IL28RA polymorphism (rs10903035) is associated with insulin resistance in HIV/HCV-coinfected patients.

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), although mechanisms leading to IR in these patients are not completely understood. The aim of this study was to evaluate the association of interleukin 28B (IL28B) and interleukin 28 receptor alpha (IL28RA) polymorphisms with IR among human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out a cross-sectional study on 203 patients. IL28B (rs8099917) and IL28RA (rs10903035) polymorphisms were genotyped by GoldenGate(®) assay. IR was defined as homeostatic model assessment (HOMA) values ≥3.00. Univariate and multivariate generalized linear models (GLM) were used to compare HOMA values and the percentage of patients with IR according to IL28B and IL28RA genotypes. In total, 32% (n = 65/203) of the patients had IR. IL28B rs8099917 TT was not significantly associated with HOMA values and IR. In contrast, rs10903035 AA was significantly associated with high HOMA values taking into account all patients (P = 0.024), as well as the subgroups of patients with significant fibrosis (P = 0.047) and infected with HCV genotype 3 (P = 0.024). Additionally, rs10903035 AA was significantly associated with IR (HOMA ≥3.00) in all patients (adjusted odds ratio (aOR) = 2.02; P = 0.034), in patients with significant fibrosis (aOR = 2.86; P = 0.039) and HCV genotype 3 patients (aOR = 4.89; P = 0.031). In conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype.

Association of torque teno virus (TTV) and torque teno mini virus (TTMV) with liver disease among patients coinfected with human immunodeficiency virus and hepatitis C virus.

Torque teno virus (TTV) and torque teno mini virus (TTMV) have been potentially related to liver diseases. The aim of the study was to quantify TTV and TTMV in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients to study the relationship between the TTV and TTMV viral loads and the severity of liver disease. We carried out a cross-sectional study in 245 patients coinfected with HIV and HCV (HIV/HCV-group), 114 patients monoinfected with HIV (HIV-group), and 100 healthy blood donors (Control-group). Plasma samples were tested for TTV and TTMV by quantitative real-time polymerase chain reaction (PCR). The prevalences of TTV and TTMV infections in the HIV/HCV-group and the HIV-group were significantly higher than the Control-group (p < 0.05). Furthermore, TTV and TTMV coinfections were found in 92.2 % (226/245) in the HIV/HCV-group, 84.2 % (96/114) in the HIV-group, and 63 % (63/100 %) in the Control-group (p ≤ 0.05). HIV/HCV-coinfected patients with HIV viral load ≥50 copies/mL and patients with severe activity grade had the highest viral loads of TTV and TTMV (p ≤ 0.05). HIV/HCV-coinfected patients with high TTV load (>2.78 log copies/µL) had increased odds of having advanced fibrosis or severe necroinflammatory activity grade in the liver biopsy. Moreover, HIV/HCV-coinfected patients with high TTMV load (>1.88 log copies/µL) had decreased odds of having no/minimal fibrosis and no/mild activity grade, and increased odds of having a high fibrosis progression rate. In conclusion, TTV and TTMV might play a role in the development of liver disease in immunodeficiency patients, such as the patients coinfected with HIV and HCV.

Adipokine profiles and lipodystrophy in HIV-infected children during the first 4 years on highly active antiretroviral therapy.

OBJECTIVE: The aim of the study was to evaluate the evolution of plasma adipokines and lipodystrophy in protease inhibitor-naive vertically HIV-infected children on highly active antiretroviral therapy(HAART). PATIENTS AND METHODS: We carried out a multicentre retrospective study of 27 children during 48 months on HAART. Every 3 months, CD4+ T-cells, CD8+ T-cells, viral load (VL), cholesterol, triglycerides, lipoproteins and adipokines were measured. Diagnoses of lipodystrophy were based on clinical examinations. RESULTS: We found hypercholesterolaemia (4200 mg/dL) in 9.5, 30.4, 21.7, 14.3 and 13.3% of the subjects at months 0, 12, 24, 36 and 48, respectively, and hypertriglyceridaemia (4170 mg/dL) in 14.3, 8.3, 13,4.5 and 0% at the same time-points. During follow-up, and especially at the end of the study, we found an increase in plasma resistin levels and significant increases in total plasminogen activator inhibitor type 1, adiponectin, and leptin levels (Po0.05). We also observed slight increases in the leptin/adiponectin ratio, homeostatic model assessment, and C-peptide values during the first months of treatment followed by a moderate decrease or stabilization after 24 months on HAART.At the end of the study, 12 of the 27 children (44.4%) had lipodystrophy, 10 (37%) had lipoatrophy,and 11 (40.7%) had lipohypertrophy; and only three of the 27 children (11.1%) were diagnosed with lipoatrophy and lipohypertrophy with scores 2. CONCLUSIONS: HIV-infected children showed an increase in serum adipokine levels, but this was not associated with the emergence of lipodystrophy during 48 months on HAART.

Soluble Fas and Fas ligand in HIV/HCV coinfected patients and impact of HCV therapy.

The aim of this study was to evaluate the influence of clinical and epidemiological characteristics of 183 HIV/HCV coinfected patients and HCV clearance after antiviral treatment on serum sFas and sFasL levels. Thirty out of 183 patients underwent HCV antiviral therapy with IFN-α + RBV for a duration of 48 weeks. HCV genotype 1 and homeostasis model assessment for insulin resistance (HOMA-IR) had a significant positive relationship, and CD4+/µL had a significant negative relationship with sFas (R-square = 0.582; p < 0.001) and sFasL (R-square = 0.216; p < 0.001) in multivariate linear regression analysis. HCV genotype 1 was the only significant variable associated with the sFas/sFasL ratio (R-square = 0.201; p < 0.001). sFas and sFasL levels had positive significant correlations with serum sICAM-1, sVCAM-1, and HOMA levels (p < 0.05). Among patients on IFN-α + RBV therapy, 15 patients showed a sustained virologic response (SVR), while 15 patients were non-responders (NR). Patients with SVR had significant decreases in sFas (p = 0.008) and sFas/sFasL ratio (p = 0.002), while non-responders had a significant increase in sFasL values (p = 0.013). In conclusion, HCV genotype 1, high HOMA, and low CD4+/µL were associated with high serum levels of sFas and sFasL, which indicate higher levels of inflammation and, possibly, increased cardiovascular risk. Moreover, response to HCV antiviral therapy is known to reduce inflammation.

CD81 expression in peripheral blood lymphocytes before and after treatment with interferon and ribavirin in HIV/HCV coinfected patients.

BACKGROUND: CD81 is expressed on lymphocytes and confers HCV viral infectivity support. The aim of our study was to quantify CD81 expression in peripheral blood B- and T-cells of HCV/HIV-coinfected patients and healthy subjects to examine its association with several HCV virological characteristics and the therapeutic responsiveness to HCV antiviral treatment. METHODS: We carried out a cross-sectional study on 122 naïve patients. For a duration of 48 weeks, 24 out of 122 patients underwent HCV antiviral therapy with interferon (IFN)-alpha and ribavirin. T- and B-cell subsets were analysed by flow cytometry. RESULTS: We found that HIV/HCV coinfected patients with HCV-RNA > or =850 000 IU/mL had lower values of %CD19+CD81-CD62L+ and %CD19+CD62L+; and higher values of CD19+CD81+CD62L- and CD19+CD81+ percentages and absolute counts than patients with HCV-RNA <850 000 IU/mL. Similarly, HIV/HCV coinfected patients with the genotype 1 had lower values of %CD19+CD81-CD62L+ and higher values of CD3+CD81+CD62L- and CD3+CD81+ percentages and absolute counts than patients without genotype 1. Moreover, we found that HIV/HCV coinfected patients had higher values of %CD19+HLA-DR+CD25+, %CD19+CD40+CD25+ and %CD19+CD25+ than healthy control patients. When we studied the B- and T-cell subset kinetics of 24 HIV/HCV coinfected patients on HCV antiviral therapy, we found a significant decrease in CD3+CD81+and CD3+CD81+CD62L- subsets and a significant increase in CD3+CD62L+ and CD3+CD81+CD62L+ percentages and absolute counts, but the variation in these markers disappeared several months after stopping the treatment. CONCLUSIONS: We observed a different pattern of CD81 T-cell and B-cell levels in naïve HIV/HCV coinfected patients according to HCV virological status and their subsequent variations during HCV antiviral treatment. CD81 expression might influence HCV pathogenesis and response to HCV antiviral treatment.

Diagnosis of advanced fibrosis in HIV and hepatitis C virus-coinfected patients via a new noninvasive index: the HGM-3 index.

BACKGROUND: Noninvasive tests are increasingly being used for the assessment of liver fibrosis. We aimed to develop a serum index for the identification of advanced fibrosis (F>or=3) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: We carried out a cross-sectional study on a group of 195 patients comprised of an estimation group (EG; n=127) and a validation group (VG; n=68) who all underwent liver biopsy and had not received previous interferon therapy. Liver fibrosis was estimated using the METAVIR score. We developed a new serum index (HGM-3) dependent on levels of platelets, alkaline phosphatase, hepatic growth factor, tissue inhibitor of metalloproteinase-1 and hyaluronic acid. RESULTS: In the EG, the area under the receiver operating characteristic curve (AUC-ROC) of HGM-3 for identification of F>or=3 was 0.939 [95% confidence interval (CI) 0.899, 0.979] which was significantly higher than the AUC-ROC of the HGM-2, FIB-4, aspartate aminotransferase to platelet ratio (APRI) and Forns' indexes. With HGM-3 <0.135 for F<3, 57 patients were correctly identified and two patients were misclassified. We found the presence of F<3 with 96.6% certainty. The negative likelihood ratio (LR) was <0.1 and the diagnostic odds ratio (DOR) was >40. With HGM-3 >0.570 in the EG for F>or=3, 31 patients were correctly identified, and five patients were misclassified. We found the presence of F>or=3 with 86.1% certainty. The positive LR was >12 and the DOR was >40. For the VG, the diagnostic accuracy values were similar to the values for the EG. CONCLUSIONS: HGM-3 appears to be an accurate noninvasive method for the diagnosis of bridging fibrosis and cirrhosis in HIV/HCV-coinfected patients.

Serum levels of fibrosis biomarkers measured early after liver transplantation are associated with severe hepatitis C virus recurrence.

This prospective study analyzed the relationship between several biological markers related to liver fibrosis at 3 months and 1 year post liver transplantation in 37 patients (19 with hepatitis C virus [HCV], 18 with alcoholic liver disease). Severe HCV recurrence (HCV-SR) was defined as fibrosis stage > or =F1 (METAVIR score) at 1 year and/or a value of hepatic venous pressure gradient > or=6 mmHg. We found HCV-SR patients had higher values of monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and hyaluronic acid (HA) than non-severe HCV recurrence patients (P<0.05). Moreover, receiver operating characteristic curve analysis showed that interferon-inducible protein 10 (IP-10) (area under the curve [AUC]: 0.74; confidence interval [CI] 95%: 0.49-0.91; P=0.043), MCP-1 (AUC: 0.78; CI 95%: 0.54-0.94; P=0.007), sVCAM-1 (AUC: 0.89; CI 95%: 0.67-0.98; P=0.005), and HA (AUC: 0.80; CI 95%: 0.55-0.94; P=0.035) have good predictive capacity for identifying severe HCV infection. The evaluation of these biomarkers may be useful in the early identification of patients in whom a more aggressive therapeutic approach could be necessary.

High rate of infection and immune disorders in patients with hepatitis C virus after liver transplantation.

The aim of this prospective study was to analyze the incidence of serious infections and changes in immunological markers after liver transplantation (LT) in a cohort of patients with hepatitis C virus (HCV). This study included 34 patients who had LT, 20 patients with HCV etiology (HCV group), and 14 patients with alcoholic etiology (non-HCV group). Patients with HCV were more likely to have severe infections (80%) in comparison with patients in the non-HCV group (42%) (P=0.05). The HCV group had a 3-fold greater likelihood of early severe bacterial infections than the non-HCV group. At 1 week post LT, the HCV group showed higher values of CD19+ B cells/microL than the non-HCV group (P<0.05). At weeks 4 and 12 post LT, the HCV group had lower values of CD19+ B cells/microL (P<0.05). Our data suggest that HCV recurrence after LT was associated with a high incidence of early severe infections and immunological alterations, which may be related to this increased risk.

Humoral and cellular immune monitoring might be useful to identify liver transplant recipients at risk for development of infection.

Orthotopic liver transplantation (OLT) is a successful therapy for patients with end-stage liver disease, and infection remains a significant cause of morbidity and mortality for patients undergoing this procedure. To assess humoral and cellular immunity markers as potential risk factors for development of infection, 46 consecutive liver transplant recipients (hepatitis C virus cirrhosis [n=17], alcoholic liver disease [n=15], hepatocellular carcinoma [n=9], autoimmune hepatitis [n=2], and other [n=3]) performed at a single center were prospectively studied. Maintenance therapy included tacrolimus (n=37) or cyclosporine (n=9) and prednisone. During follow-up, 27 patients had at least 1 episode of infection (58.7%). Pre-OLT immunoglobulin G (IgG) hypergammaglobulinemia (relative risk [RR] 2.78; 95% confidence interval [CI], 1.17-6.60, P=0.02), pre-OLT IgA hypergammaglobulinemia (RR 2.77, CI=1.24-6.19, P=0.012), and pre-OLT C3 hypocomplementemia (RR 3.02, CI=1.21-7.55, P=0.018) were associated with an increased risk for development of infection. Monitoring of Ig and complement levels might help to identify the risk of developing infection in OLT.

[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.

Partial response to anti-CD20 monoclonal antibody treatment of severe immune thrombocytopenic purpura in a patient with common variable immunodeficiency.

Immune thrombocytopenic purpura (ITP), alone or in combination with autoimmune hemolytic anemia (Evans syndrome) and/or autoimmune neutropenia, is frequent in patients with common variable immunodeficiency (CVID). A 34-year-old man with CVID had long-standing unresponsive ITP. The patient had a 9-year history of CVID on substitutive therapy with intravenous immunoglobulin (IVIG). The clinical course of CVID was complicated with refractory fistulizing inflammatory bowel disease, nodular regenerative hyperplasia of the liver, splenomegaly, severe portal hypertension, and hypercatabolism of IgG. ITP was refractory to medical therapy, including different combinations of corticosteroids, high-dose IVIG, azathioprine, and vincristine. Splenectomy was not performed because of severe portal hypertension. He received a total five doses of rituximab, a monoclonal antibody directed against CD20 antigen, at a dose of 375 mg/m(2). After an initially slow response, his platelet count increased to more than 50,000/microL by the fourth week of infusion. Therapy was well tolerated, and B lymphocytes were effectively depleted from the peripheral blood. The patient was completely tapered off glucocorticoids and maintained platelets at above 40,000/microL. The patient has not taken immunosuppressive agents for 11 months. Early treatment with rituximab might be an option for patients with CVID and ITP that do not respond to other treatments or for patients for whom a splenectomy is contraindicated.

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.

Hypocomplementemia in the absence of autoantibodies in women with recurrent pregnancy loss.

BACKGROUND: Accumulating data suggest an immunopathogenic role for the complement system as a causative element in pregnancy loss (PL). Formation of pathogenic antibodies with activation of the classical pathway may have a role, but this mechanism fails to characterize the majority of cases with recurrent PL. We established the prevalence of hypocomplementemia without circulating autoantibodies in women with recurrent PL. METHODS: In a retrospective case control study, 201 women with recurrent PL (two or more PL) and 30 healthy women who had normal pregnancies but no PL were studied. Serum levels of C3, C4, and factor B were determined by nephelometry. Total hemolytic activity of the complement system (CH100) was investigated by radial immunodiffusion test. RESULTS: The prevalence of hypocomplementemia [low levels of C3, C4, FB or CH100 (with normal concentrations of C3, C4 and FB)] was significantly higher in women with recurrent PL (22.4%) in comparison with controls (6.6%; p = 0.019). C3, C4, FB hypocomplementemia or low CH100 were observed in 13 (6.5%), 19 (9.4%), 13 (6.5%) and 7 (3.5%) women with recurrent PL, respectively. Among patients with C3, C4, FB or CH100 hypocomplementemia, 10, 18, 12 and 5 patients had no circulating autoantibodies [antinuclear antibodies, anticardiolipin antibodies or antithyroid antibodies], respectively. In all, hypocomplementemia, in the absence of autoantibodies, was observed in 38 (18.9%) women with recurrent PL in a significantly higher frequency than controls (n = 2, p = 0.049). CONCLUSIONS: Hypocomplementemia, in the absence of autoantibodies was observed in a group of women with recurrent PL which might suggest a role of the complement system in the pathogenesis of PL in these patients.

Elevated levels of activated CD4 T cells in common variable immunodeficiency: association with clinical findings.

BACKGROUND: Common variable immunodeficiency (CVID) is a very heterogeneous syndrome defined by impaired immunoglobulin production. The primary defect remains unknown, but many reports describe peripheral blood T and B lymphocyte dysfunctions in a substantial proportion of CVID patients. Immunophenotypic alterations on memory B lymphocytes correlate with clinical findings. A B-cell-oriented classification principle of the patients has been proposed. METHODS AND RESULTS: We investigated the expression of activation surface molecules on CD4 and CD8 T-cells from 14 patients with CVID, 6 non-CVID hypogammaglobulinemic patients with recurrent infections, 47 asymptomatic HIV-positive patients without AIDS defining conditions and 23 healthy subjects. Lymphocyte subsets were analysed by three-colour flow cytometry. Monoclonal panel: CD38-FITC/HLADR-PE/CD4 or CD8-PerCP. In CVID patients serum levels of CD4 T-cells co-expressing the activation marker HLA-DR [CD4+DR+ (34 %), CD4+CD38+DR+ (18 %)] were significantly elevated compared with controls. Significant increases in CD8+DR+ (54%), CD8+ CD38+ (43%) and CD8+CD38+DR+ (29%) T-cells were observed in comparison with healthy controls. CVID patients with splenomegaly, lower pre-infusion IgG levels (< 600 mg/dl), autoimmune or lymphoproliferative conditions demonstrated even higher levels of CD4+CD38+DR+T cells (22, 22, 21 and 21% respectively) compared with other CVID patients (13, 13, 15 and 15% respectively). CONCLUSION: These findings indicate a state of ongoing T lymphocyte activation which is associated with clinical findings frequently observed in CVID.

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.

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

Monitorización inmunológica en mujeres con aborto recurrente / Immunological monitoring in women with recurrent spontaneous abortions

Para evaluar la prevalencia de alteraciones inmunológicas en pacientes con aborto espontáneo recurrente realizamos un estudio retrospectivo transversal. Las mujeres estudiadas habían sido evaluadas previamente mediante cariotipo de pareja y ecografía para investigar alteración anatómica. La monitorización inmunológica de rutina incluyó anticuerpos antifosfolípidos (in = 333), anticuerpos anticardiolipina (ACA), anticoagulante lúpico], anticuerpos anti-beta-2 glucoproteína-I (n = 139) [anticuerpos antinucleares (n = 333), anticuerpos antitiroideos (n = 180) y evaluación del porcentaje de células natural killer (NK) en sangre periférica (n = 189) en 333 pacientes consecutivas con 2 o más (intervalo 2-12) abortos espontáneos recurrentes. Se detectaron anticuerpos antifosfolípidos (ACA a valor moderado-alto o anticoagulante lúpico) en un 15,9% de pacientes. Un 6% de las pacientes tuvo anticuerpos antinucleares a título 1:160 o mayor. Se observó un porcentaje elevado de linfocitos CD56+/CD16+CD3­ (> 18%) en el 11,1% de las pacientes. Se documentó positividad de anticuerpos antitiroideos en el 4% de las mujeres. Globalmente, un 28,5% de las mujeres tuvo al menos una alteración inmunológica de las estudiadas. En un estudio realizado en mujeres con aborto espontáneo recurrente se observaron alteraciones autoinmunitarias y aloinmunitarias que involucran distintos autoanticuerpos y células NK de sangre periférica (AU)

We performed a retrospective cross-sectional study to ascertain the prevalence of immunological abnormalities in women with recurrent spontaneous abortions (RSA). The women had previously undergone karyotyping of the couple and ultrasonography to investigate anatomic uterine anomalies before immunological study. Routine immunologic monitoring for circulating antiphospholipid antibodies (aPL, n=333) [anticardiolipin antibodies (aCL), lupus anticoagulant (LA)], anti-beta-2 glycoprotein-I antibodies (n=139), antinuclear antibodies (n=333), antithyroid antibodies (n=180) and percentages of natural killer (NK) cells in peripheral blood (n=189) was carried out in 333 consecutive patients with two or more (range 2-12) RSA. aPL positivity (mean-high value aCL or LA) was 15.9%. The frequency of positive antinuclear antibody tests at a titer of 1:160 or higher was 6%. Elevated levels of CD56+/CD16+CD32 lymphocytes (>18%) were observed in 11.1% of the patients studied. Anti-thyroid antibody positivity was found in 4% of women. Overall, 28.5% of women had at least one immunological abnormality. Women with RSA had significant autoimmune and alloimmune alterations involving functionally distinct autoantibodies and peripheral blood NK cells (AU)

Hypocomplementemia in the absence of autoantibodies in women with recurrent pregnancy loss / Hipocomplementemia en ausencia de autoanticuerpos en mujeres con abortos repetidos

Background. Accumulating data suggest an immunopathogenic role for the complement system as a causative element in pregnancy loss (PL). Formation of pathogenic antibodies with activation of the classical pathway may have a role, but this mechanism fails to characterize the majority of cases with recurrent PL. We established the prevalence of hypocomplementemia without circulating autoantibodies in women with recurrent PL. Methods: In a retrospective case control study, 201 women with recurrent PL (two or more PL) and 30 healthy women who had normal pregnancies but no PL were studied. Serum levels of C3, C4, and factor B were determined by nephelometry. Total hemolytic activity of the complement system (CH100) was investigated by radial immunodiffusion test. Results: The prevalence of hypocomplementemia [low levels of C3, C4, FB or CH100 (with normal concentrations of C3, C4 and FB)] was significantly higher in women with recurrent PL (22,4 %) in comparison with controls (6.6 %; p = 0.019). C3, C4, FB hypocomplementemia or low CH100 were observed in 13 (6,5 %), 19 (9,4 %), 13 (6.5 %) and 7 (3,5 %) women with recurrent PL, respectively. Among patients with C3, C4, FB or CH100 hypocomplementemia, 10, 18, 12 and 5 patients had no circulating autoantibodies [antinuclear antibodies, anticardiolipin antibodies or antithyroid antibodies], respectively. In all, hypocomplementemia, in the absence of autoantibodies, was observed in 38 (18,9 %) women with recurrent PL in a significantly higher frequency than controls (n = 2, p = 0.049). Conclusions: Hypocomplementemia, in the absence of autoantibodies was observed in a group of women with recurrent PL which might suggest a role of the complement system in the pathogenesis of PL in these patients

Antecedentes. Un cúmulo de datos sugiere que el sistema complemento juega un papel destacado como elemento inmunopatogénico en la interrupción espontánea del embarazo. La formación de anticuerpos patógenos que activen la vía clásica del complemento puede jugar un papel, pero este mecanismo falla al caracterizar la mayoría de los casos de aborto recurrente. Nosotros establecemos la prevalencia de la hipocomplementemia sin anticuerpos circulantes en mujeres con abortos recurrentes. Métodos. En un estudio retrospectivo se estudiaron 201 mujeres con aborto recurrente (2 o más abortos) y 30 mujeres sanas que habían tenido embarazos normales, pero no abortos. Por nefelometría se valoraron los niveles de C3, C4 y factor B. La actividad del sistema complemento (CH100) se estudio por inmunodifusión radial. Resultados. La prevalencia de hypocomplementemia (niveles bajos de C3, C4, FB o CH100 –con concentraciones normales de C3, C4 y FB) fue significativamente más elevada en mujeres con aborto recurrente (22,4%) en comparación con los controles (6,6%; p=0.019). C3, C4, hypocomplementemia FB o CH100 bajo, se observaron respectivamente en 13 (6,6%), 19 (9,4%), 13 (6,5%) y 7 (3,5%) de mujeres con abortos repetidos. Entre las pacientes con C3, C4, FB o CH100 hipocomplementemia, 10, 18, 12 y 5, respectivamente no tenían autoanticuerpos circulantes (anticuerpos antinucleares, anticardiolipina o antitiroides). En todas, hipocomplementemia en ausencia de autoanticuerpos, se observó en 38 (18,9%) mujeres con aborto recurrente y con una significativa mayor frecuencia que en los controles (n=2, p=0.049). Conclusiones. Hipocomplementemia en ausencia de autoanticuerpos se observó en un grupo de mujeres con aborto recurrente, lo que podría sugerir el papel del sistema complemento en la patogénesis de los abortos de estas pacientes