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D Alarcon-Segovia

Publications and source records attributed to D Alarcon-Segovia.

At least 19 recordsLinked to original sources
PubMed2005

Male systemic lupus erythematosus in a Latin-American inception cohort of 1214 patients.

The objective of the study was to evaluate the influence of the male gender in the clinical presentation and outcome of systemic lupus erythematosus in a prospective inception cohort of Latin-American patients. Of the 1214 SLE patients included in the GLADEL cohort, 123 were male. Demographic characteristics as well as clinical manifestations, laboratory profile, activity and damage scores were evaluated at onset and during the course of the disease and compared with female patients. The median age at onset of the male patients was 27 and that at diagnosis 29.2 years. Delay to diagnosis was shorter in males (134 versus 185 days, P = 0.01). At onset, men more frequently showed fever (42.3 versus 27.0%, P = 0.001) and weight loss (23.6 versus 11.8%, P = 0.001). During disease course the incident of symptoms was: fever, 67.8 versus 55.6%, P = 0.012; weight loss, 47.2 versus 24.3%, P = 0.001; arterial hypertension, 37.4 versus 25.8%, P = 0.007; renal disease (persistent proteinuria and/or cellular casts), 58.5 versus 44.6%, P = 0.004); and hemolytic anemia, 19.5 versus 10.9%, P = 0.008. The laboratory results showed that: men more frequently had IgG anticardiolipin antibodies (68.2 versus 49%, P = 0.02) and low C3 (61.3 versus 48.1%, P = 0.03); 5/123 men died (4%) compared with 29/1091 women (2.7%). In conclusion, 10% of GLADEL's cohort patients were male. They showed a distinctive profile with shorter delay to diagnosis, higher incidence of fever, weight loss, arterial hypertension, renal disease, hemolytic anemia, IgG anticardiolipin antibodies and low C3. Although not statistically significant, mortality was higher in men.

Adolescent↗
PubMed1999

Frontiers of SLE: review of the 5th International Congress of Systemic Lupus Erythematosus, Cancun, Mexico, April 20-25, 1998.

OBJECTIVE: To review the recent advances in clinical and experimental research in systemic lupus erythematosus (SLE). METHODS: Review of the 5th International Congress of SLE that took place in Cancun, Mexico, on April 20-25, 1998. RESULTS: The main topics presented at the conference are summarized. These include new findings about the genetics of SLE due to fine mapping of the patients' genes and lupus mouse models, the nucleosome as a major autoantigen in SLE, serving as an immunogen for pathogenic T helper and B cells and contributing to the development of lupus nephritis, abnormalities of apoptosis as a cause of SLE, and apoptotic mechanisms as a cause of autoimmunization. Other topics included the pathophysiologic role of anti-endothelial cell antibodies in lupus with central nervous system involvement, vasculitis, the thrombotic diathesis associated with the antiphospholipid syndrome, induction of endothelial cell apoptosis and its regulation by the idiotypic network, the penetration of antinuclear antibodies to the cytoplasm and nucleus and the subsequent interaction with cellular organelles, and new aspects in the antiphospholipid syndrome, including animal models of the disease and the importance of antibodies to beta-2-glycoprotein-I and prothrombin. Advances in the clinical aspects of SLE included clinical manifestations, diagnosis, pregnancy and neonatal SLE, infections, hormones, and treatment. Additionally, four "Lectures of A Lifetime," entitled (1) What causes lupus? (2) From natural autoimmunity to autoimmune disease; (3) The idiotypic network and SLE; and (4) Late-stage morbidity and mortality in SLE-the role of accelerated atherosclerosis were presented. CONCLUSIONS: Recent advances provide new insights into the pathogenesis of SLE, as well as hope for novel therapeutic modalities and diagnostic measures. These offer the possibility of improving life quality and decreasing mortality from the disease and its complications.

Animals↗
PubMed1997

Delay in the onset of systemic lupus erythematosus following treatment with the immunomodulator AS101: association with IL-10 inhibition and increase in TNF-alpha levels.

It has recently been found that in systemic lupus erythematosus (SLE), a multisystem inflammatory disorder characterized by autoantibody production and decreased cellular immune response, increased spontaneous production of IL-10 occurs. The immunomodulator AS101 (ammonium trichloro(dioxoethylene-0,0')tellurate) was previously shown to significantly decrease IL-10 levels in cancer patients and in murine models. This study shows that AS101 inhibits the development of SLE-related autoimmune pathological manifestations. AS101 decreased the spontaneous IL-10 production by mononuclear cells from SLE patients in vitro. In vivo, systemic injection of AS101 to SCID mice transplanted with mononuclear cells from SLE patients significantly decreased serum human IL-10 levels. There was also a decrease in all serum human Ig isotypes, in anti-dsDNA, and in anti-Sm Igs. In the New Zealand Black/New Zealand White/F1 model, AS101 significantly increased serum TNF-alpha and IFN-gamma while decreasing IL-10 levels; these changes were accompanied by a rapid decrease in anti-dsDNA and anti-ssDNA Igs. More importantly, continuous treatment of New Zealand Black/New Zealand White/F1 mice with AS101 for 6 mo led to the development of proteinuria in 30% of the treated mice compared with 100% in PBS-treated mice (p < 0.001). AS101 treatment reduced the level of immmune complex deposition in the glomeruli, prevented glomerular hypercellularity and mesangial expansion and led to a much smaller mean glomerular volume in treated mice (185 +/- 6 vs 428 +/- 47.103 microm3; p < 0.01). We suggest that treatment with a nontoxic immunomodulator such as AS101, previously used in phase II trials on cancer patients, may be an effective therapeutic approach for controlling SLE.

Adjuvants, Immunologic↗
PubMed1997

Dysregulation of interleukin-10 production in relatives of patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate interleukin-10 (IL-10) production in relatives of patients with systemic lupus erythematosus (SLE). METHODS: Production of IL-10 was evaluated in 13 families in which several members had SLE. The constitutive IL-10 production in SLE patients (n = 16) was compared with that in healthy members of these multiplex families (n = 70), in 30 SLE patients who had no relatives with SLE, and in 46 healthy unrelated controls. RESULTS: The level of IL-10 production did not differ between SLE patients who were members and those who were not members of multiplex families (mean +/- SEM 4,384 +/- 908 pg/ml and 4,709 +/- 560 pg/ml, respectively), but was higher in both groups than in healthy unrelated controls (515 +/- 88 pg/ml). The healthy members of the multiplex families constitutively produced large amounts of IL-10 (3,080 +/- 311 pg/ml; P < 0.001 compared with healthy unrelated controls). This high IL-10 production was independent of age and sex, and was similar in first- and second-degree relatives of SLE patients. The IL-10 was produced both by monocytes and by a subpopulation of B lymphocytes in SLE patients and in their relatives. CONCLUSION: The dysregulation of IL-10 production previously identified in SLE patients is also present in healthy members of families with several cases of SLE, and it may contribute to the immunologic abnormalities affecting relatives of SLE patients.

Age Factors↗
PubMed1997

The antiphospholipid/cofactor syndromes. II. A variant in patients with systemic lupus erythematosus with antibodies to beta 2-glycoprotein I but no antibodies detectable in standard antiphospholipid assays.

OBJECTIVE: After the initial description of the anticardiolipin syndrome inpatients with systemic lupus erythematosus (SLE), it became clear that phospholipids other than cardiolipin could also be involved, that there could also be a primary syndrome, and that protein cofactors participate in in vitro reactivity of the autoantibodies. We describe 5 patients with SLE with clinical manifestations of antiphospholipid syndrome (APS) but persistently negative antiphospholipid antibodies (aPL). In all their tested sera we found antibodies to phospholipid-free beta 2-glycoprotein I (a beta 2-GPI). METHODS: We studied 5 patients with SLE with at least 2 clinical manifestations of APS with no serum aPL detected in routine assays. IgG and IgM a beta 2-GPI were studied by ELISA and by Western blot. We also tested for antibodies to phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine by ELISA. We studied 54 normal sera as controls. RESULTS: Four patients had livedo reticularis, 2 had thrombocytopenia, 2 had hemolytic anemia, and one each had recurrent venous thromboses, repeated fetal loss, pulmonary arterial hypertension, and transverse myelitis. No patient had serum aPL, but all had high titers of IgG a beta 2-GPI (p < 0.001 vs controls). Reactivity found in ELISA was confirmed by Western blot. CONCLUSION: We describe a variant of APS in patients with SLE with negative aPL but serum antibodies to beta 2-GPI.

Adult↗
PubMed1997

HLA class I and class II alleles and haplotypes in Mexican mestizos established from serological typing of 50 families.

We describe new information on the frequency and association of class II antigens (HLA-DR and HLA-DQ) of the major histocompatibility complex (MHC) in Mexicans. The study includes HLA-B typing and its association with the HLA-DR antigens determined in 50 families, which included 100 individuals. This family study allowed the establishment of the precise composition of the 200 HLA haplotypes, which cannot be obtained from unrelated individuals. The predominant antigens in decreasing order of frequency were B35, B39, and B61 at the B locus; DR4, DR5, and DR8 at the DR locus; and DQ3 at the DQ locus. The most common HLA-B,HLA-DR haplotype (considering broad specificities) was B16,DR4, with a frequency of 8.0%. Five HLA-B,HLA-DR haplotypes showed significant delta values (observed vs. expected frequencies) after correcting for the number of comparisons. On the other hand, the most common HLA-DR,HLA-DQ haplotypes were DR4,DQ3 and DR5,DQ3 with a frequency higher than 10%. Ten of the 17 HLA-DR,HLA-DQ haplotypes had significant postcorrection delta values.

Ethnicity↗
PubMed1996

Epitope mapping and reactivity of autoantibodies to the E2 component of 2-oxoglutarate dehydrogenase complex in primary biliary cirrhosis using recombinant 2-oxoglutarate dehydrogenase complex.

Five different target mitochondrial autoantigens recognized by sera from patients with primary biliary cirrhosis (PBC) have been identified as subunits of the following 2-oxo acid dehydrogenase complexes: the pyruvate dehydrogenase complex (PDC), the branched chain 2-oxo acid dehydrogenase complex (BCOADC), and the 2-oxoglutarate dehydrogenase complex (OGDC). Unlike the E2 subunits of PDC (PDC-E2) and BCOADC (BCOADC-E2), the E2 subunits of OGDC (OGDC-E2) reactivity of PBC sera and the reactive epitope of OGDC-D2 have not hitherto been studied in detail. In this report, we took advantage of a recombinant fusion protein for OGDC-E2 to address these issues. Eighty of 268 (29.9%) PBC patient sera but none of the 45 controls reacted with recombinant OGDC-E2. The recombinant OGDC-E2 was judged to express the immunodominant epitope, because when sera from patients with PBC were preabsorbed with the recombinant fusion protein, such sera were depleted of reactivity against 48 kD OGDC-E2 when probed on beef heart mitochondria (BHM) but retained reactivity toward PDC-E2 and/or BCOADC-E2. Furthermore, affinity-purified PBC sera against recombinant OGDC-E2 reacted only with native OGDC-E2 and not with any other enzyme components of the 2-oxo acid dehydrogenase complex. Antimitochondrial autoantibodies (AMA) against OGDC-E2 included immunoglobulin (Ig)G2, IgG3 and IgM and the relative titers were as follows: IgG2 > IgG3 > IgM. Finally, using overlapping recombinant polypeptides, it was determined that a minimum of 81 amino acids (residues 67-147) corresponding to the lipoyl domain of OGDC-E2 are necessary for reactivity, suggesting that a conformational autoepitope is recognized by AMA. These data suggest that each of the 2-oxo acid dehydrogenase enzymes has distinct antigenicity despite their similarities in structure and function. The availability of recombinant OGDC-E2 autoantigen will allow the design of additional studies to further our understanding of the role of mitochondrial autoantigens in the pathogenesis of PBC.

Animals↗
PubMed1996

The antiphospholipid/cofactor syndromes: a primary variant with antibodies to beta 2-glycoprotein-I but no antibodies detectable in standard antiphospholipid assays.

BACKGROUND: Most systemic lupus erythematosus (SLE) patients with two or more clinical manifestations of the antiphospholipid syndrome (APS) and negative antiphospholipid antibodies (aPL) have antibodies to beta 2-glycoprotein-I (a beta 2 GP-I). Herein we describe a similar set of circumstances, but in patients without evidence of SLE. PATIENTS AND METHODS: We studied 6 patients with recurrent venous and/or arterial thromboses without aPL as detected by routine assays nor clinical or serological evidence of other autoimmune disease. Immunoglobin (Ig) G and IgM antibodies to bovine and human phospholipid-free beta 2 GP-I were studied by Western blot test and by enzyme-linked immunosorbent assay (ELISA) utilizing radiated and nonirradiated plates. We also tested antibodies to cardiolipin, phosphatidylserine, and phosphatidylethanolamine by ELISA. As controls, 54 normal sera were studied. RESULTS: All 6 patients had recurrent arterial and/or venous thromboses. Three also had thrombocytopenia, 1 had livedo reticularis, and 2 had valvular heart disease. None of the patients had aPL, but all had serum IgG reactivity against human and bovine beta 2 GP-I (P < 0.001 versus controls for both). Titers of anti-bovine beta 2 GP-I were higher when studied in irradiated plates but were also higher than normal in nonirradiated plates (P < 0.001). These antibodies did not recognize human or bovine beta 2 GP-I bound to cardiolipin in solid phase. We confirmed by Western blot that these autoantibodies recognize human beta 2 GP-I. We found no IgM a beta 2 GP-I. CONCLUSIONS: We describe a primary condition akin to the antiphospholipid syndrome with negative aPL, but with serum IgG antibodies to human and bovine beta 2 GP-I. These antibodies recognize beta 2 GP-I epitopes that are not accessible when beta 2 GP-I is bound to cardiolipin.

Adult↗
PubMed1996

Systemic lupus erythematosus in males. A study of 107 Latin American patients.

Clinical and laboratory features were analyzed in 107 Latin American male patients with systemic lupus erythematosus (SLE) who were compared with a group of 1,209 Latin American female patients with SLE to determine the presence of gender-associated differences. Males had an increased prevalence of renal disease, vascular thrombosis, and the presence of anti-dsDNA antibodies, as well as the use of moderate to high doses of corticosteroids, compared with female SLE patients. Although there was no difference in mortality from all causes, SLE-related mortality was higher in the male group. All these findings are consistent with a more severe disease in Latin American males than in female patients from the same region.

Adolescent↗
PubMed1995

Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus.

Interleukin-10 (IL-10) is produced at a high level by B lymphocytes and monocytes of patients with systemic lupus erythematosus (SLE). In the present work, we analyzed whether this increased production of IL-10 contributed to the abnormal production of immunoglobulins (Ig) and of autoantibodies in SLE. The role of IL-10 was compared with that of IL-6, another cytokine suspected to play a role in these abnormalities. The spontaneous in vitro production of IgM, IgG, and IgA by peripheral blood mononuclear cells from SLE patients was weakly increased by recombinant IL (rIL)-6, but strongly by rIL-10. This production was not significantly affected by an anti-IL-6 mAb but was decreased by an anti-IL-10 mAb. We then tested the in vivo effect of these antibodies in severe combined immunodeficiency mice injected with PBMC from SLE patients. The anti-IL-6 mAb did not significantly affect the serum concentration of total human IgG and of anti-double-stranded DNA IgG in the mice. In contrast, the anti-IL-10 mAb strongly inhibited the production of autoantibodies, and, to a lesser extent, that of total human IgG. These results indicate that the Ig production by SLE B lymphocytes is largely IL-10 dependent, and that the increased production of IL-10 by SLE B lymphocytes and monocytes may represent a critical mechanism in the emergence of the autoimmune manifestations of the disease.

Adult↗
PubMed1995

Serum antibodies to distinct epitopes of the tissue-type plasminogen activator (t-PA) in patients with systemic lupus erythematosus.

Defective fibrinolysis due to decreased tissue-type plasminogen activator (t-PA) activity is a well-established finding in patients with systemic lupus erythematosus (SLE). The possibility that this decrease in t-PA activity may be related to the presence of autoantibodies directed against t-PA, and the possible role of these autoantibodies in the pathophysiology of fibrinolysis in SLE, were investigated. Serum samples from 115 SLE patients and 63 normal volunteers were analyzed for the presence of such antibodies. The search for antibodies to t-PA was performed by means of several systems, allowing for the identification of epitopes presented in different conformational physical states of t-PA: free or associated to its inhibitor (PAI-1) in plasma, specifically bound to fibrin surface, or passively adsorbed to solid supports. Antibodies in variable amounts were detected by all systems used; however, t-PA activity was not inhibited by the IgG fraction of the positive sera in a fibrin-agar fibrinolysis system. Moreover, the demonstration of serum anti-t-PA antibodies was not associated with clinical or laboratory abnormalities related to vasoocclusive episodes. These results indicate that, as in the case of other autoantibodies, their detection in serum does not imply their direct participation in the pathophysiology of thrombosis in SLE.

Adolescent↗
PubMed1995

Anti-neuronal antibodies in antiphospholipid syndrome with central nervous system involvement: the difference from systemic lupus erythematosus.

The presence of antineuronal antibodies was compared in 43 patients with primary aPLS and 57 patients with neuropsychiatric SLE. Fifty-eight patients with Guillain-Barré syndrome and 72 normal healthy donors served as control groups. Seventeen patients in the study group had aPLS associated with CNS involvement. Antineuronal antibodies were studied in the sera employing a novel flow cytometric assay. The frequency of antineuronal antibodies in patients with aPLS and CNS involvement was not significantly different from that of patients with aPLS without CNS disease or from that found in the control groups (12%, 19% and 7%, respectively). However, it was significantly different from that found in SLE patients with CNS involvement (60%) (P < 0.001). Our results provide further evidence that unlike CNS-SLE, the major mechanism of CNS involvement in patients with primary aPLS might not be autoantibody (antineuronal) mediated, but rather 'thrombotic' in origin, or due to yet unknown factors.

Antiphospholipid Syndrome↗
PubMed1994

Effect of CD28 antibody on T cells from patients with systemic lupus erythematosus.

CD28 is a 44-kDa glycoprotein that contributes to T cell activation and proliferation. To elucidate the functional role of CD28 in T cell proliferation and IL-2 production in SLE, we studied its effects in cells from untreated patients with active (n = 10) or inactive disease (n = 10) as compared with normal subjects. Mean percentages of CD4+ CD28+ and CD8+ CD28+ T cells were decreased in SLE patients (P < 0.01). SLE patients had significantly decreased absolute CD8+ CD28+ T cells. To investigate whether CD28 antibody affects T cell proliferation, we stimulated peripheral blood T cells from SLE patients and normal controls with anti-CD28, anti-CD3 and/or Interleukin-2 (IL-2) during 3 days of culture. We found that T cells from SLE patients had significantly higher responses to CD28 than did cells from normal controls. This effect was higher in cells from patients with active disease than in those with inactive disease. Conversely, IL-2 had no significant effect on the proliferative response of SLE T cells. However, when it was used for co-stimulating with anti-CD28, there was an increase in the secretion of IL-2 which was greater in the cells of patients with active disease. Thus, on average, there was an 81% increase in the production of IL-2 in T cells from patients with active SLE, 48% in those from patients with inactive disease and 40% in T cells from healthy controls, as compared with the production in response to stimulus by anti-CD3 or with anti-CD3 and anti-CD28. Lymphocytes from patients with active disease showed increased gene expression of CD28 when compared with normal subjects. These data suggest that CD28 might play a central role in the defective immune response observed in SLE patients.

Adult↗