[Intravenous immunoglobulin therapy: ELISA measurement of antidesmogleins 1 and 3 in three patients with pemphigus vulgaris]. / Terapia con inmunoglobulinas intravenosas: medición seriada mediante ELISA de anticuerpos antidesmogleína 1 y 3 en tres pacientes con pénfigo vulgar.

Intravenous immunoglobulin therapy (IVIg) has been used in the treatment of autoimmune bullous diseases unresponsive to conventional therapy in recent years. The action mechanism, which is not well known, suggests a wide spectrum of immunoregulation. In the last five years, several studies on patients with unresponsive pemphigus vulgaris with a clinical and serological outcome after IVIg administration in 80%-90% of cases have been published. We report the case of 3 patients with pemphigus vulgaris in whom we measured autoantibody titers to desmoglein 3 and 1 during 8 months. In spite of the clinical improvement, no significant decrease in antibody concentration was observed. Therapy with IVIg, although it has clinical benefit, did not decrease antibody values in our patients and thus it may need to be combined with immunosuppressant that inhibit pathogen antibody production.

Terapia con inmunoglobulinas intravenosas: medición seriada mediante ELISA de anticuerpos antidesmogleína 1 y 3 en tres pacientes con pénfigo vulgar / Intravenous immunoglobulin therapy: ELISA measurement of antidesmogleins 1 and 3 in three patients with pemphigus vulgaris

La terapia con inmunoglobulinas intravenosas (IgIV) es utilizada en los últimos años en pacientes con enfermedades ampollosas autoinmunes resistentes a la terapia convencional. Su mecanismo de acción, no bien conocido, supone un amplio espectro de inmunorregulación. En los últimos 5 años se han publicado varios trabajos en pacientes con pénfigo vulgar resistente con un beneficio clínico y serológico en el 80%-90% de los casos. Presentamos 3 casos de pénfigo vulgar con determinación seriada mediante la técnica de ELISA de anticuerpos antidesmogleína 1 y 3 (AcDsG1 y AcDsG3) durante un período de 8 meses en los que, a pesar de la mejoría clínica, no se objetivó disminución significativa en la concentración de anticuerpos. La terapia con IgIV, aun con beneficio clínico, no disminuyó en nuestros pacientes las cifras de anticuerpos y por ello debería quizá combinarse con inmunosupresores que inhiban la producción de anticuerpos patógenos

Intravenous immunoglobulin therapy (IVIg) has been used in the treatment of autoimmune bullous diseases unresponsive to conventional therapy in recent years. The action mechanism, which is not well known, suggests a wide spectrum of immunoregulation. In the last five years, several studies on patients with unresponsive pemphigus vulgaris with a clinical and serological outcome after IVIg administration in 80%-90% of cases have been published. We report the case of 3 patients with pemphigus vulgaris in whom we measured autoantibody titers to desmoglein 3 and 1 during 8 months. In spite of the clinical improvement, no significant decrease in antibody concentration was observed. Therapy with IVIg, although it has clinical benefit, did not decrease antibody values in our patients and thus it may need to be combined with immunosuppressant that inhibit pathogen antibody production

[Systemic autoimmune disease in patients with uveitis]. / Enfermedad autoinmune sistémica en pacientes con uveítis.

OBJECTIVE: A descriptive study was conducted on patients with uveitis to determine the frequency of associated autoimmune systemic diseases. METHODS: 64 patients with uveitis were studied. The patients were not known to have an underlying autoimmune systemic disease prior to the diagnosis of uveitis. All patients had the following immunological tests performed: serum immunoglobulins, complement components, circulating immune complexes (CIC), antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-cardiolipin antibodies (ACA) and major histocompatibilty complex antigens. RESULTS: A relationship with a sub-clinical autoimmune systemic disorder could be presumed in eleven cases (17.2%). This was defined by positive autoantibodies (ANA, ANCA or ACA) in the presence of complement consumption, hyper-gammaglobulinemia or increased CIC without clinical criteria of a defined autoimmune disease. A definite association with systemic autoimmune disease was defined in four patients (6.25%). The observed autoimmune systemic diseases were Sjögren's syndrome (n=2, 3.13%), anti-phospholipid syndrome associated with lupus-like disease (n=1, 1.6%), and systemic vasculitis (n=1, 1.6%). Lupus-like disease (n=4, 6.25%) was also observed. CONCLUSION: In a significant proportion of patients with uveitis an autoimmune systemic disorder may be present and should be looked for.

Enfermedad autoinmune sistémica en pacientes con uveítis / Systemic autoimmune disease in patients with uveitis

Objetivo: La realización de un estudio descriptivoen pacientes con uveítis para establecer la frecuenciade enfermedad autoimmune sistémica asociada.Métodos: Se incluyeron en el estudio 64 pacientescon uveítis. Ninguno de los pacientes estudiadostenia una enfermedad autoinmune sistémica conocidaantes del diagnóstico de uveítis. A todos lospacientes se les realizó un protocolo diagnósticoque incluyó las siguientes pruebas inmunológicas:inmunoglobulinas séricas, factores del complemento,inmunocomplejos circulantes (ICC), anticuerposantinucleares (ANA), anticuerpos anticitoplasma deneutrófilos (ANCA), anticuerpos anticardiolipina(ACA) y antígenos del complejo mayor de histocompatibilidad.Resultados: En once casos (17,2%) se objetivóasociación con un proceso autoinmune subclínicocaracterizado por la positividad de autoanticuerpos(ANA, ANCA o ACA) en presencia de consumo decomplemento, hipergammaglobulinemia o ICC elevados, sin que los pacientes cumpliesen criteriosclínicos de una enfermedad autoinmune. Se encontróuna asociación definitiva con enfermedadautoimmune sistémica en cuatro pacientes (6,25%).Las enfermedades autoinmunes observadas fueronel síndrome de Sjögren (n=2, 3,13%), síndromeantifosfolípido asociado a enfermedad lupus like(n=1, 1,6%) y vasculitis sistémica (n=1, 1,6%).También se observó un grupo de pacientes conenfermedad lupus like (n=4, 6,25%).Conclusión: En una proporción de pacientes conuveítis puede existir un proceso autoimmune sistémicosubyacente

Objective: A descriptive study was conducted on patients with uveitis to determine the frequency of associated autoimmune systemic diseases. Methods: 64 patients with uveitis were studied. The patients were not known to have an underlying autoimmune systemic disease prior to the diagnosis of uveitis. All patients had the following immunological tests performed: serum immunoglobulins, complement components, circulating immune complexes (CIC), antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), anticardiolipin antibodies (ACA) and major histocompatibilty complex antigens. Results: A relationship with a sub-clinical autoimmune systemic disorder could be presumed in eleven cases (17.2%). This was defined by positive autoantibodies (ANA, ANCA or ACA) in the presence of complement consumption, hyper-gammaglobulinemia or increased CIC without clinical criteria of a defined autoimmune disease. A definite association with systemic autoimmune disease was defined in four patients (6.25%). The observed autoimmune systemic diseases were Sjögren’s syndrome (n=2, 3.13%), anti-phospholipid syndrome associated with lupus-like disease (n=1, 1.6%), and systemic vasculitis (n=1, 1.6%). Lupus-like disease (n=4, 6.25%) was also observed. Conclusion: In a significant proportion of patients with uveitis an autoimmune systemic disorder may be present and should be looked for

Efficacy and safety of Etanercept, high-dose intravenous gammaglobulin and plasmapheresis combined therapy for lupus diffuse proliferative nephritis complicating pregnancy.

We report one case of pregnancy-onset severe diffuse proliferative nephritis in a patient with systemic lupus erythematosus (SLE), who was successfully treated with a combination of anti-tumour necrosis factor (TNF)-alpha, plasmapheresis and high-dose intravenous gammaglobulin. No flares were observed either in clinical symptoms or in laboratory examinations during pregnancy or after delivery. Her autoantibodies except fluorescent anti-nuclear antibodies were negative. We suggest that a combination of anti-TNF-alpha, plasmapheresis and high-dose intravenous gammaglobulin may be a safe and effective therapy for pregnant patients suffering severe lupus nephritis.

Discordance between anti-beta2-glycoprotein-I and anti-cardiolipin antibodies in patients with clinical criteria of antiphospholipid syndrome.

OBJECTIVES: Clinical and immunological features of patients with clinical manifestations of the antiphospholipid syndrome (APS) with anti-beta2-glycoprotein-I antibodies (anti-beta2-GP-I) but without anticardiolipin antibodies (aCL) or any other autoimmune condition are not well documented. We sought to determine the clinical significance of positive anti-beta2-GP-I with negative aCL. METHODS: From July 2002 through July 2003, 1,179 serum samples obtained in our hospital from the Community of Madrid were tested for anti-beta2-GP-I and aCL by enzyme-linked immunosorbent assay. Clinical records of patients with discordant anti-beta2-GP-I and aCL were retrospectively analysed. RESULTS: A total of 56 patients with discordant anti-beta2-GP-I and aCL were identified. By logistic regression analysis, after adjusting for age, sex and risk factors of thrombosis, the risk for developing APS criteria associated with anti-beta2-GP-I was significant [odds ratio 3.88; 95% confidence interval (CI): 1.05-14.27; p = 0.04). 15 out of 56 patients (26.8%) had positive anti-beta2-GP-I and negative aCL. 5 out of 15 anti-beta2-GP-I-positive patients had clinical APS without serological nor clinical evidence of any autoimmune disease. CONCLUSION: Determination of anti-beta2-GP-I should be considered in individual cases with clinical manifestations of primary APS and repeated negative results on conventional antiphospholipid antibody test.

Prevalence of IgG anti-{alpha}-fodrin antibodies in Sjogren's syndrome.

The objective of this study was to determine the prevalence of antibodies against alpha-fodrin (alpha-fodrin) of the immunoglobulin G (IgG) isotype in Sjögren's syndrome (SS), as defined by European Community Study Group (ESG) and ESG-modified criteria. We arrived at the prevalence and mean concentrations of IgG anti-alpha-fodrin antibodies using enzyme-linked immunosorbent assay (ELISA) in 507 patients with SS, primary SS (pSS), and secondary SS (sSS), classified according to either the ESG or the ESG-modified criteria. IgG anti-alpha-fodrin antibodies were detected in 6/507 (1.2%) and 4/228 (1.7%) of the SS group, according to the ESG or ESG-modified criteria, respectively. Similar prevalence was found for patients with pSS or sSS. Anti-Ro/SSA antibodies were present in 151/409 (36.9%) vs. 149/213 (70.0%) of the SS group, 85/195 (43.6%) vs. 83/101 (82.2%) of the pSS group, and 66/214 (30.8%) vs. 66/112 (58.9%) of the sSS group. Anti-La/SSB antibodies were detected in 77/403 (19.1%) vs. 73/212 (34.4%) of the SS group, 47/194 (24.2%) vs. 45/101 (44.5%) of the pSS group, and 30/209 (14.3%) vs. 28/111 (25.2%) of the sSS group. No clinical associations were found. Only two IgG anti-alpha-fodrin-positive sera were anti-Ro/SSA-negative. We conclude that IgG antibodies against alpha-fodrin are present in a small percentage of people with SS, pSS, and sSS. The lower prevalence in patients classified according to the ESG criteria reflects the lower specificity of these criteria. IgG anti-alpha-fodrin antibodies can be detected in some SS patients whose sera do not contain anti-Ro/SSA antibodies.

[Autoimmune disease in primary antibody deficiencies]. / Enfermedad autoinmune en inmunodeficiencias primarias de anticuerpos.

BACKGROUND: Immunodeficiency and autoimmune phenomena may occur concomitantly in the same individual. Many immune deficiency syndromes, mainly humoral defects, are associated with autoimmune disorders. In the present study, we describe the frequency of autoimmune disorders in these patients. METHODS AND RESULTS: We performed a retrospective review of the medical records of a cohort of 152 patients with primary antibody deficiency in the Clinical Immunology Unit of the Gregorio Maranon University Hospital in Madrid: common variable immunodeficiency (CVID) (n = 35), IgA deficiency (n = 43), specific IgG subclass deficiency (n = 56), antibody deficiency with normal immunoglobulin (n = 14) and X-linked agammaglobulinemia (n = 4). Of the 152 patients with primary antibody deficiencies, autoimmune disorders were found in 35 (23 %). Autoimmune hematologic disease was found in 14 patients (9.2 %), autoimmune diseases of the gastrointestinal tract in eight (5.3 %), autoimmune endocrine diseases in six (3.9 %), autoimmune rheumatic diseases in six (3.9 %) and vitiligo in four. Autoimmune diseases were more frequent in CVID patients (37.1 %) than in those with selective IgA deficiency (25.5 %) or selective IgG subclass deficiency (12.5 %). Thirty-seven percent of autoimmune episodes occurred prior to the diagnosis of primary antibody deficiency. Sixteen patients (10.5 %) had autoantibodies without clinical data of an autoimmune disease. CONCLUSIONS: Primary antibody deficiencies have variable autoimmune manifestations. For early detection and appropriate treatment, autoimmune disease should be suspected in patients with immunodeficiency.

Enfermedad autoinmune en inmunodeficiencias primarias de anticuerpos / Autoimmune disease in primary antibody deficiencies

Fundamento: Inmunodeficiencia y autoinmunidad pueden coexistir en el mismo individuo. Muchas enfermedades de inmunodeficiencia, principalmente aquellas en las que predomina una deficiencia de anticuerpos, asocian procesos autoinmunes. Describimos la prevalencia de enfermedad autoimmune en estos pacientes. Métodos y resultados: Estudio retrospectivo de revisión de historias clínicas de una cohorte de 152 pacientes con deficiencia primaria de anticuerpos atendidos en la Unidad de Inmunología Clínica del Hospital Gregorio Marañón en Madrid: inmunodeficiencia variable común (IDVC) (n = 35), deficiencia de IgA (n = 43), deficiencia específica de subclases de IgG (n = 56), deficiencia de formación de anticuerpos con inmunoglobulinas normales (n = 14) y agammaglobulinemia ligada al sexo (n = 4). De los 152 pacientes 35 tuvieron enfermedades autoinmunes (23%). Catorce pacientes padecían citopenias autoinmunes (9,2%), 8 enfermedad autoinmune del aparato digestivo (5,3 %), 6 enfermedad autoinmune endocrina (3,9%), 6 conectivopatías autoinmunes (3,9%) y otros 4 vitíligo. La presencia de enfermedad autoinmune fue más frecuente en la IDVC (37,1%) que en la deficiencia de IgA (25,5%) o que en la deficiencia de subclases de IgG (12,5%). El 37% de los episodios autoinmunes ocurrieron antes del diagnóstico de la inmunodeficiencia. En 16 pacientes (10,5%) se detectaron autoanticuerpos sin datos clínicos de actividad de un proceso autoinmune. Conclusiones: Los pacientes con deficiencia primaria de anticuerpos pueden tener procesos autoinmunes de diverso tipo. El diagnóstico de proceso autoimmune debe sospecharse para su detección precoz y tratamiento apropiado en pacientes con inmunodeficiencia

Background: Immunodeficiency and autoimmune phenomena may occur concomitantly in the same individual. Many immune deficiency syndromes, mainly humoral defects, are associated with autoimmune disorders. In the present study, we describe the frequency of autoimmune disorders in these patients. Methods and results: We performed a retrospective review of the medical records of a cohort of 152 patients with primary antibody deficiency in the Clinical Immunology Unit of the Gregorio Marañon University Hospital in Madrid: common variable immunodeficiency (CVID) (n = 35), IgA deficiency (n = 43), specific IgG subclass deficiency (n = 56), antibody deficiency with normal immunoglobulin (n = 14) and X-linked agammaglobulinemia (n = 4). Of the 152 patients with primary antibody deficiencies, autoimmune disorders were found in 35 (23%). Autoimmune hematologic disease was found in 14 patients (9.2%), autoimmune diseases of the gastrointestinal tract in eight (5.3%), autoimmune endocrine diseases in six (3.9%), autoimmune rheumatic diseases in six (3.9%) and vitiligo in four. Autoimmune diseases were more frequent in CVID patients (37.1%) than in those with selective IgA deficiency (25.5%) or selective IgG subclass deficiency (12.5%). Thirty-seven percent of autoimmune episodes occurred prior to the diagnosis of primary antibody deficiency. Sixteen patients (10.5%) had autoantibodies without clinical data of an autoimmune disease. Conclusions: Primary antibody deficiencies have variable autoimmune manifestations. For early detection and appropriate treatment, autoimmune disease should be suspected in patients with immunodeficiency

Simultaneous identification of various antinuclear antibodies using an automated multiparameter line immunoassay system.

The objective was to determine the sensitivity and specificity of an automated multiparameter line immunoassay system compared with other techniques for the identification of autoantibodies in rheumatic diseases. We studied sera from 90 patients. Anti-U1RNP, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti-Jo 1 and anti-Scl 70 antibodies were identified by counterimmunoelectrophoresis (CIE) techniques, enzyme-linked immunosorbent assay (ELISA), immunoblotting (IB) using extracts of rabbit thymus and human placenta, and an automated multiparameter line immunoassay system (INNO-LIA ANA UPDATE K-1090) that detects nine different antibodies simultaneously (anti-U1RNP, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti-Scl 70, anti-Jo 1, anticentromere, antihistone, and antiribosomal P protein). The line immunoassay system equaled or surpassed the other techniques in the identification of anti-Sm, anti-La/SS-B, anti-Jo 1 and anti-Scl 70 antibodies (sensitivity 100%, specificity 94-100%) and was similarly effective in the case of anti-U1RNP (sensitivity 87.5%, specificity 93.9%) and anti-Ro/SS-A (sensitivity 91.4%, specificity 87.2%) antibodies. In addition, this technique detected more 52 and 60 kD anti-Ro/SS-A sera than IB. Nine antibodies can be detected with this method at a cost of 25.38 Euros per serum sample. In five hours, 19 sera can be studied. The approximate cost of detecting these nine antibodies with an automated ELISA system would be 28.93 Euros, which allows 10 sera to be studied in four hours. In conclusion, the automated multiparameter line immunoassay system is a valid method for the detection of autoantibodies in rheumatic diseases. Its most notable advantages are automated simultaneous detection of several autoantibodies in the same serum and its lower cost compared with ELISA techniques.

Antiphospholipid antibodies: a risk factor for occlusive retinal vascular disorders. Comparison with ocular inflammatory diseases.

OBJECTIVE: To evaluate the prevalence of antiphospholipid antibodies (aPL) together with immunological characteristics of patients with occlusive retinal vascular disorders (ORVD) with and without risk factors (systemic arterial hypertension, diabetes mellitus, hyperlipidemia, and embolizing cardiac disease) for retinal occlusions compared to patients with ocular inflammatory diseases (OID) and healthy controls. METHODS: Sixty-eight patients with ORVD, 45 patients with OID, and 49 healthy persons were prospectively studied. Serologic studies included determination of anticardiolipin antibodies, lupus anticoagulant, antinuclear antibodies (ANA), levels of complement 4 and 3, total hemolytic complement (CH100), and circulating immune complexes (CIC). RESULTS: Elevated levels of aPL were detected in 16 (24%) patients with ORVD compared to 4 (9%) patients with OID (OR 3.15, p < 0.05) and 4 (8%) controls (OR 3.46, p < 0.05). No significant differences were seen in the prevalence of aPL comparing risk factor-positive patients with ORVD (8 of 33, 24%) to risk factor-free patients with ORVD (8 of 35, 23%). A higher frequency of positive ANA, elevated IgA, and increased CIC were detected in aPL positive patients with ORVD compared to patients with OID. CONCLUSION: Detection of aPL in patients with ORVD may help determine which patients are eligible for prophylactic treatment. An immunologic profile characterized by high prevalence of ANA, CIC, and elevated IgA distinguishes ORVD patients with aPL from inflammatory ophthalmologic disorders.

Frequency and significance of anti-Ro (SS-A) antibodies in multiple sclerosis patients.

OBJECTIVE: To determine the frequency and significance of antinuclear (ANA), anticardiolipin (ACA) and anti-Ro (SS-A) antibodies in multiple sclerosis (MS) patients. METHODS: ANA (indirect immunofluorescence), ACA and anti-Ro (SS-A) antibodies (ELISA) were tested in sera of 42 patients with Poser defined MS and 50 healthy individuals. RESULTS: High levels of anti-Ro (SS-A) antibodies were found in 3 patients (7%) (vs 0 in the control group). Two of them had normal salivary gland biopsy. Clinical MS form was chronic-progressive in 2 cases and relapsing-remitting in the third one. Ten patients (23%) had low levels of ANA (vs 4%), none of them positive for anti-Ro (SS-A) antibodies. Only 1 patient (2%) with RR clinical form had ACA (vs 0). No clinical or neuroradiological differences with conventional MS patients were observed. CONCLUSIONS: ANA, ACA and anti-Ro (SS-A) antibodies in MS patients indicate an underlying autoimmune disease but our series suggests that they are an epiphenomenon of a more diffuse immunological dysfunction.

Estudio de concordancia entre anticuerpos IgA antitransglutaminasa tisular recombinante humana y anticuerpos IgA antiendomisio / Study of the agreement between Iga human recombinant tissular transglutaminase antibodies and IgA endomysial antibodies

Introducción: La enfermedad celíaca (EC) o enteropatía sensible al gluten es un trastorno intestinal de, etiología multifactorial. En su patogenia se encuentran implicados ge-nes HLA y no-HLA, el gluten dietético (trigo, avena, cebada y centeno) y posiblemente factores medioambientales adicionales. La EC se caracteriza por la presencia de atrofia vellositaria en el intestino delgado, demos-trada mediante biopsia. La prevalencia es del 0,1 por ciento. Suele producir sintomatología clí-nica entre el segundo y el tercer año de vida. La clínica clásica incluye diarrea crónica, distensión abdominal y escaso desarrollo pondostatural, sin embargo, puede aparecer mas tardíamente con una clínica más larvada, como anemia, fatiga, pérdida de peso, diarrea, estreñimiento e incluso sintomatología neurológica. El tratamiento consiste en la exclusión del gluten de la dieta. La persistencia de la exposición al gluten dietético se asocia con un riesgo elevado de anemia, infertilidad, osteoporosis y linfoma intestinal, así como aumento de la mortalidad.Para el diagnóstico de EC se utilizaron los criterios de la Sociedad Europea de Gastroenterología y Nutrición (ESPGAN). El estudio de diversos anticuerpos es de gran ayuda para el diagnóstico y seguimiento de la EC: a) los anticuerpos antigliadina de clase IgA (AGA-IgA) detectados mediante técnica ELISA presentan una sensibilidad (S) del 85 por ciento y una especifidad (E) del 82 por ciento y los de clase IgG (AGA IgG) presentan una S del 69 por ciento, y una E del 73 por ciento, y b) los anticuerpos antiendomisio de clase lg A (EMA-IgA) medidos mediante técnica de inmunofluorescencia indirecta (IIF) presentan una S del 93 por ciento y una E del 99 por ciento; y antirreticulina de tipo IgA (ARA-IgA), presentan una S del 92 por ciento y una E del 97 por ciento. Recientemente, Dieterich et al, utilizando un método de inmunoprecipitación, descubrieron un anticuerpo frente a la transglutaminasa tisular (TGt) de cobaya de tipo IgA (anti-TGt-IgA), presente en los pacientes con EC, con una S del 95 por ciento y una E del 94 por ciento. En este estudio hemos testado un nuevo anticuerpo frente a TGt recombinante humana de clase IgA (anti T GtR-IgA), medido mediante técnica de ELISA, y lo hemos comparado con la detección de anti-TGt-IgA (método utilizado actualmente) y con la detección de EMA-IgA (técnica de referencia).Materiales y métodos: Se estudiaron 133 sueros de pacientes con sospecha clínica de EC, utilizándose técnicas de IFI para detectar EMA-IgA y de ELISA para medir anti-TGt-IgA, poniéndose en marcha una nueva técnica de ELISA que detecta anti-TGtR-IgA. Resultados: Primero se compararon los anticuerpos anti-TGt-IgA en uso, respecto a los EMA-IgA, y se observó una S del 96,2010 y una E del 91,5 por ciento; valor predictivo positivo (VPP) del 74,2 por ciento y valor predictivo negativo (VPN) del 98,9 por ciento (X2= 85,56; p 4,001; alfa <0,001). Posteriormente se analizaron los mismos sueros comparando la positividad para anti-TGtR-IgA respecto a anti-TGt-IgA. Estos datos arrojan a su vez los siguientes valores: S= 74,2 por ciento; E= 98,9 por ciento; VPP= 96,2 por ciento; VPN= 91,5 por ciento (X2= 85,56; p 4,001; alfa <0,001). Por último, se comparó la positividad para anti-TGtR-IgA: respecto a EMA IgA, y se encontró una concordancia total entre ambas determinaciones: S= 100 por ciento; E= 100 por ciento; VPP= 100 por ciento; VPN= 100'0 (x2= 133; p 4,001; alfa 4,001).Conclusiones: La detección de anticuer-pos anti-TGtR-IgA presenta una sensibilidad y especifidad superiores a la detección de anti-TGt-IgA. Hemos observado una identidad total entre anti-TGtR-IgA y EMA-IgA, por tanto, la detección de anti-TGtR-IgA constituye una técnica sensible y específica que podría sustituir a la detección mediante IFI de EMA-IgA en el diagnóstico de EC. Como la detección de anti-TGtR-IgA tiene las ventajas de ser un ensayo cuantitativo, de rápida realización, no sometido a la varia-bilidad del observador y fácilmente reproducible, podría ser una herramienta muy útil en el diagnóstico y seguimiento de la EC (AU)

Analysis of the human neonatal thymus: evidence for a transient thymic involution.

The neonatal period is marked by the impairment of the major components of both innate and adaptive immunity. We report a severe depletion of cortical CD4+CD8+ double-positive thymocytes in the human neonatal thymus. This drastic reduction in immature double-positive cells, largely provoked by an increased rate of cell death, could be observed as early as 1 day after birth, delaying the recovery of the normal proportion of this thymocyte subset until the end of the first month of postnatal life. Serum cortisol levels were not increased in newborn donors, indicating that the neonatal thymic involution is a physiological rather than a stress-associated pathological event occurring in the perinatal period. Newborn thymuses also showed increased proportions of both primitive CD34+CD1- precursor cells and mature TCRalphabetahighCD69-CD1-CD45RO+/RAdull and CD45ROdull/RA+ cells, which presumably correspond to recirculating T lymphocytes into the thymus. A notable reinforcement of the subcapsular epithelial cell layer as well as an increase in the intralobular extracellular matrix network accompanied modifications in the thymocyte population. Additionally neonatal thymic dendritic cells were found to be more effective than dendritic cells isolated from children's thymuses at stimulating proliferative responses in allogeneic T cells. All these findings can account for several alterations affecting the peripheral pool of T lymphocytes in the perinatal period.

Antiphospholipid antibodies and retinal thrombosis in patients without risk factors: a prospective case-control study.

PURPOSE: To determine the prevalence of antiphospholipid antibodies and other immunologic abnormalities in patients with occlusive retinal vascular events, exempt from conventional risk factors of retinal thrombosis. METHODS: Forty patients with retinal vascular occlusion (26 with retinal vein occlusions, eight with arterial occlusions, two with combined venous and arterial occlusions, and four with venous occlusions plus vasculitis), free of main accepted risk factors for retinal thrombosis, were prospectively screened for antiphospholipid antibodies (anticardiolipin-antibodies and lupus anticoagulant) and other immunologic abnormalities. Fourteen patients were younger than 50 years. Prevalence and mean values of antiphospholipid antibodies (aPL) were compared with those in a homogeneous control group of 40 patients. RESULTS: The prevalence of antiphospholipid antibodies in the study group was 22.5% (nine of 40). Comparison with control group prevalence (5% [two of 40]) showed a statistically significant difference (P = .04). Six patients in the study group disclosed positivity for IgG-anticardiolipin antibodies, one patient for IgM anticardiolipin antibodies, and two patients for both isotypes IgG and IgM anticardiolipin antibodies. The antibody assay for lupus anticoagulant was negative for all patients. Three patients were diagnosed as having primary antiphospholipid antibody syndrome and are undergoing systemic anticoagulant therapy. Relevant immunologic abnormalities were also found (27.5% with antinuclear antibodies, 35% with elevation of circulating immune complexes, 35% with complement deficiency, 30% with positive rheumatoid factor, and 17.5% with positive C-reactive protein). Thirteen patients (32.5%) had more than four parameters altered. No significant association was found between prevalence or mean values of anticardiolipin antibody and patients younger than 50 years. CONCLUSIONS: The high prevalence of anticardiolipin antibodies in patients with vaso-occlusive retinopathy exempt from conventional risk factors, and the relevant diagnostic and therapeutic implications, lead us to recommend a systematic search for specific antiphospholipid antibodies in such patients.

Immunological abnormalities in primary APS evolving into SLE: 6 years follow-up in women with repeated pregnancy loss.

We have performed a prospective study to determine the prevalence of immunological abnormalities and the evolution from primary antiphospholipid syndrome (APS) into systemic lupus erythematosus (SLE) in women who had had unexplained repeated pregnancy loss (PL) and APS. Of 105 women with abortions or fetal deaths, 33(31%) fulfilled criteria for APS. Among these patients with primary APS, 24% had antinuclear antibodies (ANA), 91% had elevated circulating immune complexes (CIC), 70% had low total haemolytic complement (CH100), 52% had low levels of complement 4 (C4) and 30% had low levels of complement 3 (C3), in a significantly higher prevalence than women whose pregnancies were successful (control group). Through out a 6 y follow-up, 3 (9%) of the patients with APS who had autoimmune related abnormalities when entered into the study developed features of lupus like disease (LLD) or fullblown SLE. Our findings suggest that women with unexplained repeated PL with APS who presented with positive ANA, high levels of CIC, low levels of CH100, C3 and C4, may define a subset of patients exhibiting immunological alterations similar to those of SLE. These parameters may help in the assessment of prognosis in APS patients with PL. Those patients should be carefully surveyed with regard to the development of connective tissue diseases.

Immunological and clinical differences between juvenile and adult onset of systemic lupus erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) in children usually follows a more severe course than in adults, but sometimes in the previous studies reported there are many confounding factors. OBJECTIVE: To analyse the immunological and clinical characteristics of SLE juvenile onset and SLE adult onset. METHODS: We studied 179 patients with SLE, 49 patients were aged 6-18 yrs at onset of disease. Anti-dsDNA antibodies were detected by radioimmunoassay and antibodies to extractable nuclear antigens (ENA): anti-nRNP, anti-Sm, anti-Ro/SS-A and anti-La/SS-B antibodies by ELISA, counterimmuno-electrophoresis and immunoblotting. RESULTS: Juvenile-onset SLE shows a higher frequency of cutaneous vasculitis (44.8% vs 27.6%; P < 0.05), seizures (18.3% vs 7.6%; P < 0.05) nephropathy (67.3% vs 48.4%; P < 0.025), and discoid lupus erythematosus (26.5% vs 13.8%; P < 0.05). The incidence of articular manifestations is lower than in adults (85.7% vs 96.1%; P < 0.025). No significant differences were found between the two groups in relation with the prevalence of antinuclear antibodies. CONCLUSIONS: Juvenile-onset SLE has more frequent neurological and renal manifestations than adult-onset SLE, but immunological markers are similar in both groups. These features suggest the most severe clinical manifestations in the juvenile-onset SLE group are not related with the presence of studied antibodies by different methods.

[Giant cell arteritis, bilateral anterior ischemic optic neuropathy and anticardiolipin antibodies]. / Arteritis de células gigantes, neuropatía óptica isquémica anterior bilateral y anticuerpos anticardiolipina.

CLINICAL CASE: We report a case of giant cell arteritis (GCA) that developed acute bilateral amaurosis secondary to anterior ischemic optic neuropathy (AION), without other symptoms and with a normal erythrocyte sedimentation rate (ESR). Physical examination revealed painless and pulseless temporal arteries, ophthalmoscopic findings were blurring of margins, hyperaemia and elevation of both optic discs. Visual acuity was limited to hand motion perception and light-darkness discrimination. Six months before of this syndrome, the patient was diagnosed of polymyalgia rheumatica and was maintained asymptomatic with 6 mg/day of deflazacort. Temporal artery biopsy was diagnostic. An elevated IgG type anticardiolipin antibodies (ACA) rate was detected in serum. The remaining laboratory studies were normal. CONCLUSIONS: In old people with uni or bilateral acute visual loss, even with normal erythrocyte sedimentation rate and without other symptoms associated, it is necessary to have a high index of suspicion in order to detect giant cell arteritis. This can facilitate an early diagnosis and immediate initiation of treatment with high doses of corticosteroids. An elevated level of IgG type anticardiolipin antibodies may be a risk factor to thrombotic complications, as anterior ischemic optic neuropathy, in patients with giant cell arteritis.

Anti-BB'-Sm antibodies, anticardiolipin antibodies, and thrombosis in systemic lupus erythematosus.

OBJECTIVE: Anticardiolipin antibodies (aCL) are associated with thrombosis in patients with systemic lupus erythematosus (SLE). Our aim was to determine whether there is an association between aCL, anti-Sm antibodies, and thrombosis in patients with SLE. METHODS: Sera from 153 patients with SLE were studied by ELISA, immunoblotting, and counter-immunoelectrophoresis (CIE) for anti-Sm antibodies, aCL and anti-dsDNA antibodies were detected by ELISA and radioimmunoassay, respectively. RESULTS: Anti-Sm antibodies were detected in 62 patients (40.5%) by ELISA and in 16 (10.4%) by CIE; IgG-anti-BB'-Sm in 44 (28.7%) by immunoblotting; IgG-aCL in 82 (53.5%), IgM-aCL in 44 (28.7%), and anti-dsDNA antibodies in 128 (83.6%). Anti-Sm and anti-dsDNA antibodies were significantly more frequent in patients with than in patients without aCL. Of the 89 patients with aCL, 36 (40.4%) showed IgG-anti-BB'-Sm antibodies (OR: 4.7; 95% CI: 2-10.5). Thrombosis was present in 20 (22.4%) SLE patients with aCL and in two (3.1 %) SLE patients without aCL (OR: 8.9; 95% CI: 2.4-31.8). Of the 22 patients with thrombosis, five (22.7%) had precipitating anti-Sm antibodies (OR: 3.2; 95% CI: 1.04-9.8) and 14 (63.6%) showed IgG-anti-BB'-Sm antibodies (OR: 5.8; 95% CI: 2.3-14). Anti-BB'-Sm and aCL were significantly more frequent in patients with anti-dsDNA antibodies (32 and 62%) than in patients without these antibodies (12 and 36%) (OR: 3.4 and 2.9; 95% CI: 1.03-11.1 and 1.2-6.7, respectively). CONCLUSION: IgG-anti-BB'-Sm antibodies are associated with aCL, anti-dsDNA, and thrombosis in patients with SLE. Our findings suggest a possible association between anti-Sm, anti-dsDNA, and aCL responses in these patients.

Antiribonucleoprotein antibodies in children with HIV infection: a comparative study with childhood-onset systemic lupus erythematosus.

A number of clinical and laboratory features of HIV infection are found in systemic lupus erythematosus (SLE). The objective of this study was to analyze the presence of circulating antibodies to small nuclear ribonucleoproteins (snRNP) in both diseases. Sera from 44 HIV-infected children, from 22 patients with childhood-onset SLE, and from 50 healthy children were studied. Anti-snRNP antibodies were detected by ELISA using recombinant and affinity-purified nuclear antigens, by counterimmunoelectrophoresis (CIE), and by immunoblotting using extractable nuclear antigens. Results included the detection of anti-snRNP antibodies by ELISA in 30 HIV-infected patients (68.1%) and 19 SLE patients (86.3%). These antibodies were directed against U1-RNP (61.3% and 77.2%, respectively), Sm (29.5% and 54.5%, respectively), 60 kDa Ro/SS-A (47.7% and 50%, respectively), and La/SS-B proteins (18.1% and 9%, respectively). None of the HIV-infected children and 11 SLE patients (50%) showed anti-snRNP antibodies by CIE. None of the HIV-infected patients showed anti-70 kDa U1-RNP or anti-D-Sm antibodies by immunoblotting. No differences between the two groups were noted on the presence of nonprecipitating anti-snRNP antibodies. No such reactivities were observed among the normal sera tested. The authors concluded that nonprecipitating anti-snRNP antibodies in HIV-infected children are as frequent as in childhood-onset SLE. The significance of these antibodies is not clear at present. Although polyreactive and low-affinity antibodies and a mechanism of molecular mimicry may explain these results, a specific stimulation of B cells by nuclear antigens could not be excluded.