literature on these cases including our case.

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