Immunological evidence of chlamydial infection in Reiter's syndrome.
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Biomedical subjects
Publications and source records attributed to A Kahan.
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NZB mice treated with interferon from birth and for over a year, display early some characteristics of the autoimmune disease. In these animals, mortality is clearly higher than in controls. Their death occurs 3 to 6 months before that of mice injected with a "mock" preparation.
Experimental model of human chronic inflammatory arthritis, adjuvant arthritis may be induced only in several strains of inbred Rats: it is well developed in LEW and practically absent in WAG. After adjuvant injection, the PHA-stimulable lymphocytes subpopulation quite disappears from the blood, if polyarthritis is well developed. These cells are probably capted in the tissues implicated in immunological conflict. On the contrary, the ConA-stimulable subpopulation is enhanced in both strains after adjuvant injection, earlier and more intense in WAG than in LEW and that phenomenon is probably linked to a stimulation of suppressor T lymphocytes. Treatment with prednisone or gamma rays inhibits partially and delays the appearance of arthritis in LEW, acting essentially on ConA-stimulable subpopulation.
Cyclophosphamide is given intravenously in the high dose of 12 mg/kg/day during 2 months from the beginning of immunological systemic connective tissue disease in rabbits, according to the modified Glynn's model. The effects of this alkylating drug are studied after the termination of treatment. At short term (15 days), cyclophosphamide depresses the inflammation of synovia in stimulated and non-stimulated joints, the humoral and cellular immunities, but the drug does not modify the other systemic lesions. At long term (between 1 and 6 months), these effects of cyclophosphamide disappear completely.
In patients with ankylosing spondylitis (AS) the plasma level of beta2-microglobulin (beta2m) is signficantly higher (1.95 +/- 0.48 mg/l) than in osteoarthritis (1.48 +/- 0.47 mg/l). In Reiter's syndrome the level of beta2m is also higher than in controls, but the paucity of results do not allow definite conclusions. The plasma level of beta2m in AS and in Reiter's syndrome is not related to the presence of HLA B 27 antigen, neither to other biological parameters as sedimentaton rate, blood cell counts, electrophoresis of plasma proteins. In rheumatoid arthritis the plasma level of beta2m is 2,67 +/- 0.84 mg/l, significantly higher than in osteoarthritis or in AS even without any association with Sjögren's syndrome. In synovial fluid, the beta2m level is closely related to the degree of inflammation, suggesting a local production of this substance.
Articular inflammatory involvement may be the first sign of gluocecerebrosidase deficiency (Gaucher's disease). Electron microscope study shows specific synovial storage lesions which explain arthritic manifestations. Furthermore presence of mitochondrial microcrystals, (apatite?), suggest microcrystal pathogenesis of Gaucher's arthritis.
Optical and electron microscopic studies of the articular fluid in multiple calcification disease reveals the existence of rounded intra- and extracellular crystalline formations. These crystalline formations of calcium and phosphorus are made up of accumulations of tiny crystals shaped like fine needles 200 nm X 15-20 nm and are highly suggestive of hydroxyapatite. Crystals injected into the plantar pads of rats or the knees of rabbits induce an acute inflammatory reaction maximal at 5 hours and recovering in 24 72 hours. Hydroxyapatite crystals are swiftly dissolved in serum and more rapidly still when cells are present. Their dissolution releases calcium into the surrounding area. HLA typing of patients with multiple tendinous calcification (28 cases) or single tendinous calcification (10 cases) shows an increased frequency of HLA A2 and BW 35 in comparison with controls.
Attempts were made to isolate a virus from systemic lupus erythematosus patients, using lymphocyte cultures prepared from peripheral blood. Both cocultivation with VERO cells and fusion experiments in which lysolecithin and Concanavalin A were employed as fusing agents failed to reveal any presence of virus. Con A proved to be useful for heterokaryon formation in primate cells, fusion levels varying from 14-21% as shown by autoradiography.
The lymphoblastic response (LTT) to non-specific mitogens (PHA, PWM and ConA) of peripheral lymphocytes was investigated at days 0, 7, 14, 21 and 28 after adjuvant injection in four strains of inbred rats: Wistar (WAG), Long Evans (LE), Lewis (LEW) and Brown Norway (BN). LTT was assessed by using 18 hours H3 TdR incorporation in 5 days cultures of whole blood (micromethod). The statistical treatment of data, using principal components multifactorial analysis and analysis of variance showed a striking difference between strains. In control animals the responses to PHA and PWM were correlated and were higher in LE and WAG than in LEW and BN (BN=LEW less than LE=WAG). The response to ConA was independent of that to the other mitogens. It was generally low, but significantly higher in LEW and BN than in WAG and LE. In adjuvant-injected animals the responses to PHA and PWM were still correlated, but modified compared to control: in LE and LEW, but not in WAG and BN, a marked decrease of the response was found, reaching a minimum value within days 7 and 14. In the same time the response to ConA increased in the four strains, later in LE than in the others. However the intensity of the ConA response varied from one strain to another: it was constantly low in LE and WAG compared to LEW and BN. So the most striking modification of LTT were observed in LE and LEW, which both developed the most severe arthritis. However these different behaviours after adjuvant injection were not explained by the initial level of LTT to the different mitogens. These data suggest that the development of intense arthritis is associated with the proliferation and the release into the blood stream of a lymphocyte subpopulation, which exhibits a low response to PHA and PWM and a high response to ConA. These LTT modifications are not paralleled by quantitative variations of B-cells assessed by surface Ig immunofluorescent staining and EAC rosetting.
The antigenicity of aqueous extracts of osteoarthritic and rheumatoid synoviale was studied in patients with rheumatoid arthritis, other diseases and in normal controls by the mean of leucocyte migration test, lymphoblastic transformation test and cutaneous reactions. In 59% cases of rheumatoid arthritis an inhibition of the migration of leucocytes was found but there was no relation between this test and the clinical state, the evolution, rheumatoid serology and other laboratory parameters. In some cases of rheumatoid arthritis an inhibition of the migration of leucocytes was observed also with a pericardial and hepatic extract. In normal controls the leucocyte migration test is always negative, but it is positive in 37% of cases of various inflammatory and neoplastic diseases and the difference is not significant considering the percentage of positivity of the test in rheumatoid arthritis. The lymphoblastic transformation test and the cutaneous reactions were always negative in rheumatoid arthritis and in controls. Thus, the leucocyte migration test using a synovial extract as an antigen does not bring evidence in favour of an auto-immune conflict in rheumatoid arthritis.
A knee joint arthritis is induced in rabbits previously immunized by an intradermal injection of emulsified egg albumin (E.A.) a complete adjuvant, then by an intra-articular injection of E.A. alone. Histologically, the synovium shows at first an Arthus phenomenon and later an immune cellular reaction. Several immunological parameters are studied in these rabbits. Cyclophosphamide (CY), injected intravenously, in a high dose, during a short period from the day of the first immunization, inhibits in the same time the arthritis index, E.A. skin test, humoral and synovial anti-E.A. antibodies and lymphocyte response to P.H.A. Cy, injected I.V., in a low dose, for a long period from the day of the intra-articular immunization, decreases only the arthritis index, but does not modify the various immune reactions to E.A. These results suggest that, according to the timing and the dose, CY inhibits synovial inflammation either by a strict anti-inflammatory action, or by an immunosuppressive effect on the initial phase of the immune reaction inducing subsequently a synovial inflammation.
The number of large circulating hyperbasophilic mononuclear cells - referred to as hyperbasophilic immunoblasts (HBI)- is often increased in collagen disease and rheumatoid arthritis (RA) and grossly reflects the degree of disease activity. In contrast, in psoriatic arthropathy the percentage of (HBI) is within the normal range. HBI are mainly involved in immune reactions and may provide a valuable routine test for the assessment of the latter in disease states and for the predicition of relapse in chronic collagen diseases. Immunofluorescent techniques applied to samples from active autoimmune diseases have shown that a number of HBI are Ig-producing B-blasts. Moreover, in a few cases these intracytoplasmic immunoglobulins exhibited a rheumatoid factor-like activity, a finding which promises to yield additional information on the immunopathogenesis of RA.
The authors studied the tissue groups in a first series of patients with properly diagnosed rheumatic disorders. They found HL-A W27 antigen in 84 percent of 50 cases of primitive ankylosing spondylarthritis in adults, in 33 percent of the 50 cases of Fiessinger-Leroy-Reiter syndrome, in 20 percent of the 40 cases of psoriatic polyarthritis (50 percent of the 12 cases with radiological sacroiliac involvement) and in 66 percent of the 6 cases of spondylarthritis associated with haemorrhagic rectocolitis. In a second series of 45 patients with unclassifiable inflammatory rheumatism, only the W27 antigen tested for and it was found in 33 percent of the patients. On the basis of these observations, which were compared with those in other publications, the authors confirm the absence of a clear correlation between the pathological picture and the presence of the W27 antigen. They discuss the significance of the association between the W27 antigen and the disease, and underline the diagnostic and sometimes the prognostic value of the W27 test in rheumatology.
Knee joint arthritis is induced among rabbits previously immunized by intradermal injection with egg albumin (EA) emulsified in adjuvant containing either M. tuberculosis or M. butyricum, then by intra-articular injection with EA. Arthritis evolution involves two phases, an early one during the first 2 months and a late one from 3 months to 1 year. During the early phase, arthritis intensities are similar no matter which Mycobacterium is used. However, during the late phase, only rabbits immunized with M. tuberculosis develop self-perpetuating arthritis. Among more than 50% of arthritic rabbits, immunological lesions of aortic artery and cardiac valvules are found. Among the rabbits immunized with M. tuberculosis, the humoral anti-EA antibody level remains constant during the whole arthritis evolution; but, among the rabbits immunized with M. butyricum, the arthritis intensity decreases from 3 months of evolution. The correlation between arthritis index (AI) and humoral antibody level is only significant among the rabbits with early arthritis. The intradermally immunized rabbits show a positive skin test with EA and tuberculin. The more intense the cutaneous reactions, the greater the chances of developing self-perpetuating arthritis after the EA intra-articular injection. The fluorescent anit-EA antibodies in the synovia and spleen are found only among the early arthritis. After 2 months of evolution, fluorescent antibodies disappear whatever the immunization may be. Among the immunized rabbits, it is probable that antigenic EA does not persist in the synovia. Indeed, the autologous inflamed synovia transplantation, from the donor-challenged knee joint, does not develop an inflammatory reaction in the non-challenged knee joint. The fluorescent immunoglobulins IgG and IgM in the synovium of arthritic rabbits are found with the same percentages as fluorescent anti-EA antibodies. The lymphocyte response to EA, PHA and PWM are positive whatever the immunization and arthritis evolution may be. There is no correlation between AIs and lymphocyte responses to specific and nonspecific mitogens. It is probable that self-perpetuation depends closely on M. tuberculosis whose adjuvant power is much superior than M. butyricum and not on antigenic EA whose essential role would be to trigger the inflammatory process.
Two new cases of association between a thymoma and a lupus illness are reported. The first was a women aged 42 years in whom were discovered simultaneously systemic lupus erythematosus (SLE) and a slowly invading thymoma, the histology of which was characterized by the predominance of epithelial cells; excision of this tumour did not appear to affect the evolution of the SLE. In the second case, a patient aged 60 years suffered from SLE ten months after the removal of a benign thymoma in which there was a predominance of lymphocytes. The SLE in this patient was easily controlled for more than a year by small doses of corticoids, but resulted in death after three years when anuria was associated with meningeal signs after the cessation of corticotherapy. The comparision of the data from these cases with those from eleven other cases in which there was association between a thymoma and SLE, brought to light several interesting facts. It is rare that SLE clearly precedes the discovery of the thymoma; it usually occurs afterwards or the two are discovered almost simultaneously. Collagenosis is of importance only when it coexists with a thymoma : starting later much more often than is usual in cases of SLE. The tumours were, in all but two cases, benign thymomas of different histological types, and their removal did not apparently influence the evolution of the SLE.
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