Antiphospholipid syndrome within systemic lupus erythematosus.
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Antibodies, Anticardiolipin↗
Biomedical subjects
D Alarcon-Segovia
Publications and source records attributed to D Alarcon-Segovia.
Presence of serum antibodies to coagulation protein C in patients with systemic lupus erythematosus is not associated with antigenic or functional protein C deficiencies.
Antibodies directed to immunopurified coagulation protein C (PC) were investigated in serum samples from 108 patients with systemic lupus erythematosus (SLE) and found in 12 of them. However, their presence was not associated with antigenic or functional deficiencies of PC, which were documented in 6 and 17 patients, respectively.
Antibodies↗
Erythermalgia, erythromelalgia, or both? Conditions neglected by rheumatologists.
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Aspirin↗
Interleukin-1 and interleukin-6 activities are increased in the cerebrospinal fluid of patients with CNS lupus erythematosus and correlate with local late T-cell activation markers.
We examined cerebrospinal fluid (CSF) samples from 12 patients with SLE and active central nervous system (CNS) involvement for their levels of the following cytokines: interleukin-1 (IL-1) by means of two different assays--the IL-1 responsive murine cell line LBRM 33-la5 and an ELISA for IL-1 alpha; IL-2 by means of the CTLL cell line responsive to it; and interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) both determined by a specific ELISA. We found that SLE CSF had significantly higher levels of IL-1 and IL-6 than did those obtained at surgery from eight controls without inflammatory neurologic disease. IL-2 and TNF were not detectable in any of the CSF samples. We also studied the status of activation in CSF T cells using monoclonal antibodies against early (anti-IL-2R (CD25) and anti-transferrin (CD71)), late (anti-T10) and very late (anti-VLA-1) activation antigens, and found increased percentages of T10-bearing (18 +/- 2 vs 3 +/- 0.7%) and VLA-1-bearing T cells (12 +/- 2 vs 0.7 +/- 0.2%) in SLE patients as compared to controls (both P < 0.01). Levels of IL-1 and IL-6 correlated with T10 and those of IL-1 correlated also with VLA-1. Markers of early T-cell activation did not differ in SLE and control CSF. Because of these findings we analysed the effect of recombinant IL-1, IL-6 or normal CSF on normal T cells and found that they did not induce the expression of activation markers.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Immunoglobulin heavy chain constant-region gene polymorphism in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is associated with immunoglobulin allotypes in several ethnic groups. In this study, we investigated the association of a Bst EII immunoglobulin heavy chain constant-region gene restriction fragment length polymorphism with SLE in patients from the US and Mexico. A 3-kb restriction fragment was observed with significantly decreased frequency in randomly selected Mexican SLE patients and in Mexican SLE patients in multiplex families. However, no such association was observed in SLE patients from the US. Thus, the absence of a 3.0-kb Bst EII restriction fragment from immunoglobulin heavy chain constant-region genes provides a marker for SLE in Mexican individuals.
Blotting, Southern↗
Defects of the retinal pigment epithelium in scleroderma.
We completed ocular examination, including retinal fluoroangiography, in 19 unselected patients with diffuse systemic sclerosis (scleroderma) and compared the findings with those made in 50 consecutive patients with systemic lupus erythematosus, 18 with primary Sjögren's syndrome, 20 with mixed connective tissue disease, and 20 healthy women. Five of 19 scleroderma patients had atrophy of the retinal pigment epithelium (26.3%) while none of the controls and only four of the 88 (4.5%) patients with other connective tissue diseases (P less than 0.01) had this anomaly. Atrophy of the pigmented epithelium of the retina may occur in scleroderma as a result of damage of the choroidal plexus.
Adult↗
T lymphocyte subsets, suppressor and contrasuppressor cell functions, and production of interleukin-2 in the peripheral blood of rheumatic fever patients and their apparently healthy siblings.
We studied CD4 and CD8 T cell subsets, suppressor cell function, production of IL-2, and immune contrasuppressor cell activity in 21 patients with rheumatic fever (RF), both at the time of their first acute episode and 3 months later (recovery phase). As controls we studied their healthy sibling nearest in age, as well as age- and sex-matched unrelated normal subjects. In the acute phase we found CD4+ T cells to be high, concanavalin A-induced suppression to be low, and production of IL-2 to be significantly decreased, as compared to the normal unrelated controls. The addition of contrasuppressor cells (VV+) to cell cocultures resulted in an increase in proliferation by mononuclear cells (MNC) in response to streptococcal M antigen but not to C carbohydrate antigen. In the recovery phase, CD4+ T cells became normal, CD8+ T cells rose above normal, and the suppressor cell functions (concanavalin-A-induced and spontaneously expanded), as well as the production of IL-2, fell further. Siblings were found to have increased CD8+ T cells and decreased production of IL-2, as compared to the unrelated controls. These findings indicate that important immunoregulatory disturbances occur during the acute phase of rheumatic fever, some of which persist, accentuate, or change during the recovery phase. The findings in siblings could be related either to streptococcal infection or to a familial immunoregulatory aberration.
Adolescent↗
Association between a T cell receptor restriction fragment length polymorphism and systemic lupus erythematosus.
The present study was designed to test the possibility that T cell receptor genes are associated/linked to those involved in systemic lupus erythematosus (SLE). Genomic DNA was isolated from 31 unrelated Caucasian SLE patients, 34 unrelated Caucasian normals, 5 multiplex American Caucasian SLE families, 9 multiplex Mexican SLE families, and 13 unrelated Mexican normals. The DNA was digested with Pst I, electrophoresed, and transferred to membranes by the Southern blot method. The blots were probed with a cDNA probe for the alpha chain of the T cell receptor. 13 polymorphic RFLP patterns were recognized. 1.3- and 3.0-kb band pairs were observed in 15 of 31 of American Caucasian patients and 4 of 34 American Caucasian controls (chi square, 8.81; P less than 0.002; relative risk, 7); there was no association of any RFLP pattern with Mexican SLE. The cDNA probe was cut with Rsa I, EcoR I, and Ava II into fragments corresponding to the V, J, C, and 3'UT regions. Only the fragment corresponding to the constant region reacted with the 1.3/3.0-kb band pair. These observations suggest that a genetic marker of the constant region of the alpha chain of the T cell receptor is associated with genes involved in SLE.
Autoantibodies↗
The frequency of complement receptor type 1 (CR1) gene polymorphisms in nine families with multiple cases of systemic lupus erythematosus.
Low levels of complement receptor type 1 (CR1) on the erythrocytes of patients with systemic lupus erythematosus (SLE) may be acquired or genetically determined. Nine families with multiple cases of SLE were studied using a CR1 probe and restriction fragment length polymorphism analysis, to address this question. The absence of a significant increase in the frequency of a 6.9-kb band (previously shown to be associated with low-level CR1 on erythrocytes) suggests that this genetic marker does not play a major role in determining SLE, either in these families or in SLE patients in general.
DNA Probes↗
A defect in immunoregulatory synovial fluid T cells in Behçet's syndrome.
Synovial fluid mononuclear cells from 5 patients with active Behçet's syndrome who were receiving no treatment were observed to have: decreased proportions of CD4+ and CD8+ cells, decreased proliferative responses of T cells in AMLR, poor capacity of non-T cells to stimulate in AMLR, decreased production of IL-2 upon PHA stimulation as compared both to their own peripheral blood mononuclear cells and to synovial fluid and peripheral blood mononuclear cells from 6 patients with RA and 6 patients with synovial effusions due to noninflammatory conditions. These findings provide further evidence of an immunoregulatory disturbance in Behçet's syndrome and indicate that synovial fluid, may be an important site where this derangement occurs in the active stage of the disease.
Adult↗
Effect of the new immunoregulator AS-101 on in vitro functions of mononuclear cells from patients with systemic lupus erythematosus.
We studied the in vitro production of interleukin-2 (IL-2), the expression of IL-2 receptors, the absorption of IL-2, and spontaneously expanded suppressor cell function by mononuclear cells from 15 patients with systemic lupus erythematosus (SLE) and 15 healthy control subjects. These functions were studied in the presence or absence of AS-101, a recently described organotellurium compound with immunoregulatory properties. AS-101 was found to be non-toxic to cells from both patient and control groups; it increased the production of IL-2, elevated the percentage of Tac-positive cells even among cells that had been pre-treated with pronase, and ameliorated the absorption of IL-2. It also enhanced the suppressor cell function in cells from SLE patients. Since these functions are known to be defective in vitro in cells of SLE patients, and since preliminary testing of AS-101 in humans indicates that it is a safe drug, this immunoregulatory compound holds promise for a novel and effective treatment of SLE.
Adjuvants, Immunologic↗
Mononuclear cell-fibroblast interactions in scleroderma.
We studied cell proliferation and collagen biosynthesis in cocultures of dermal fibroblasts with peripheral blood mononuclear cells (MNC) from scleroderma patients and from age-matched normal controls. Autologous one-way mixed MNC-fibroblast cultures revealed that fibroblasts do not stimulate MNC proliferation. Conversely, MNC stimulate autologous fibroblasts from scleroderma patients as well as from normal controls. This effect is increased in cells from scleroderma patients in which it seems to be mediated both by cell-to-cell interaction and through the production of soluble factors by MNC. In normal control cell systems we found no proliferative effect of supernatants of unstimulated cells or from those stimulated in autologous mixed-lymphocyte reactions. Coculture of fibroblasts with autologous MNC resulted in increased [14C]proline incorporation into both collagenic and noncollagenic proteins. This effect was mediated mostly by soluble factors that are released into the culture medium. Protein synthesis by MNC-fibroblast cocultures from scleroderma patients was significantly greater than protein synthesis by those from normal controls. Culture supernatants from unstimulated MNC or from autologous mixed-lymphocyte cultures caused a slight decrease in collagenic protein synthesis by cultured fibroblasts from scleroderma patients but not by those from normal controls. This effect of culture supernatants could be reproduced, and magnified, with purified IL-1 on cells from either patients or controls. Our findings indicate abnormal MNC-fibroblast interactions in scleroderma that could play an important role in the pathogenesis of fibrosis, the hallmark of this condition.
Adult↗
T-cell dysregulation in patients with hyperprolactinemia: effect of bromocriptine treatment.
We studied four patients with tumoral hyperprolactinemia and normal ovarian function before and after prolactine levels had become normal with treatment with bromocriptine (BrC), a dopamine agonist that inhibits prolactin release. Their proliferative responses to concanavalin A, pokeweed mitogen, and, to a lesser extent, phytohemagglutinin, their spontaneous and concanavalin A-induced suppression, and their production of interleukin 2 were found to be decreased and to correct partially or completely after bromocriptine treatment. The T-cell response to interleukin 2 was low in two patients in whom it increased after BrC treatment. These findings give insight on the immunomodulatory role of prolactin in vivo.
Adult↗
Stimulating and differentiation factors for human B lymphocytes in systemic lupus erythematosus.
T cells from 18 untreated SLE patients produced significantly more B cell growth factor (BCGF) than did those from normal subjects. Those from SLE patients with active disease produced significantly more than did those from patients with inactive disease. The response to BCGF of SAC-stimulated B lymphocytes from SLE patients was higher than that of B lymphocytes from normal individuals. Similarly preactivated B cells from five of seven SLE patients also proliferated upon the addition of interleukin 1 (IL-1) whereas those of normal subjects did not. Simultaneous addition of IL-1 and BCGF had a synergistic proliferative effect on B cells from two of seven SLE patients but not on any of the controls. Interleukin 2 (IL-2) had no proliferative effect in either SLE or normal B cells. Supernatant fractions from T cells of seven of 10 patients with active SLE and three of 10 with inactive SLE induced more IgG production by CESS cells than did those of normal subjects indicating a higher production of B cell differentiation factor by SLE T cells than by those of controls. Our findings may explain the reported preactivation and predifferentiation of peripheral blood B cells from SLE patients and give insight into the mechanisms leading to the production of autoantibodies in this disease.
Adolescent↗
The connective tissue diseases as disorders of immune regulation.
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Autoantibodies↗
Immunoregulatory circuits in the acquired immune deficiency syndrome and related complex. Production of and response to interleukins 1 and 2, NK function and its enhancement by interleukin-2 and kinetics of the autologous mixed lymphocyte reaction.
The production of the T cell lymphokine interleukin-2 (IL-2) was found to impaired in all of seven male patients with AIDS or homosexuals with persistent generalized lymphadenopathy (AIDS related complex, AIDS-RC) whom we studied. Conversely the T cell response to IL-2 was found unimpaired as was the production of the monocyte factor interleukin-1 (IL-1). The response of T cells to IL-1 was found markedly decreased in two of the four patients with AIDS and in two of the three patients with AIDS-RC. Five of six patients had flat curves in autologous mixed lymphocyte cultures with no significant proliferative response throughout 7 days. The exception was a Haitian heterosexual patient with AIDS. Natural killer cell function was decreased in three of four patients with AIDS and two of three patients with AIDS-RC but it augmented normally in the presence of IL-2 in four, including the two who had it normal basally. Responses to pokeweed mitogen were within normal limits in all seven patients despite decreased responses to concanavalin A and phytohaemagglutinin. These findings help pinpoint the defect in AIDS to the T4+ cell, and perhaps even to one of its subpopulations, and suggest a role for IL-2 in the treatment of AIDS.
Acquired Immunodeficiency Syndrome↗
Spontaneous production of, and defective response to, interleukin-1 by peripheral blood mononuclear cells from patients with scleroderma.
Interleukin-1 (IL-1) is a monocyte derived factor that participates in immune regulation and in the regulation of fibroblast proliferation and collagen deposition. It therefore, seems particularly pertinent to study in scleroderma, a disorder of immune regulation where increased collagen deposition is a hallmark. The production of IL-1 by lipopolysaccharide stimulated monocytes from 18 untreated scleroderma patients was akin to that of their normal matched controls. However, the unstimulated monocytes from six of the 18 scleroderma patients released IL-1 activity spontaneously into their supernatants. All six patients with spontaneous IL-1 release had less than 5 years disease duration. The response to IL-1 by T lymphocytes from patients with scleroderma was low as compared to those from controls. The presence of spontaneous IL-1 production with decreased response to IL-1 in scleroderma may indicate an in vivo pre-activation of monocytes to produce this factor that might have a bearing in the pathogenesis of collagen deposition in scleroderma.
Adult↗
Antilymphocytic antibodies in mixed connective tissue disease.
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Antilymphocyte Serum↗