RESUMEN
BACKGROUND: Chikungunya (CHIKV) and dengue viruses (DENV) are two arboviruses with epidemic potential and similar clinical presentations. The potential life-threatening risk associated with DENV justifies an immediate biological assessment and medical follow-up which may be delayed for CHIKV. OBJECTIVES: To compare the clinical variables that would help differentiate patients infected with CHIKV or DENV, and then to compute a predictive score. PATIENTS AND METHOD: Retrospective case-control study comparing CHIKV-infected patients diagnosed by RT-PCR in 2014 with patients infected with DENV diagnosed by positive NS1 antigen test in 2013. Children aged<15 years and pregnant women were excluded. Clinical and biological variables were compared, and a multivariate analysis was performed. A clinical score was developed using the ß coefficients to differentiate the infections. RESULTS: Over the study period 168 patients infected with CHIKV were compared with 452 patients with DENV. The clinical variables independently associated with CHIKV was joint and back pain, and those associated with DENV were headache, muscle pain, nausea/vomiting, diarrhea, and hemorrhagic signs. The clinical score had 98% sensitivity for DENV and a ROC curve of 0.96. CONCLUSION: These two infections have a similar clinical presentation but the use of the proposed clinical score during the acute phase of the disease would make it possible to identify cases of DENV during a CHIKV epidemic to suggest adequate patient management.
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Fiebre Chikungunya/diagnóstico , Fiebre Chikungunya/epidemiología , Dengue/diagnóstico , Dengue/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Coinfección/epidemiología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Proyectos de Investigación , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
The pathogenic role of antiendothelial cell antibodies (AECA) remains unclear. They are frequently associated with antibodies to anionic phospholipids (PL), such as phosphatidylserine (PS), which is difficult to reconcile with the distribution of PL molecular species within the plasma membrane. Since it is already known that PS is transferred to the outer face of the membrane as a preclude to apoptosis, the possibility exists that apoptosis is initiated by AECA. AECA-positive/anti-PL antibody-negative sera from eight patients with systemic sclerosis (SS) and 21 control patients were evaluated. Endothelial cells (EC) were incubated with AECA and the exposure of PS was established through the binding of annexin V. Hypoploid cell enumeration, DNA fragmentation, and optical and ultrastructural analyses of EC were used to confirm apoptosis. Incubation of EC with AECA derived from six of eight patients with SS led to the expression of PS on the surface of the cells. This phenomenon was significantly more frequent in SS (P < 0.04) than in control diseases. The redistribution of plasma membrane PS preceded other events associated with apoptosis: hypoploidy, DNA fragmentation, and morphology characteristic for apoptosis. Apoptosis-inducing AECA did not recognize the Fas receptor. We conclude that AECA may be pathogenic by inducing apoptosis.
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Apoptosis/inmunología , Autoanticuerpos/sangre , Endotelio Vascular/inmunología , Esclerodermia Sistémica/inmunología , Anexina A5/metabolismo , Antígenos de Superficie/inmunología , Apolipoproteínas/metabolismo , Membrana Celular/química , Células Cultivadas , Enfermedades del Tejido Conjuntivo/fisiopatología , Fragmentación del ADN/fisiología , Citometría de Flujo , Glicoproteínas/metabolismo , Histocitoquímica , Humanos , Microscopía Electrónica , Fosfatidilserinas/metabolismo , Fosfolípidos/inmunología , beta 2 Glicoproteína IRESUMEN
BACKGROUND: Systemic sclerosis (SS) encompasses a wide spectrum of clinical presentations. Antiendothelial cell antibodies (AECA) in patients with primary Raynaud's phenomenon (PRP), limited SS (lSSc), or diffuse SS (dSSc) may help to determine the long-term prognosis of the disease. METHODS: Twenty-seven normal controls, 13 patients with PRP, 36 with lSSc, and 31 with dSSc were included in the study. Sera were examined for the presence of AECA, using a cellular enzyme-linked immunosorbent assay (ELISA). Angiotensin-converting enzyme (ACE) activity, plasma von Willebrand factor antigen (vWfAg), and thrombomodulin (Tm) concentrations were also evaluated. The medical records of 50 of the lSSc and dSSc patients were reviewed and the organ system involvement noted. RESULTS: Antiendothelial cell antibodies were present in 3 patients with PRP, 16 patients with lSSc, and 26 patients with dSSc. These autoantibodies were mainly of the IgG isotype. There was no difference in ACE activity between patients and controls. In contrast, vWfAg and Tm concentrations were higher in patients with PRP relative to controls, and higher in patients with lSSc compared with those with PRP. The presence of AECA was associated with digital scars and ulcers (P < 0.004 and P < 0.003, respectively), severe RP (P < 0.01), grade 3 tortuosity of vessels (P < 0.0004), and lung involvement (P < 0.02). CONCLUSION: The significant trend for AECA to increase with disease severity across the three groups of patients studies suggests that the AECA test can identify subsets of SSc with differing prognoses.
Asunto(s)
Autoanticuerpos/análisis , Biomarcadores/análisis , Endotelio Vascular/inmunología , Esclerodermia Sistémica/diagnóstico , Adolescente , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peptidil-Dipeptidasa A/sangre , Enfermedad de Raynaud/sangre , Enfermedad de Raynaud/diagnóstico , Enfermedad de Raynaud/inmunología , Esclerodermia Localizada/sangre , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/inmunología , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/inmunología , Trombomodulina/sangre , Factor de von Willebrand/análisisRESUMEN
The sera patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) were tested, by ELISA, for antibodies to phosphatidylethanolamine (aPE), as well as to cardiolipin (aCL) and compared to healthy blood donors (HBD). Both, SLE and APS patients presented a higher titre of IgM-aPE antibodies than normals, while the IgG and IgA aPE reactivity did not differ. APS patients were characterized by higher IgM-aPE antibody titres than SLE patients. In contrast, the predominant isotype of aCL antibodies in APS patients was IgG. The IgM aPE reactivity was correlated with IgM aCL reactivity, while no correlation was observed between the total IgM values and IgM-aPE binding units of sera tested. Since it was shown that beta 2-glycoprotein-I (beta 2-GPI) contributes to a complex antigen by binding to phospholipids and that this antigen is recognized by antiphospholipid antibodies from autoimmune patients, sera beta 2-GPI levels were measured and correlated to aCL and APE activity. Although APS patients had higher beta 2-GPI levels than SLE patients, no correlation was found between the beta 2-GPI levels and IgG/IgM aCL and IgM-aPE reactivities a finding suggesting that in addition to beta 2-GPI, other cofactors for aPE antibodies may exist. These findings indicate that aPE and aCL antibodies co-exist and that the IgM-isotype is predominant in APS. In addition, the IgA and IgG aPE antibodies appear to occur in low titres in these patients, as well as in normals and may exist as natural autoantibodies. We suggest that the high IgM-aPE antibodies may be viewed as a thymus independent process.
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Anticuerpos Anticardiolipina/sangre , Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/inmunología , Glicoproteínas/análisis , Isotipos de Inmunoglobulinas/sangre , Lupus Eritematoso Sistémico/inmunología , Fosfatidiletanolaminas/inmunología , Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/sangre , Ensayo de Inmunoadsorción Enzimática , Humanos , Isotipos de Inmunoglobulinas/inmunología , Lupus Eritematoso Sistémico/sangre , beta 2 Glicoproteína IRESUMEN
Sera from patients with giant cell arteritis and/or polymyalgia rheumatica were tested for the presence of IgG, IgM and IgA antibody to endothelial cells (AEC), cardiolipin (ACL) and phosphatidylethanolamine (APE) using enzyme-linked immunosorbent assays. There were strong correlations between ACL and APE, but also between AEC and ACL IgM (p < 0.02) and between AEC and APE IgA (p < 0.003). Inhibition of AEC binding was achieved by absorption onto EC, but ACL and APE binding was also significantly reduced. In contrast, the binding of AEC antibody could not be inhibited by incubation with CL. Our data suggest that AEC constitute a heterogeneous population of autoantibodies.
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Anticuerpos Antifosfolípidos/sangre , Autoanticuerpos/sangre , Endotelio Vascular/inmunología , Arteritis de Células Gigantes/inmunología , Polimialgia Reumática/inmunología , Anciano , Anciano de 80 o más Años , Células Cultivadas , Reacciones Cruzadas , Femenino , Arteritis de Células Gigantes/sangre , Humanos , Masculino , Persona de Mediana Edad , Fosfatidiletanolaminas/inmunología , Polimialgia Reumática/sangre , Cordón Umbilical/inmunologíaRESUMEN
The polymerase chain reaction (PCR) was used to search for hepatitis B virus (HBV) DNA sequences in the sera of 51 dialyzed patients (26 women, 25 men; mean age 60.5 years, range 35 to 85). Two different sets of specific primers for HBV core and surface gene sequences were synthesized and used for each sample. Controls were 90 HBV negative blood donors. Results were analyzed according to other serological markers of HBV. Among the eight HBsAg positive patients (anti-HBc+: 8/8), seven were positive for HBV DNA. Four of eight patients were vaccinated but later developed acute HBs hepatitis. The presence of HBV DNA was detected in six of 43 HBsAg negative patients (anti-HBc+: 5/6; anti-HBs+: 3 of 6; HBeAg: 0 of 6; anti-HBe: 2 of 6). These six patients were vaccinated and four of six developed mild and transient cytolytic hepatitis (3 before vaccination; 2 later). These results showed that HBsAg seronegative patients can be infectious. The role of HBV vaccination and/or the existence of variations in the structure of the viral genome is discussed.
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ADN Viral/análisis , Virus de la Hepatitis B/genética , Reacción en Cadena de la Polimerasa , Diálisis Renal/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Femenino , Antígenos de Superficie de la Hepatitis B/análisis , Vacunas contra Hepatitis B/inmunología , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , VacunaciónRESUMEN
Rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren's syndrome are nonorgan-specific autoimmune diseases in which serum monoclonal immunoglobulins (MIg) have been identified repeatedly. Conversely, autoimmune traits have been detected in a number of patients with lymphoproliferative disorders such as multiple myeloma, Waldenström's macroglobulinemia and chronic lymphocytic leukemia. The latter cells have even shown to produce multispecific autoantibodies. One connection between connective tissue diseases and Iymphoid malignancies might be established by a limitedfraction of B Iymphocytes expressing the CD5 marker.
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Enfermedades Autoinmunes/inmunología , Paraproteinemias/inmunología , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/complicaciones , Linfocitos B/inmunología , Linfocitos B/patología , Antígenos CD5/inmunología , Humanos , Paraproteinemias/sangre , Paraproteinemias/complicacionesRESUMEN
Since there is no information regarding the glycosylation status of immunoglobulin A (IgA) in patients with primary Sjögren's syndrome (pSS), the sialic acid and galactose contents of IgA1 and IgA2 were evaluated in 17 pSS patients and in 14 normal controls (NC), using new enzyme-linked immunosorbent assays. The proportion of sialylated IgA1 and IgA2 was augmented (p < 0.001 and < 0.05, compared with NC), whereas that of galactosylated IgA1 and IgA2 was reduced (p < 0.01 and < 0.02, respectively). The level of SA IgA1 correlated the amount of IgA-containing immune complexes (p < 0.01), serum IgA (p < 0.01) and IgA-rheumatoid factor (p < 0.01). This demonstrates a number of IgA abnormalities in pSS patients. There were no correlations between SA and Gal, however, nor could any difference be ascribed to extraglandular manifestations.
Asunto(s)
Inmunoglobulina A/sangre , Inmunoglobulina A/química , Síndrome de Sjögren/inmunología , Adulto , Anciano , Femenino , Galactosa/análisis , Glicosilación , Humanos , Masculino , Persona de Mediana Edad , Ácido N-Acetilneuramínico , Ácidos Siálicos/análisisRESUMEN
Patients with Sjögren's syndrome (SS) display two sets of immunological abnormalities. B cells are oligoclonally activated, resulting in hypergammaglobulinaemia, elevated levels of circulating immune complexes (CIC) and non-organ specific autoantibodies. The cellular arm of the immune response is also involved, as shown by the predominance of activated T cells within the exocrine gland infiltrate. IgA could well bridge the gap between activated B cells and defective T cells and by doing so, play a pivotal role in the pathogenesis of SS. This interpretation is supported by the high proportion of IgA in immunoglobulin(Igl) production at the mucosal level. Additionally, IgA is the Igl class most dependent on T cell help. A number of studies over the past 15 years have reported high levels of serum and secretory IgA, IgA-rheumatoid factor and IgA-containing CIC. A correlation between disease activity and the latter abnormalities has recently been shown. There is, however, a need for longitudinal assessment of total IgA and IgA autoantibodies in order to further evaluate their role in the pathogenesis of the disease.
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Inmunoglobulina A/análisis , Síndrome de Sjögren/inmunología , Complejo Antígeno-Anticuerpo/análisis , Humanos , Factor Reumatoide/análisis , Saliva/química , Síndrome de Sjögren/sangreRESUMEN
OBJECTIVE: There is still great uncertainty in the detection of antiendothelial cell antibodies (AECA). The aim of our study was to compare the results obtained using different methods. METHODS: Sera were obtained from 71 patients with a variety of vasculitides. Three assay methods were used: cell ELISA, flow cytometry (FACS) and Western blot (WB). RESULTS: In the ELISA 12/17 patients with systemic lupus erythematosus (SLE), 1/12 with Churg Strauss (CS) disease, 3/12 with micropolyarteritis (MPA) and 5/30 with Wegener's granulomatosis (WG) tested positive. Most of the sera that were positive on ELISA were not by FACS. Among the negative sera, 50% of WG, 40% of MPA, 20% of CS and 40% of SLE became positive on WB. There were some specific patterns of reactivity for a given disease, so that some bands could be assigned to a disease. CONCLUSION: The discrepancies in the results may most probably be accounted for by differences between the antigenic preparations. Caution must thus be exercised when interpreting the results of any of these three tests.
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Autoanticuerpos/análisis , Endotelio Vascular/inmunología , Vasculitis/diagnóstico , Vasculitis/inmunología , Arteritis/diagnóstico , Arteritis/inmunología , Autoanticuerpos/sangre , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Western Blotting , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/inmunología , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/inmunología , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina G/sangre , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunologíaRESUMEN
Three preliminary concepts are developed: antigen presentation, "peptidic self" and superantigen. Several infectious contenders for rheumatoid arthritis (RA) are then reviewed: Epstein-Barr virus, mycobacteria, parvovirus, proteus and streptococcus. Finally, the most important hypotheses are discussed: microbe present and still accessible, microbe present but hidden, microbe absent but perpetuated by the immune system. In the latest case, molecular mimicry could possibly be the mechanism operating in RA.
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Presentación de Antígeno , Artritis Infecciosa/microbiología , Artritis Reumatoide/microbiología , Herpesvirus Humano 4/patogenicidad , Mycobacterium/patogenicidad , Animales , Artritis Infecciosa/inmunología , Artritis Reumatoide/inmunología , Autoantígenos/inmunología , Modelos Animales de Enfermedad , Femenino , Herpesvirus Humano 4/inmunología , Humanos , Masculino , Mycobacterium/inmunología , Ratas , Superantígenos/fisiologíaAsunto(s)
Congresos como Asunto , Internado y Residencia , Médicos , Medicina Tropical , Enfermedades Transmisibles Emergentes/diagnóstico , Enfermedades Transmisibles Emergentes/patología , Enfermedades Transmisibles Emergentes/terapia , Congresos como Asunto/organización & administración , Educación Médica/organización & administración , Educación Médica/normas , Guyana Francesa , Humanos , Internado y Residencia/normas , Malaria Vivax/epidemiología , Malaria Vivax/patología , Malaria Vivax/terapia , Médicos/normas , Médicos/estadística & datos numéricos , Medicina Tropical/organización & administración , Medicina Tropical/tendencias , UniversidadesRESUMEN
The in vivo immune effects of nine beta (beta)-blockers are studied in C5B1/6 mice after 7 days of treatment. Humoral and cellular studies indicate that several beta-blocking agents, particularly pindolol and acebutolol, may induce a polyclonal activation of lymphocytes. It may involve all the classes and subclasses of immunoglobulins with a preferential effect on IgA and IgG2a. Further investigations, conducted using the laevorotatory and dextrorotatory forms of pindolol indicate that this immune effect is not mediated by specific beta-adrenergic receptors.
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Antagonistas Adrenérgicos beta/farmacología , Activación de Linfocitos/efectos de los fármacos , Acebutolol/farmacología , Animales , Femenino , Inmunidad Celular/efectos de los fármacos , Inmunoglobulinas/metabolismo , Ratones , Ratones Endogámicos C57BL , Pindolol/farmacología , Receptores Adrenérgicos beta/efectos de los fármacos , Receptores Adrenérgicos beta/inmunología , EstereoisomerismoRESUMEN
The CD5 molecule is expressed by most T cells but it is present on a minor B cell subset. Whilst several studies have provided information on the physiological role of T cell CD5, the functional role of CD5 on B lymphocytes remains unclear. To address this question, tonsillar CD5+ B cells were sorted by dual-colour fluorescence and FACS. Sorted cells were stimulated with polyclonal anti-IgM antibodies (Ab), and monoclonal (MoAb) F(ab')2 fragments of anti-CD5. Proliferative responses were evaluated by enumeration of Ki-67 positive cells using quantitative flow cytometry. Co-stimulation with anti-CD5 MoAb for 3 days did not affect the anti-IgM and IL2-induced proliferation of CD5+ B cells. This was seen under conditions where the anti-CD5 was soluble, adsorbed to the microwells or cross-linked by anti-mouse antibodies. Fewer CD25+ cells were detected, however, in the presence of anti-CD5. In contrast, the proliferative response of CD5+ B cells prestimulated for 3 days with IL-2 and anti-IgM, was sustained in a further 3-day culture period when anti-CD5 was added. It is concluded that CD5 occupancy might provide an additional signal to activated CD5+ B cells favouring their proliferation and differentiation into autoantibody secreting cells.
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Antígenos CD/inmunología , Linfocitos B/inmunología , Activación de Linfocitos/inmunología , Anticuerpos/inmunología , Anticuerpos/farmacología , Linfocitos B/citología , Antígenos CD5 , Adhesión Celular/efectos de los fármacos , Adhesión Celular/inmunología , Células Cultivadas , Niño , Humanos , Inmunoglobulina M/inmunología , Inmunoglobulina M/farmacologíaRESUMEN
Several sets of data suggest that specific classes of anti-DNA antibodies could be implicated in the genesis of glomerular lesions in SLE. The goal of this work is to investigate if this pathogenic role could be related to the antibodies' genetic origin--from BALB/c or NZBxNZW/F1 mice--or to their physiological origin--induced either by DNA or by polyclonal B cell activation in normal mice. For this purpose, anti-DNA antibody hybridoma clones produced from different origins were subcutaneously injected in BALB/c or NZBxNZW/F1 female mice, followed by studies of immunological parameters and kidney lesions. Results concur that the induced anti-DNA antibodies can play a role in fatal disease development, related to clonal specificity but not to the way of stimulation which was either polyclonal B cell activation or DNA immunization. Also, they emphasize the possible very lethal role of serum circulating DNA.
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Anticuerpos Antinucleares/administración & dosificación , ADN/inmunología , Hibridomas/trasplante , Lupus Eritematoso Sistémico/inmunología , Enfermedad Aguda , Animales , Anticuerpos Antinucleares/genética , Anticuerpos Antinucleares/inmunología , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/inmunología , Complejo Antígeno-Anticuerpo/análisis , Linfocitos B/inmunología , Células Clonales , Femenino , Técnica del Anticuerpo Fluorescente , Inmunoglobulinas/análisis , Inyecciones Subcutáneas , Riñón/patología , Lupus Eritematoso Sistémico/genética , Activación de Linfocitos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NZBRESUMEN
Cyclophosphazenic compounds bearing ethylene-imino groups are cytocydal chemicals which can modulate polyclonal activation of lymphocytes (PAL) and prevent the development of murine lupus. The effects on PAL of the different parts of these chemicals and of vectorization by polyamines have been investigated by treating lipopolysaccharide injected C57Bl/6 mice with various cyclophosphazenic compounds and thiotepa. The immune effects of the cyclophosphazenic substances have been found to be mediated by ethylene-imino groups and to be modulated by polyamine vectorization. These compounds might represent a new class of drugs for treatment of immune mediated diseases of the lupus type.
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Adyuvantes Inmunológicos/farmacología , Aziridinas/farmacología , Imidas/farmacología , Activación de Linfocitos/efectos de los fármacos , Compuestos Organofosforados/farmacología , Animales , Relación Dosis-Respuesta a Droga , Etilenos/farmacología , Femenino , Iminoácidos/farmacología , Ratones , Poliaminas/farmacología , Relación Estructura-ActividadRESUMEN
Cellular and humoral parameters of the polyclonal stimulation of lymphocytes induced by a single injection of bacterial lipopolysaccharide were determined in 6-11 week-old C57B1/6 mice at various periods of time. The study of cellular parameters on day 5 in 8-10 week-old mice appears to be suitable to quantify the induced polyclonal stimulation. Cyclophosphamide was shown to inhibit it, particularly when the drug was given the day or one day after the injection of lipopolysaccharide, and a dose dependent effect was observed. This model may be useful for the selection, and the immunopharmacological study, of drugs able to modulate a polyclonal stimulation of B lymphocytes.
Asunto(s)
Linfocitos B/inmunología , Activación de Linfocitos/efectos de los fármacos , Modelos Biológicos , alfa-Macroglobulinas/farmacología , Animales , Formación de Anticuerpos/efectos de los fármacos , Células Productoras de Anticuerpos/inmunología , Células Productoras de Anticuerpos/metabolismo , Linfocitos B/metabolismo , Ciclofosfamida/farmacología , Femenino , Inmunoglobulinas/biosíntesis , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos C57BLRESUMEN
OBJECTIVE: To determine the relevance of the functional affinity of IgM rheumatoid factor (RF) to the clinical and serological characteristics of patients with rheumatoid arthritis. METHODS: The functional affinity of IgM RF of 57 seropositive rheumatoid arthritis patients was evaluated by an enzyme linked immunosorbent assay based on the use of a chaotropic agent. The inhibition index was taken as an estimate of functional affinity. The patient group was divided into high functional affinity subgroup 1 (functional affinity < 0.5, n = 37) and low functional affinity subgroup 2 (functional affinity > 0.5, n = 20). The medical records of all patients were reviewed with a particular note of the disease activity and the articular damage score. RESULTS: The disease duration was shorter (P < 0.01) in subgroup 1 patients [7.9 (SD 6.4) years] than in subgroup 2 patients [13.4 (11.29) years], so that Ritchie's, Lee's, and Steinbrocker's indices were lower in the former than in the latter (P < 0.01, 0.001, and 0.01, respectively). In contrast, erythrocyte sedimentation rates, C reactive protein concentrations, antinuclear antibody, and HLA DR4 prevalences were similar in the two subgroups. CONCLUSIONS: Different forms of RF are present during progression of the disease.