An alteration in the maternal-fetal immunologic function has long been thought as a possible cause of preeclampsia. There are papers reporting that mothers produce antibodies against fetal antigens. Laminin is a basement membrane glycoprotein localized in the trophoblast and glomerulus. In order to investigate specific antibodies in preeclampsia, we attempted to demonstrate anti-laminin antibody and evaluate the relationships between anti-laminin antibody and severity and symptom of preeclampsia, in order to correlate them with pregnancy outcome. Detection of anti-laminin antibodies was performed by the immunoblot method. Thirty three cases of preeclampsia including 3 eclampsia, 10 normal pregnancy and 5 non-pregnant women were the subject of our study. Anti-laminin IgG antibody was detected in 50% of the severe cases, 26% of the mild cases and 67% of the eclampsia. Anti-laminin IgM antibody was detected in 21% of the severe cases, 11% of the mild cases and none of the eclampsia. Neither anti-laminin IgG nor anti-laminin IgM antibodies were detected in normal pregnancy and non-pregnant women. Anti-laminin antibody was found more frequently in cases with hypertention or proteinuria than in cases with edema. In cases which anti-laminin antibody was positive, higher percentages of intrauterine growth retardation (IUGR) and premature labor were detected. High levels of immune complexes were detected in two out of 6 positive cases of antibodies. We found that autoantibody to laminin was detected in both mild and severe types of preeclampsia. And anti-laminin antibody was related to severity and symptoms, such as proteinuria and hypertension of preeclampsia and also to IUGR and premature labor. Anti-laminin antibody may affect the placenta and the kidney and may play a role in the pathogenesis of preeclampsia.

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Using 25_??_75% ammonium sulfate fraction of rabbit thymus extracts (RTE) SS-B/La antigen was purified by anti-SS-B/La affinity column. The antigen contained 53kDa which was reactive with anti-human IgG, as well as 50, 45 and 43kDa reactive with biotinylated anti-SS-B/La. Moreover, 53kDa polypeptide could be completely absorbed from the antigen by anti-human IgG affinity column. Bound fraction of this column had not only 53kDa but also 50, 45 and 43kDa SS-B/La. It suggested that SS-B/La proteins appeared to be separated into two groups from the point of view whether they were complexed with 53kDa reactive with anti-human IgG or not.
Using the antigen after absorbed by anti-human IgG affinity column, ELISA was developped and immunoglobulin classes of anti-SS-B/La were studied. By this method, anti-SS-B/La were positive Sjögren's syndrome (65.4%), SLE (43.4%), RA (12.8%), PM-DM (4.76%) and PSS (35.7%). All classes of antibodies were observed in patients' sera with Sjögren's syndrome more frequently than the others. A different preference for classes of anti-SS-B/La was found in each rheumatic diseases. In SLE with. sicca, IgG class of the antibody was detected more frequently than without sicca, and in RA with sicca, IgM class was dominant. All classes used to be detected simultaneously in sicca alone group.

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To clarify the involvement of complements in the pathophysiology of systemic lupus erythematosus (SLE), we investigated the association of the initial serum complement levels and their serial changes with clinical features in 60 active SLE patients.
Oral ulcer, lupus nephritis, hemolytic anemia, high levels of anti-dsDNA antibody and the presence of immune complex in SLE patients were found to contribute to decreased levels of complements (CH50, C3 or C4). It was also found that the initial levels of complement were significantly depressed in patients who had bacterial infections or aseptic necrosis of femoral head during the course of SLE or who received steroid pulse therapy.
Serial measurement of complement levels disclosed that CH50 levels were similarly normalized during 3 to 6 months of therapy both in the patients with lupus nephritis, who initially showed markedly low levels of CH50, and in those with CNS lupus who initially had slightly low levels of CH50. This suggests that hypocomplementemia in lupus nephritis is not refractory and is normalized with high doses of steroids.
24.3% of the patients remained still hypocomplementemic after 6 months of therapy. These patients had hemolytic anemia or low C4 levels before treatment more frequently than those whose complement levels were normalized.
Further study on the prognosis of the patients with continuous hypocomplementemia will be necessary.

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Most cases of myocardial infarction are resulted from coronary artheriosclerosis. However, distinctive factors for widening or exaggerating the lesions have been still obscured. As one of the factors, complements have been reported, but the precise mechanisms of the complements for myocardial injury have not been elucidated. We reported in this paper that the levels of various complement components and CRP from 11 patients who hospitalized within 24 hours after the onset of heart attack were evaluated, comparing levels of m-GOT which reflected the severity of myocardial injury.
Groups which are classified depend on the serum levels of m-GOT are 1st group (n=25): under 10Ku/ml, 2nd group (n=14): 11-30Ku/ml, 3rd group (n=7): 31-50Ku/ml and 4th group (n=6): over 51Ku/ml.
The levels of CRP were well correlated with the levels of m-GOT. No significant change of the levels of early complement components, Clq and C4, were found. Late complement components, C3, C5, C9, Factor B, P and C3a anaphylatoxin, were increased with elevating of m-GOT, suggesting that the alternative pathway may involve to the myocardial injury. Among the late complement components, particularly C3a anaphylatoxin was closely correlated with level of m-GOT (r=0.706).
These results suggested that the late complement components might be activated in the lesion of the myocardium and exaggerate the lesion.
The measurement of C3a levels of the patients with myocardial infarction is useful for evaluating the severity of the disease.

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A case of mixed connective tissue disease (MCTD), who had aseptic meningitis and severe peripheral neuropathy was reported.
A fifty-years-old female was diagnosed as meningitis and treated with antibiotics and high dose corticosteroid. She was transferred to our hospital because of progressive pericardial effusion and elevation of myogenic enzymes. So anti RNP antibody was positive in her serum and cerebrospinal fluid, that she was diagnosed as MCTD. Pericarditis and consciousness disturbance were improved by corticosteroid therapy, but peripheral neuropathy remained. The histological findings of the sural nerve biopsy showed severe nerve fiber loss, thickening of muscle layer and endothelium of arterioles. In immunofluorescence study, IgM deposition was observed in endoneural interstitium. These findings suggested that humoral immunological mechanisms were involved in the pathogenesis of this peripheral neuropathy.

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A patient who developed liver dysfunction, diffuse skin eruptions, and mucosal lesions after three days of treatment with bucillamine is reported. Consequently, betamethasone was substituted for bucillamine therapy. All symptoms disappeared during betamethasone treatment. Bucillamine alone gives a positive reaction when used as an antigen in drug-induced leucocyte stimulation tests, indicating that bucillamine is probably the agent of the side effects descrived above.
Awareness of the potential for development of side effects should be paid in bucillamine administration, and the initial dose should be less than the currently recommended usual dose of 300mg a day.

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We studied eight cases of primary biliary cirrhosis associated with other rheumatic or autoimmune diseases, who had been followed in our division since 1979 to 1988.
Five cases of Sjögren's syndrome, three cases of rheumatoid arthritis, five cases of progressive systemic sclerosis, one case of CREST syndrome, one case of MCTD and two cases of chronic thyroiditis were included. In this study, all of them had no symptom of primary biliary cirrhosis. Seven cases had elevated serum ALP and IgM levels. Decreased level of serum ALP was observed in two cases treated with thyroxine. It was suggested that thyroxine was of benefit in the clinical course of primary biliary cirrhosis. Laboratory tests showed positive anti-M2 antibody in all cases (100%) and positive anticentromere antibody in four cases (50%).
We conclude that immunological tests such as serum anti-mitochondrial antibody, anti-M2 antibody and anticentromere antibody should be performed in a case with such rheumatic diseases who shows liver dysfunction, and liver biopsy need to be performed to confirm the diagnosis of primary biliary cirrhosis.

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A 16-year-old girl complained of fever, facial erythema and stomatitis, and was admitted to our hospital in June, 1980. The girl, having the onset of epileptic attacks at the age of 12 years, had been treated for 3 years with anticonvulsants. She stopped the drug intake about 6 months before the hospitalization. Laboratory data on admission revealed positive fluorescent antinuclear antibodies (ANA) and anti-DNA antibody, hypocomplementemia and proteinuria (0.6_??_2.5g/day). Under the diagnosis of systemic lupus erythematosus, corticosteroid therapy was started. Thereafter to this therapy, plasmapheresis and the pulse-steroid therapy through intravenous administration daily of 1g methylprednisolone were combined. The treatment improved the urinary protein level, and she was discharged from hospital in June, 1981. From the end of 1983, however, her urinary protein was increased with frequent occurrences of hypoproteinemia associated with edema of the lower extremities. Plasma albumin transfusion was sometimes performed for treating hopoalbuminemia. In late 1985, the patient still had proteinuria, hypocomplementemia and the high ANA titer. Under instructions from her parents, she tapered steroid therapy and started special-diet therapy without our permission: a 1, 200-calorie diet per day, low in protein (30g/day) (especially animal protein) and in animal fat. Thereafter, her urinary protein was decreased. The titer of ANA and anti-DNA antibody was also decreased to the negative level in January 1988; however, hypocomplementemia has still continued. The diet low in calorie and protein, especially low in animal fat and animal protein, could exert beneficial effects on the patient in inhibiting the disease activities.

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Two cases of rheumatoid arthritis (RA) with amyloidosis, causing xerostomia, diagnosed by labial salivary gland biopsy are reported.
Case 1, a 65-year-old female who had been suffered from RA for eighteen years, and congestive heart failure and renal insufficiency for three years, was admitted because of general fatigue and vomiting. Laboratory findings on admission were as follows: the erythrocyte sedimentation rate was 72mm/hour, CRP 12.0 mg/dl, blood urea nitrogen 875 mg/dl, serum creatinine 3.5 mg/dl, RAHA 1:2, 560, antinuclear antibody negative, antibodies to SS-A and SS-B negative, cryoglobulin negative. The urine gave a + test for protein and the sediment normal. On examination she complained of severe xerostomia. Her labial salivary gland biopsy showed deposition of amyloid around salivary ducts and acini. She was diagnosed as secondary amyloidosis in RA. Congestive heart failure, paralytic ileus and renal function became gradually worse, and she died. At necropsy she was diagnosed as generalized amyloidosis.
Case 2, a 64-year-old female who had been suffered from RA for fifteen years, was admitted because of fever and chillness. Laboratory findings were as follows: the erythrocyte sedimentation rate was 45mm/hour, CRP 13.8mg/dl, blood urea nitrogen 27.3mg/dl, serum creatinine 1.4mg/dl, RAHA 1:160, antinuclear antibody negative, antibodies to SS-A and SS-B negative. The urine gave a ± test for protein and the sediment normal. She had no congestive heart failure and no gastrointestinal symptoms in the past. On admission she had renal insufficiency and complained of severe xerostomia. Her labial salivary gland biopsy revealed deposition of amyloid. Renal insufficiency was thought to be due to amyloidosis. Her general condition had been getting better.
Our cases showed that xerostomia in RA might be due to not only Sjögren Syndrome but also amyloidosis, and that labial salivary gland biopsy had proved to be a sensitive method for diagnosis of amyloidosis in RA.

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In this report, we described a 60 year-old man with systemic lupus erythematosus (SLE) who was diagnosed by lymph node biopsy.
He was admitted to our hospital because of fever of unknown origin (FUO). Polyarthralgia and fever developed six months ago. Four months later, he was admitted to hospital because of left hemiparesis. He was diagnosed as multiple cerebral infarction by computed tomography. The laboratory studies revealed elevated erythrocyte sedimentation rate and C-reactive protein (CRP) level, and lymphocytopenia. Two months ago, he was admitted to that hospital again because of high fever. A biopsy of inguinal lymph-node showed the necrotizing lymphadenitis. On admission to our hospital, laboratory examinations revealed lymphocytopenia, marked thrombocytosis (74.5×10⁴/mm³) and elevation of CRP (13, 193μg/dl). But infections and neoplastic diseases were excluded with an extensive work up. He was suspected to have SLE due to the positive antinuclear antibody (640×, homogenous and peripheral pattern), LE cell phenomenon, and Coomb's test.
Re-examination of his lymph-node biopsy specimens revealed the hematoxylin bodies with diffuse paracortical necrosis of lymphofollicules. From these findings, he was diagnosed as SLE. Positive anticardiolipin antibody detected by ELISA and multiple cerebral infarction indicated that he also had complicated antiphospholipid syndrome. Immediately after corticosteroid therapy, fever and abnormalities of the laboratory data including thrombocytosis improved.
Recent advances in immunological examinations have diminished the possibility that patients with SLE will remain undiagnosed as FUO. Futhermore, a tissue biopsy is rarely necessary to establish the diagnosis of SLE. But this patient had several unusual manifestations of SLE, high fever persisting beyond six weeks without specific symptoms of SLE and marked thrombocytosis.
Therefore, this case suggested the clinical diversity of SLE and the importance of Lymph-node biopsy.

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A case of idiopathic portal hypertension (IPH) associated with aplastic anemia is reported. A 67-year-old Japanese woman was admitted to our hospital because of pancytopenia. She had had mild liver dysfunction for eight years. CT scan revealed huge splenomegaly and liver histology disclosed portal fibrosis with preserved lobular structures, which were consistent with IPH. Peripheral blood showed pancytopenia, and bone marrow aspiration disclosed hypoplastic marrow without myelodysplastic changes. Low uptake of the bone scintigram, high serum erythropoietin level and good response to methyl-prednisolone pulse therapy supported the diagnosis of aplastic anemia. It was speculated that immune processes were involved in the pathogenesis of IPH and aplastic anemia. Thus, coincidence of these two diseases may in part be based on common autoimmune mechanism.

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Thirteen serum samples positive for anti-centromere antibodies (ACA) were selected from patients with primary biliary cirrhosis (PBC). Each IgG subclass of ACA was examined by the indirect immunofluorescent method using monoclonal antibody to human IgG subclass. ACA of IgG₁ and IgG₃ subclasses were positive in almost all sera with high titers of more than 1:320. ACA of IgG₂ and IgG₄ subclasses were negative in 6 and 7 out of 13 sera respectively, and the antibody titers in positive sera distributed widely from 1:40 to 1:2, 560. On the otherhand, antibodies to mitochondria (AMA) which often coexisted with ACA distributed similarly in the four subclasses.
In this study, we could not find any significant correlation between IgG subclass distribution of ACA and clinical features of PBC. However predominant restriction of ACA to IgG₁ and IgG₃ subclasses could speculate some pathogenetic abnormalities behind PBC.

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[in Japanese]

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We introduced a simple method of cDNA cloning for variable regions of monoclonal antibodies which consists of amino acid micro-sequencing with the PVDF membrane (Immobilon-P^TM) and reverse transcriptase-PCR followed by subcloning into plasmid and double stranded sequencing. The PVDF membrane and PCR made it possible to skip the procedures for extraction of protein from the electrophoretic gel or the blotting membrane and for screening a cDNA library. The entire process can be performed within 2 weeks and may be compatible with clinical laboratory practice. This procedure will be of use for the analysis of primary structure of idiotope, and for producing V-region peptides of functional MAbs and chimeric antibodies.

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