[Retroperitoneal fibrosis and arthritis--a manifestation of the same illness]. / Retroperitonealfibrose und Arthritis--Manifestation derselben Erkrankung.

Retroperitoneal fibrosis is a disorder in which the retroperitoneal fat is the site of a subacute and chronic inflammatory reaction and is subsequently replaced by dense fibrotic tissue. Rheumatoid nodules are chronic granulomata occurring at sites of pressure and movement, both near the body surface and internally. A 55-year-old sales-manager was admitted to radiation synovectomy after a 5 year history of excessive right and left knee effusions. There were no other clinical or laboratory abnormalities. The patient did not respond to either radioisotope synoviorthesis using radioactive Yttrium (90 Y), or to open synovectomy and prostetic surgery of the right knee. One year later, surgery of left ureter was necessary. Histological findings revealed the diagnosis of Ormond's disease. Comparative histological studies of synovial membrane of knee and retroperitoneal tissues showed local necrosis, fibrin deposition, lining cell proliferation, and infiltration by lymphocytes. Diagnosis of arthritis complicated by retroperitoneal rheumatoid nodules and retroperitoneal fibrosis was made. Serum rheumatoid factor has been negative. For the last 3 years, the patient has been on successful therapy with azathioprine. Rheumatoid nodules of the retroperitoneum have vanished completely and frequency of knee effusions decreased.

[Anti-Jo-1 antibodies: specific autoantibodies for polymyositis with interstitial pulmonary fibrosis. 2 case reports]. / Anti-Jo-1-Antikörper: Spezifische Autoantikörper für Polymyositis mit interstitieller Lungenfibrose. 2 Fallvorstellungen.

Anti-Jo-1 antibodies are rare autoantibodies, which bind and inhibit the activity of histidyl-tRNA-synthetase. They are predominantly found in a genetically and clinically distinct subset of myositis patients, presenting with interstitial alveolitis. We describe the case of a 22-year-old woman with Jo-1-syndrome with typical features of myositis, pulmonary fibrosis, nonerosive symmetric polyarthritis, Gottron's papules at the metacarpophalangeal joints and classic heliotrope discoloration of the periorbital area with edema. The patient did not respond to chloroquine, azathioprine, intravenous immunoglobulins or cyclophosphamide. Remission was finally achieved with oral methotrexate plus corticosteroids. The second case describes a 34-year-old man with myositis, who rapidly developed respiratory insufficiency after suffering from joint pain and stiffness for about 10 weeks. He responded well to cyclophosphamide pulse therapy and high-dose corticosteroids. The second case demonstrates that control of the interstitial alveolitis is most important for long-term outcome. Therefore, immunosuppressive drugs should be used along with corticosteroids as early as possible.

Improved classification of proteinuria by semiautomated ultrathin SDS polyacrylamide gel electrophoresis.

The quantitative and qualitative analysis of proteinuria by electrophoretic means proved to be a potent diagnostic tool for differentiation of functional renal impairment. The purpose of this study was to compare the macro scale SDS-PAGE technique, which has been used for the last two decades, with semiautomated electrophoresis using an ultrathin SDS-PAA gel with silver staining (Phast system). The new system proved to be quick and easy to handle. Separation of proteins in the range of 70-320 kD were of comparable quality to the macro scale system (unselective and selective glomerular proteinurias with 68 to 150 and 68 to 350 kD components, respectively, as well as total serum proteins), but there was considerable improvement regarding the quality and visibility of protein bands in the range of 11-70 kD. This improvement led to a new classification of micromolecular protein bands into three groups: the smallest microproteins (11-22 kD), the larger microproteins (23-40 kD) and the largest microproteins (41-68 kD). Thereby it was possible to obtain an improved definition of electrophoretic patterns of urinary proteins, which is described in detail.

[Fractional clearance of beta-2-microglobulin in the diagnostic and prognostic assessment of kidney diseases]. / Fraktionelle Clearance des beta-2-Mikroglobulins in der Diagnose und Prognosestellung bei Nierenkrankheiten.

The micromolecular proteinuria (67-11 Kd), originating from tubulo-interstitial disorders, might be determined by SDS- or gradient-PAGE or by individual marker proteins. The latter procedure in addition to PAGE is necessary in case of heavy proteinurias. The tubular resorptive capacity for microproteins, analysed by fractional beta-2-M-clearances, decreases with deteriorating GFR. Values for FrCl beta 2M above the expected level were associated with tubulo-interstitial, but also with diabetic and rapidly progressing glomerular nephropathies. In the latter group these findings might be of prognostic importance. In contrast, the U-beta-2-M-determination in long term observation of kidney transplants had no diagnostic nor prognostic value.

T cell cytotoxicity to Epstein-Barr virus infected B cells: comparison of patients with rheumatoid arthritis and their HLA identical siblings.

Specific T cell cytotoxicity to Epstein-Barr virus (EBV) infected B cells is reported to be abnormal in rheumatoid arthritis (RA). The regression phenomenon was used to determine whether the immunoregulatory defect in RA is restricted to T cells, B cells, or HLA type. Peripheral blood T and B cells from patients with RA and their HLA identical healthy siblings were mixed in varying ratios with and without EBV, and thymidine incorporation was measured on days 7, 14, and 21. The results suggest that the T cell abnormality is related to disease activity and that an inherent defect exists in the rheumatoid B cell which is independent of disease activity.

Parvovirus associated antigen in the synovial membrane of patients with rheumatoid arthritis.

Homogenates of synovium from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were centrifuged on caesium chloride density gradients to obtain isolates of a density similar to that of parvoviruses. Six of 11 RA isolates and none of six OA isolates reacted with an antiserum raised against a rheumatoid associated, parvovirus-like agent (RA-1 virus). An anti-B19 parvovirus antiserum did not react with any of the isolates tested. Electron microscopy of negatively stained preparations of the isolates showed that small particles of diameter 10 nm were abundant in most of the RA isolates (11/13) but absent from all OA isolates. Such particles, whose identification is unknown, were also present in RA-1 positive lysates prepared from cultured RA synovial cells. These results suggest that the RA-1 virus can be directly identified in RA synovial tissue and that the virus appears to be unrelated to the human B19 parvovirus.

The effects of adherent cells on measurement of the hyper-responsiveness of rheumatoid B lymphocytes to Epstein-Barr virus.

Rheumatoid peripheral blood mononuclear cells show an increased responsiveness to superinfection with Epstein-Barr virus (EBV). We have investigated the role of adherent cells in this hyperresponsiveness using two different methods of adherent cell depletion. Depletion of adherent cells from both rheumatoid and normal mononuclear cells, using either dextran bead columns or plastic petri dishes, produced inconsistent changes in the response of autologous non-adherent cells to EBV. The addition of supernatants of cultured rheumatoid adherent cells also produced an inconsistent change in response although normal adherent cell supernatants increased the responsiveness of autologous non-adherent cells to EBV. The inconsistencies observed are discussed with respect to adherent cell subpopulations present in rheumatoid and normal peripheral blood mononuclear cell preparations when using recognized methods of adherent cell depletion.

[In vitro and in vivo studies with interleukin 2 (IL-2) and various immunostimulants in a patient with AIDS]. / In-vitro- und In-vivo-Studien mit Interleukin-2 (IL-2) und verschiedenen Immunstimulanzien bei einer Patientin mit AIDS.

We report on a lethal course of an acquired immunodeficiency syndrome (AIDS) in a young female patient. She had spent her vacancies six years before diagnosis in Haiti, where a sexual intercourse with a Haitian man had occurred. Leading clinical symptoms consisted of recurrent Herpes simplex infections of the genital and perianal region as well as unexplained high temperatures. There were some typical laboratory and immunologic features of this disease with leukopenia, hypergammaglobulinemia, cutaneous anergy, a reduction of peripheral T-lymphocytes (OKT 3) and an almost complete loss of OKT 4 (helper cells) positive lymphocytes. The mitogenic response upon stimulation with allogeneic cells (MLC) or with the mitogens PHA, Con A and PWM was significantly reduced. There was no measurable interleukin-2 (IL-2) secretion of peripheral blood lymphocytes. Several immunostimulators (thymopentin, inosiplex, bestatin) were tested in lymphocyte proliferation assays in vitro. The mitogenic response could not be enhanced by neither of these substances. A clinical trial with Delimmun (inosiplex) for 14 days did not show any clinical or immunologic improvement in this patient. The intravenous application of high dose immunoglobulin G was without any observable effect. The proliferation inducing capacity of a highly purified IL-2 preparation on the AIDS cells in vitro led us to a clinical trial with this substance. We applied 100 Bödeker units of IL-2 per kg body weight and day subcutaneously for 16 days. A therapeutical effect, however, could not be observed. Cell marker analyses did not show significant changes in lymphocyte subpopulation composition under IL-2 therapy. There was an increase in the spontaneous cell proliferation 14 days after start of IL-2 therapy. The PHA- and IL-2 response of the AIDS cells, however, was unchanged. It cannot be excluded that an administration of IL-2 in earlier stages of AIDS may have beneficial effects.

Increased numbers of active B cells in the circulation of patients with rheumatoid arthritis.

Increased numbers of cells secreting immunoglobulins of class G, M and A have been demonstrated in the peripheral blood of patients with active rheumatoid arthritis using the reverse haemolytic plaque assay. Lower numbers of secreting cells were detected in rheumatoid patients in spontaneous remission. Culture of the peripheral blood mononuclear cells was associated with a fall in the number of immunoglobulin secreting cells. Values for rheumatoid and normal cells did no differ significantly after 3 days of culture. The presence of an activating factor in th rheumatoid patients is postulated.

Increased responsiveness of rheumatoid B lymphocytes to stimulation by Epstein-Barr virus.

Blood lymphocytes from rheumatoid patients and normal subjects were examined for responsiveness in culture to Epstein-Barr virus (EBV) infection by outgrowth assay and 3HTdR uptake. With both unseparated and B-cell-enriched lymphocytes the frequency and rate of outgrowth to form permanent cell lines were significantly higher for rheumatoid than for normal cells. In B-enriched rheumatoid preparations the proportion of responsive cells was also greater, and DNA synthesis was induced by a lower infecting dose of EBV in rheumatoid than in normal cells. The percentage of autologous T cells needed to ensure regression of B-cell proliferation in EBV-infected cultures was considerably higher with rheumatoid than with normal cells. These findings suggest that in rheumatoid arthritis the abnormal lymphocyte responsiveness to EBV has two components, a T-cell immunoregulatory defect, and a separate increased responsiveness of B cells to EBV.

In vitro induction of anti-intermediate filament antibody in lymphocyte cultures by Epstein-Barr virus.

Serum antibodies reactive with intermediate filaments of the cytoskeleton (anti-IF antibodies) are often present in infectious mononucleosis, some other viral diseases, and rheumatoid arthritis. The mechanism of their production is not known, but it is possible that the formation of this and other autoantibodies result from polyclonal activation of B-cells. Peripheral blood mononuclear cells from subjects with or without serum anti-IF antibody were therefore cultured in the presence or absence of Epstein-Barr virus (EBV). IgM anti-IF antibody was produced in both unfractionated and T-cell-depleted cultures, but not in the supernatants of the same cells cultured without added EBV.