[Autoimmune hepatitis and CREST syndrome]. / Hépatite auto-immune associée au syndrome de CREST.

We report the case of an autoimmune hepatitis in a 59-year old woman who was referred for a progressive jaundice. The patient had an history of CREST syndrome. The particularity of this case report is the rare association between these two autoimmune diseases.

A reference standard for plasma proteins is required for nutritional assessment of adult burn patients.

Plasma levels of visceral proteins (VP) are commonly used for evaluation of nutritional status. Low values observed in burn patients are caused by several factors including microvascular hyper-permeability and inflammatory processes. The aim of the study was to define a range of standard values specific to burn patients. Retrospective review: from days post-burn 12 to 43, four VP and three acute phase reactants (APR) were measured twice a week, in the plasma of 107 burn patients. From these data, standard' values were determined in respect with burn surface area (BSA) and post-burn time. The results were that the VP increase and APR decrease linearly during the study. Correlation between plasma proteins and BSA or post-burn day, change from protein to protein. Albumin and transferrin are less sensitive than prealbumin and especially retinol binding protein to variations of APR, but transferrin lacks of specificity. The conclusion of the study was that plasma levels of VP have to be compared to reference standard values. When levels lower than theoretical values are observed, simultaneous APR values (especially C reactive protein) have to be compared to their own reference standard, in order to separate nutritional from inflammatory effects.

Ankylosing spondylitis with primary Sjögren's syndrome: the first two case-reports.

Sjögren's syndrome and ankylosing spondylitis can occur either alone or in conjunction with other disorders. We report on two patients who met criteria for both primary Sjögren's syndrome and ankylosing spondylitis. Class I and II histocompatibility phenotypes were strikingly similar in the two patients and are in favor of a chance association.

Rheumatic manifestations due to human parvovirus B19. A report of four cases.

Human parvovirus B19 has been incriminated in the genesis of hematologic, dermatologic, neurologic, and rheumatic disorders. We report four cases in which inflammatory rheumatic manifestations developed during the course of human parvovirus B19 infection documented by the presence of IgM and IgG antibodies. There was one case each of monoarthritis, oligoarthritis, polyarthritis, and enthesitis. Three patients had a favorable outcome under nonsteroidal antiinflammatory drug therapy, and one developed reflex sympathetic dystrophy syndrome. In patients with inflammatory rheumatic manifestations that do not fit any specific diagnosis, a careful family history can provide evidence suggesting human parvovirus B19 infection, which should be confirmed by tests for IgM and IgG antibodies.

Chronic eosinophilic pneumonia followed by Churg-Strauss syndrome.

Chronic eosinophilic pneumonia and Churg-Strauss syndrome are two uncommon conditions of unknown etiology that share similar pulmonary manifestations. Whereas chronic eosinophilic pneumonia mainly targets the lung, Churg-Strauss syndrome is a systemic diseases. We report three patients who developed Churg-Strauss syndrome about eight years after being diagnosed with chronic eosinophilic pneumonia. Hypereosinophilia and high IgE levels were present in both conditions. Elevation of IgA levels was consistently demonstrated at the time of the diagnosis of Churg-Strauss syndrome. IgA elevation may be useful as a marker for progression of chronic eosinophilic pneumonia to Churg-Strauss syndrome.

Chronic interstitial cystitis occurring during the shift between rheumatoid arthritis and lupus.

This case reports documents the progressive development of chronic interstitial cystitis during the overlapping process from rheumatoid arthritis to lupus. Concomitantly high titer antinuclear antibody with an anti-68 KD RNP pattern and other biological markers of lupus were observed in the blood. The symptoms dramatically improved under methotrexate therapy. The pathogenic mechanism is discussed.

Neurological manifestations of systemic lupus erythematosus: role of antiphospholipid antibodies.

Antiphospholipid antibodies (APL) are associated with venous and arterial thrombosis in SLE patients. Various thrombotic and non-thrombotic neurological manifestations have been reported in SLE but whether or not they are related to the presence of APL antibodies remains uncertain. To assess the possible association between neurological involvement in SLE and APL antibodies, IgG anticardiolipin antibodies (IgG ACL) were looked for using an ELISA technique in 92 consecutive SLE patients seen over a one-year period. Other APL determinations included VDRL and lupus anticoagulant (LAC) testing using APTT and the diluted thromboplastin time. Twenty-four SLE patients presented with neurological manifestations (40 episodes): 15/24 (62.5%) were found positive for APL antibodies (11 VDRL, 8 LAC, 7 ACL antibodies) versus 22/68 patients (32%) without neurological symptoms (p < 0.01). APL antibodies antedated neurological symptoms in 13/16 cases. Neurological manifestations were subsequently divided into 3 groups: thrombotic (n = 14), psychosis and convulsions (n = 15), miscellaneous (n = 10). No correlation was found between APL antibodies and any of the 3 subgroups. Among patients with neurological SLE, APL antibodies were present in two with valvular heart disease, as well as in seven with a history of either deep vein thrombosis, livedo reticularis or miscarriage. Among 7 patients with thrombocytopenia and neurological symptoms, 6 had APL antibodies. These data suggest that APL syndrome is associated with neuro-ophthalmological manifestations of SLE regardless of whether or not the mechanism of neurological involvement is thrombotic. SLE patients with APL antibodies may be at risk for future neurological manifestations. However, it is still questionable that APL positivity has definite therapeutic consequences.

Elbow synovitis related to an intraarticular osteoid osteoma of the humerus, with immunologic and histochemical studies.

An 18-year-old boy presented with elbow synovitis. Investigations disclosed an osteoid osteoma of the coronoid fossa confirmed by histology. The synovium appeared hypertrophic with histologic patterns resembling those seen in synovitis in rheumatoid arthritis. Immunohistochemistry showed lymphoid follicles composed of B and T cells. T lymphocytes were mainly of the CD4 phenotype, showing soluble interleukin 2 receptor (IL-2r) in places but were poorly positive for DR antigen. C3, C4, B factor and CH50 activity were decreased and interleukin 1 and soluble IL-2r were increased in synovial fluid. They were normal in peripheral blood except for a slight decrease in C4. These data suggest a local immunologic activation induced by osteoid osteoma, the mechanism of which remains hypothetic. Immunomodulating mediator diffusion from osteoid osteoma itself or as a secondary response to tumoral antigen release could be advocated. Whether such phenomena are specific to the epiphyseal location of osteoid osteoma needs clarification.

Multiple sclerosis: cell-mediated immunity to human brain gangliosides.

Cell-mediated immunity (CMI) to myelin components has been implicated in Multiple Sclerosis (MS) pathogenesis: two targets were suggested, Myelin Basic Protein with controversial results and, more recently, gangliosides. In order to investigate their possible involvement, we have performed Leukocyte Migration inhibition (LMI) tests in the presence of human brain gangliosides. Thirty nine MS patients (twenty four being "definite", according to McDonald and Halliday's classification), twenty nine patients with Other Neurological Diseases (OND), thirty six patients with Inflammatory diseases (ID) and forty healthy controls were tested. MS patients were divided into two groups, depending on the clinical stage of the disease. The mean migration inhibition percentage of the MS-attack group was found to be significantly different from the four others (p less than 0.01) (24.4 +/- 16.2 versus 10.9 +/- 8.5 in MS without attack, 4.4 +/- 12.9 in OND, 3.9 +/- 13.9 in ID and 11.1 +/- 12.1 in healthy subjects). LMI to gangliosides is therefore significantly increased during the attack stage in MS. These results support the notion of a Delayed Type Hypersensitivity to these glycolipids during the active stage of the disease.

Regulation of experimental autoimmune encephalomyelitis. Specificity of the 'recovery-associated' suppressor cells.

We previously reported the presence of suppressor cells in Lewis rats at the very time of spontaneous recovery from experimental autoimmune encephalomyelitis. As these 'recovery-associated' suppressor cells might be implicated in the self-cure process, we investigated their specificity on the in vitro lymphoproliferative responses of a T cell line specific for myelin basic protein (MBP). We report now that these suppressor cells found in the thymus are specific for MBP, and not for T cell receptors, contrasting with the 'post-recovery' suppressor cell specificity reported by others. Furthermore, they do not recognize the encephalitogenic peptide 71-84, suggesting that their specificity involves an epitope outside (or partially out of) the encephalitogenic sequence.

[Experimental autoimmune encephalomyelitis: immunoregulation and genetic control]. / Encéphalomyélite autoimmune expérimentale (EAE): immunorégulation et contrôle génétique.

EAE is a good model of autoimmune diseases and an approximate one of MS, particularly in its chronic recurrent and demyelinating forms. The antigenic target of EAE has recently been better defined: in different species, as well as within a given one, the encephalitogenic determinant, target of T effector cells, is located in different parts of the basic protein of myelin. The recognition of the relevant epitope is influenced by the genotype of the antigen presenting cells. By analogy, in MS, one can expect to find various target-antigens for the immune (autoimmune?) reactions that occur in the Central Nervous System of different patients, may be in correlation with HLA phenotype. The study of immunoregulatory processes in EAE suggests a possible role for suppressor cells and for variations in the capacity of interleukin-2 production. Similarly, in MS, variations in suppressor cell activities have been found in acute attacks. Finally, the possibility of "vaccinating" against EAE with attenuated encephalitogenic line cells, opens new interesting perspectives in the therapy of MS.

An OKT4+ T-cell population in Sézary syndrome: attempts to elucidate its lack of proliferative capacity and its suppressive effect.

We have previously reported a case of Sézary Syndrome (SS), in which an OKT4+ T-cell population exhibited a defective response to non-specific mitogens, and an ability to suppress lectin-induced T-cell proliferation and pokeweed mitogen (PWM)-induced B-cell differentiation of normal donor peripheral blood mononuclear cells (PBMC). We report now that resting Sézary cells (SC) were essentially negative for activation antigens (Ag) detected by monoclonal antibodies (MoAb) B1.49.9, anti-Tac, OKT9, OKT10, and OKIa1. After phytohaemagglutin (PHA) stimulation, all these Ag were expressed with the notable exception of OKT10. Further investigations of SC functions indicated that no interleukin 2 (IL-2) biological activity was detected in culture supernatants of SC constimulated with PHA and phorbol myristate acetate (PMA). Interestingly, such stimulated SC exhibited a marked capacity to absorb exogenous IL-2 while remaining unable to proliferate. These data suggest that patient's unresponsiveness to PHA may be unrelated to IL-2 as an extracellular growth signal, but may instead be due to a failure in a later cellular activation event, subsequent to the binding of IL-2 to its receptors. Lack of T10 Ag expression may be involved as a cause or a consequence. Kinetic study of suppression of PHA-induced T-cell proliferation of normal PBMC revealed that inhibition occurred during the first 24 h; moreover we showed that it was not due to limitation of available IL-2 since it persisted in excess of IL-2; remarkably the growth of an IL-2-dependent murine cell line was unaffected by the presence of SC. Further, inhibition was also observed on IL-2-independent calcium ionophore A 23187-induced T-cell proliferation of normal PBMC. Taken together, the data suggest that the target of suppressor activity is probably an important obligatory intracellular event controlling DNA replication, which is common to both IL-2-dependent and IL-2-independent T-cell activation processes. Human T-cell leukaemia/lymphoma virus I (HTLV-I) related p.19 and p.24 Ag were absent on fresh and 30-day cultured SC, suggesting the absence of HTLV-I infection, although not ruling out a proviral integration in the SC DNA.

Detection of HTLV-I (human T-cell lymphotropic virus, type I) proviral DNA in leukemic cells from a French patient with Sezary syndrome.

Human T-lymphotropic type I (HTLV-I) proviral sequences were detected in leukemic cells of a patient living in Marseilles (south of France) and suffering from Sezary syndrome. He did not have any travel history outside France and did not receive blood transfusion or hepatitis B vaccination. This case of HTLV-I positive Sezary syndrome is the first one described outside the known endemic regions for HTLV-I. Moreover, this patient was found to be negative for viral antibodies. This observation should therefore stimulate new and thorough analysis of the association of this human retrovirus with leukemia and lymphoma in the Mediterranean region, both by seroepidemiological and molecular biology techniques.

An OKT4+ T-cell population with suppressor activity in Sézary syndrome.

This report describes a case of Sézary syndrome with the surface marker phenotype of a mature distinct T-cell subset OKT3+, OKT4+, OKT8-, OKT17+, OKIal-(+). Functional studies indicated that the patient's peripheral blood cells showed a very low proliferative response to non-specific mitogens (phytohaemagglutinin, concanavalin A, pokeweed mitogen) and failed to differentiate into plasma cells in a pokeweed mitogen--immunoglobulin-synthesis-driven system. In coculture with normal cells the leukaemic cells were able to suppress lectin-induced T-cell proliferation and B-cell differentiation in a dose-dependent manner. Suppressor function was not radiosensitive and did not require the presence of the OKT8+ subset for expression. These Sézary cells thus represent a suppressive T-cell subset within the OKT4+ population. This subset may well correspond to the recently described OKT4+, OKT17+ normal suppressor cells. These findings would therefore illustrate a pathological and possibly clonal expansion of a normal OKT4+ suppressor T-cell subset.