The light chain-type composition of RF, anti-DNA antibody and other immunoglobulin were examined by means of micro ELISA method. The results showed that the κ/λ ratio of RF were highly valiable (0.6-45) in contrast with the relatively constant κ/λ ratios of anti-ds-DNA antibody (1.2-5.0), anti-ss-DNA antibody (1.0-4.0) and anti-tetanus toxoid antibody which were similar to the ratio of serum immunoglobulin. And the κ/λ ratio of RF showed positive correlation with the titer of IgM-RF.
The polyclonal activation of B cells apparently participates in the development of autoimmunity. But our results suggest that RFs may not be produced only by polyclonal B cells activation though anti-DNA antibody may produced as the result of polyclonal B cell activation alone. The affinity maturation may take a part for the production of RF in the patients with long-lasting rheumatoid arthritis.

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There were many studies on antibody-dependent cell-mediated cytotoxicity (ADCC) and natural killer (Nk) cell activity of human peripheral blood lymphocytes. These activities have been recognized to be the important defence mechanisms of our bodies against tumors and viral infections. The changes of both activities of lymphocytes were studied in children with measles virus infection, which was one of the fatal viral infection of young or immunosuppressed children. No significant change was observed in the infected cases without serious complications. In the ones with pneumonia, however, ADCC and NK cell activity were found to be significantly decreased in the “rash”period and to be returned to normal in the “convalescene”.
These results could suggest the possibility that serious complications might occur when ADCC and NK cell activity of lymphocytes as well as T-cell mediated cytotoxicity were decreased and/or depressed in measles virus infection.

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In this study we intended to Characterized the Ia-antigen positive (Ia⁺) T cells in peripheral blood from normal individuals, detecting by indirect antiglobulin rosetting assay utilizing monoclonal anti-human DR antibody, which reacted with the human DR antigen framework.
Higher percentage of Ia⁺ T cells than those described previously by using indirect immunofluorescence was observed in normal peripheral blood. After PHA, Con A or PWM activation, the proportion of Ia⁺ T cells increased up to about 30% of T cells. It also rose rapidly after inoculation with PPD in sensitized individuals only. The proportion of Ia⁺ T cells well correlated with the proportion of T_r cells. It was also revealed that Ia⁺ T cells were enriched in the OKT⁺₄ cell-rich population than OKT⁺₈ population from T cells of normal unstimulated individuals.

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Polymyalgia rheumatica (PMR) has been a rare rheumatic disease in Japan, although it is common in European and American Caucation. But since the first report, PMR is one of well established rheumatic diseases. We report three cases consisting of 46-year-old male, 76-year-old female and 36-year-old female with PMR in our hospital for two years. All of them presented with clinical manifestations of myalgia involving mainly proximal areas of trunks, gait disturbance, and fever of unknown origin refractory to antibiotics. None of them showed abnormalities on physical and roentgenological examinations, EMG, and brain angiography. Laboratory data were summarized as follows; normocytic anemia, remarkably increased erythrocyte sedimentation rate, strongly positive CRP, and negative PPD skin tests. Autoantibodies including anti-DNA antibody, anti-ENA antibody, ANF, LE cell and rheumatoid factors were all negative. Cryoglobulin was positive in one of them, which is seldom reported in the literature. The possibility of association with temporal arteritis was excluded on the basis of clinical signs and symptoms, or angiography.
As to the therapy, all of them responded well to corticosteroid (prednisolone) with prompt disappearance of myalgia and fever, normalized erythrocyte sedimentation rate, and made favorable progress in a maintenance dose of 5 mg daily.

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As an application of Immunobeads, which are the synthetic polyacrylamide particles coated with anti-human immunoglobulin antibodies, the authors have improved Lee's method to a new micro technique to identify and enumerate human T and B lymphocytes simultaneously. Only 1 ml of heparinized blood is required as a specimen.
The principle is based on the reaction of lymphocytes attached onto a plastic microplate with SRBC and immunobeads. The key point of this technique is the order of the addition of the two reagents, at first Immunobeads and then SRBC, otherwise the number of B cells will be much affected. The optimum conditions for this technique were established including the concetration and the volume of lymphocytes and reagents, reaction time and temperature.
The improved, micro and simultaneous method showed a good coincidence with single rosette assay with SRBC, anti-Ig immunofluorescence and Immunobeads assay on 13 healthy normal lymphocytes. It is simple, easy to perform and clear-cut, resulting very few dublerosette cells.

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Selective IgA dificiency can be detected about 0.006% of the population of blood donors in Japan. The deficiency can often be associated with autoimmune disorders. We haveexamined in vitro immunoglobulin synthesis in a SLE patient with IgA deficiency.
The patient, a female aged 31, had high fever and polyarthralgia at the age of 20-year-old and since then she has been taking medicine at intervals. During this period, she has been suffered from tonsillitis, appendicitis, otitis media and pneumonia. The patient was hospitalized under the diagnosis of SLE. The quantitative immunoglobulin levels were IgG 2190, IgA O, IgM 269 (mg/dl). Peripheral lymphocyte counts were normal and T: B ratio was 65: 35. Immunofluorescent examination revealed that Ig bearing cells were present in normal number on peripheral blood smear.
Immunoglobulin biosynthesis in the patient's peripheral blood lymphocytes was measured in vitro. As a consequence, IgG and IgM were synthesized at a normal level, but IgA at an extremely low rate. Co-culture of T cells from normal and B cells from the patient resulted in reduced synthesis of IgA, and moreover combination of the patient T cells and normal B cells also resulted in reduced synthesis of IgA. However co-culture of X-ray irradiated T cells from the patient and B cells from normal resulted in sufficient production of IgA. Thus, pathogenesis of IgA deficiency in the patient was demonstrated to be due to B cell insufficiency and hyperfunction of suppressor T cells.

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Proliferative responsiveness of B cells from 7 patients with primary immunodeficiency was studied. The used mitogens were F (ab')₂ fragment sheep anti-human IgGF (ab')₂ fragment (ã-IgGF(ab')₂), Staphylococcus aureus Cowan I (STA) and Epstein Barr virus (EBV). The results obtained are as follows.
1) In common variable hypogammaglobulinemia (3 cases), B cells from 2 patients showed markedly decreased responses to all the used mitogens, while those from one patient showed normal responses. The decreased responses to mitogens were not restored by depletion of adherent cells.
2) In IgA-deficiency (2 cases), B cells from one patient associated with juvenile rheumatoid arthritis showed decreased responses to all the mitogens, while those from the other showed normal responses.
3) In immunodeficiency with hyper IgM (one case) and IgM-deficiency (one case), the mitogen responses of B cells were almost normal except the slight decreased response to STA.

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The immunological deficiency of multiple myeloma is characterized by reduced levels of serum normal immunoglobulins. However, the mechanism is not completely understood. The present study deals with the suppressor activity of monocytes from patient with myeloma which prevent the maturation of normal B cells into immunoglobulin-producing cells.
When monocytes from patients with myeloma were added to normal lymphocytes in the presece of pokeweed mitogen the immunoglobulin synthesis of the normal lymphocytes was suppressed. The suppressor effect of the monocytes was not dependent on the methods which monocytes were isolated. Monocytes from patients withmyeloma showed the almost same characterization as those from normal individuals.

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A simple and rapid Microenzyme-Linked Immunosorbent Assay (MELISA) has been developed for determination of anti-single and anti-double stranded DNA antibodies in humans using a combination of protain A-alkaine posphatase conjugates and single or double stranded DNA (ss or ds DNA)-coated polystyrene microplates. After 1 h treatment of the plates with 100 μl of poly-L-lysine (PLL) solution (50 μg/ml), an aliquot of the solution containing 100 ng ss or ds DNA (50 μl) was added to PLL-treated plates and evaporated at 37°C overnight to facilitate the adherance of ss or ds DNA to the plates. None specific binding of diluted test sera from patients with systemic lupus erthematosus (SLE) or from normal individuals to the PLL-coated plates was minimized by exposure of the plates for 1 h to Trisbuffered saline (pH 7.4) containing 0.01% bovine serum alubmin.
The present assay is advantageous over those reported so far as it saves time and antigen. Results are as followed: anti-ss DNA antibodies in SLE by MELISA were significantly higher than those of rheumatoid arthritis (RA) and of normal individuals, but no difference was seen between those of SLE and chronic active hepatitis (CAH), whereas anti-ds DNA antibodies in SLE were significantly higher than those of RA, CAH and normal individuals.
Correlation between antibody titers obtained by MELISA and by radioimmunoassay showed positive. Patients with SLE were devided into four groups: 1) patients with no complications, 2) patients with nephritis, 3) patients with central nervous system (CNS) disorder with convulsion and/or cerebrovascular lesion (CNS lupus, type I), and patients with psychosis (CNS lnpus, type II). Anti-ss DNA antibody titers among these four groups were of no significant difference, however anti-ds DNA antibody titers in the group of CNS lupus, type I were significantly higher than those of the others.

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A 7 month-old-boy with severe combined immunodeficiency suffered from cough, diarrhea, and intractable candidiasis, and died of a respiratory failure by giant cell pnemonia at 13 month-old. Immunological studies revealed low numbers of T cells, poor responses of his lymphocytes to mitogens, and markedly increased levels of surface immunoglobulin bearing cells. Serum concentrations of IgA and IgM were normal and IgG was high with M component, but functional antibody responses were absent. A plasma cell was absent in bone marrow and lymph nodes at autopsy. It was suggested that the maturation of B cell to plasma cell was impaired.
In addition, a tumor was found at his left upper arm on admission. The biopsy revealed that the tumor was a lymphoproliferative disease and consisted of the cells resembled mature lymphocytes. None of cells formed E rosette and had the surface immunoglobulin. The tumor cells infiltrated the muscles and fractured the left humerus. However, the tumor regressed spontaneously. At autopsy, the tumor was not found at the left upper arm but a solitary tumor with lymphoproliferation was found in the liver. It can not be denied that transfer factor and transplanted fetal thymus had an effect on the tumor regression. It is suggested that the tumor was not malignant but a monoclonal lymphocyte proliferation responsed to certain stimuli. Transplantations of the fetal thymus and the liver were unsuccesful in restoring immunity.

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Three patients with advanced rheumatoid arthritis developed fatal pancytopenia in one case and fatal agranulocytosis in the other two, during the course of D-penicillamine therapy.
One patient with classical rheumatoid arthritis experienced fatal pancytopenia after four year treatment of 600mg/day of D-penicillamine which had successfully inhibited acute arthritic episodes during that time. Without any abnormal data suggestive of blood crisis in routine peripharal blood analysis, the patient had begun to complain of palpitation and arrhythmia. The later blood count revealed severe anemia (Hb 6.2g/dl)with leukopenia (2100/mm3) and no platelet. Every effort of suporting therapies including transfusions of fresh blood and platelets, injections of high doses of corticosteroid and protection against life-threatening infections seemed to be of no value for improvement of his pancytopenia and for sequential severe infections. He died from asphyxiation in air way bleeding after two months of hospitalization.
The other two patients with classical rheumatoid arthritis experienced sudden catastrophes similar to the condition of sepsis with agranulocytosis. Until the attaks of high fever and acute arthritis, they had been treated with 400mg/day or 200_??_300mg/day of D-penicillamine only for one month with no beneficial effect for their arthritis. They were immediately hospitalized and were found to have leukopenia with little evidence of anemia and thrombocytopenia in their peripheral blood.
On the second day in the hospital, agranulocytosis was seen without any changes of platelet and erythrocyte counts and was continued till the sixth day when they died from cerebral bleeding and septic shock respectively.
Our three patients were characterized to possess advanced arthritic lesions, severe infections at the time of fatal blood disturbance and relatively heavy doses of anti-rheumatic drugs including corticosteroids, gold and non-steroidal anti-inflammatory drugs before the start of D-penicillamine. These suggest that our patients had been already suppressed hemopoiesis in bone marrow presumably due to several causes including rheumatoid arthritis itself and medications other than D-penicillamine. In addition, adrenal insufficiency caused by long use of steroid may play a role in sudden onset of severe infections which may result in further consumption of leukocytes. As known to have direct cytotoxic effect on bone marrow or to trigger the immunological reactions toward elimination of leukocytes and other cells, D-penicillamine may further suppress the bone marrow functions enough to be realized by routine blood analysis.
Althouth our data of three patients are not enough to elucidate the mechanism of marrow suppression or leukopenia by D-penicillamine, learning of rare cases with fatal pancytopenia or agranulocytosis during D-penicillamine therapy may be important for revaluation of the drug and also general clinics of patients with rheumatoid arthritis.

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