Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1.

The activating natural killer (NK)-cell receptor KIR3DS1 has been linked to the outcome of various human diseases, including delayed progression of disease caused by human immunodeficiency virus type 1 (HIV-1), yet a ligand that would account for its biological effects has remained unknown. We screened 100 HLA class I proteins and found that KIR3DS1 bound to HLA-F, a result we confirmed biochemically and functionally. Primary human KIR3DS1(+) NK cells degranulated and produced antiviral cytokines after encountering HLA-F and inhibited HIV-1 replication in vitro. Activation of CD4(+) T cells triggered the transcription and surface expression of HLA-F mRNA and HLA-F protein, respectively, and induced binding of KIR3DS1. HIV-1 infection further increased the transcription of HLA-F mRNA but decreased the binding of KIR3DS1, indicative of a mechanism for evading recognition by KIR3DS1(+) NK cells. Thus, we have established HLA-F as a ligand of KIR3DS1 and have demonstrated cell-context-dependent expression of HLA-F that might explain the widespread influence of KIR3DS1 in human disease.

Ebola virus disease: An emerging and re-emerging viral threat.

The genus Ebolavirus from the family Filoviridae is composed of five species including Sudan ebolavirus, Reston ebolavirus, Bundibugyo ebolavirus, Taï Forest ebolavirus, and Ebola virus (previously known as Zaire ebolavirus). These viruses have a large non-segmented, negative-strand RNA of approximately 19 kb that encodes for glycoproteins (i.e., GP, sGP, ssGP), nucleoproteins, virion proteins (i.e., VP 24, 30,40) and an RNA dependent RNA polymerase. These viruses have become a global health concern because of mortality, their rapid dissemination, new outbreaks in West-Africa, and the emergence of a new condition known as "Post-Ebola virus disease syndrome" that resembles inflammatory and autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis with uveitis. However, there are many gaps in the understanding of the mechanisms that may induce the development of such autoimmune-like syndromes. Some of these mechanisms may include a high formation of neutrophil extracellular traps, an uncontrolled "cytokine storm", and the possible formation of auto-antibodies. The likely appearance of autoimmune phenomena in Ebola survivors suppose a new challenge in the management and control of this disease and opens a new field of research in a special subgroup of patients. Herein, the molecular biology, pathogenesis, clinical manifestations, and treatment of Ebola virus disease are reviewed and some strategies for control of disease are discussed.

Bystander activation and autoimmunity.

The interaction over time of genetic, epigenetic and environmental factors (i.e., autoimmune ecology) increases or decreases the liability an individual would have to develop an autoimmune disease (AD) depending on the misbalance between risk and protective effects. Pathogens have been the most common antecedent events studied, but multiple other environmental factors including xenobiotic chemicals, drugs, vaccines, and nutritional factors have been implicated into the development of ADs. Three main mechanisms have been offered to explain the development of autoimmunity: molecular mimicry, epitope spreading, and bystander activation. The latter is characterized by auto-reactive B and T cells that undergo activation in an antigen-independent manner, influencing the development and course of autoimmunity. Activation occurs due to a combination of an inflammatory milieu, co-signaling ligands, and interactions with neighboring cells. In this review, we will discuss the studies performed seeking to define the role of bystander activation in systemic and organ-specific ADs. In all cases, we are cognizant of individual differences between hosts and the variable latency time for clinical expression of disease, all of which have made our understanding of the etiology of loss of immune tolerance difficult and enigmatic.

Cluster analysis of autoimmune rheumatic diseases based on autoantibodies. New insights for polyautoimmunity.

Autoimmune diseases (ADs) are a chronic and clinically heterogeneous group of diseases characterized by share common immunopathogenic mechanisms and risk factors (i.e., the autoimmune tautology), which explain the fact that one AD may coexist with others (i.e., polyautoimmunity - PolyA). In the present exploratory study, a mixed-cluster analysis of the most common autoimmune rheumatic diseases (ARDs) was done. A total of 187 consecutive women with established systemic lupus erythematosus (n = 70), rheumatoid arthritis (n = 51), systemic sclerosis (n = 35) and Sjögren's syndrome (n = 31) were included. A comprehensive clinical, autoantibody and cytokine assessment was simultaneously done. Total PolyA was registered in 142 (75.9%) patients. Six clusters were obtained, built mainly on autoantibodies: PolyA-I to -VI. The PolyA-III cluster showed the highest frequency of overt PolyA (p = 0.01), and the PolyA-I, -III, and -IV clusters exhibited the highest positivity for IL-12/23p40 (p = 0.015). These results provide new insights into the pathophysiology of PolyA and warrant prospective validation to enable development of a more accurate taxonomy of ARDs.

Cytokine imbalance in patients with systemic sclerosis and resilience: the key role of interleukin-6.

OBJECTIVES: Resilience, the ability to respond positively to adverse events, may be influenced by long-term stressors and autoimmune/inflammatory conditions such as systemic sclerosis (SSc). Since the immune system plays a role in the development of resilience, we aimed to evaluate the relationship between a panel of cytokines and resilience in patients with SSc. METHODS: Thirty-five consecutive women with established SSc were involved in this exploratory study. Clinical characteristics, including severity of symptoms and resilience, a panel of 15 serum cytokines and 17 autoantibodies were assessed simultaneously. Multivariate methods were used to analyse the data. RESULTS: Interleukin-6 (IL-6) levels were associated with severity of symptoms (ß=1.8395, p=0.04), and low resilience scores (ß= -0.581120, p=0.02). Furthermore, resilience was not associated with clinical manifestations nor polyautoimmunity. Cytokine levels did not significantly differ between groups based on regular physical activity. CONCLUSIONS: The results highlight the importance of IL-6 as a key mediator in the altered cytokine network of SSc.

Molecular mimicry and autoimmunity.

Molecular mimicry is one of the leading mechanisms by which infectious or chemical agents may induce autoimmunity. It occurs when similarities between foreign and self-peptides favor an activation of autoreactive T or B cells by a foreign-derived antigen in a susceptible individual. However, molecular mimicry is unlikely to be the only underlying mechanism for autoimmune responses; other factors such as breach in central tolerance, non-specific bystander activation, or persistent antigenic stimuli (amongst others) may also contribute to the development of autoimmune diseases. Host genetics, exposure to microbiota and environmental chemicals are additional links to our understanding of molecular mimicry. Our current knowledge of the detailed mechanisms of molecular mimicry is limited by the issues of prolonged periods of latency before the appearance of disease, the lack of enough statistical power in epidemiological studies, the limitations of the potential role of genetics in human studies, the relevance of inbred murine models to the diverse human population and especially the limited technology to systematically dissect the human T-cell repertoire and B-cell responses. Nevertheless, studies on the role of autoreactive T-cells that are generated secondary to molecular mimicry, the diversity of the T-cell receptor repertoires of auto-reactive T-cells, the role of exposure to cryptic antigens, the generation of autoimmune B-cell responses, the interaction of microbiota and chemical adjuvants with the host immune systems all provide clues in advancing our understanding of the molecular mechanisms involved in the evolving concept of molecular mimicry and also may potentially aid in the prevention and treatment of autoimmune diseases.

Cytokine and autoantibody clusters interaction in systemic lupus erythematosus.

BACKGROUND: Evidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in a highly complex network. Thus, understanding how these complex nonlinear processes are connected and observed in real-life settings is a major challenge. Cluster approaches may assist in the identification of these subphenotypes, which represent such a phenomenon, and may contribute to the development of personalized medicine. Therefore, the relationship between autoantibody and cytokine clusters in SLE was analyzed. METHODS: This was an exploratory study in which 67 consecutive women with established SLE were assessed. Clinical characteristics including disease activity, a 14-autoantibody profile, and a panel of 15 serum cytokines were measured simultaneously. Mixed-cluster methodology and bivariate analyses were used to define autoantibody and cytokine clusters and to identify associations between them and related variables. RESULTS: First, three clusters of autoantibodies were defined: (1) neutral, (2) antiphospholipid antibodies (APLA)-dominant, and (3) anti-dsDNA/ENA-dominant. Second, eight cytokines showed levels above the threshold thus making possible to find 4 clusters: (1) neutral, (2) chemotactic, (3) G-CSF dominant, and (4) IFNα/Pro-inflammatory. Furthermore, the disease activity was associated with cytokine clusters, which, in turn, were associated with autoantibody clusters. Finally, when all biomarkers were included, three clusters were found: (1) neutral, (2) chemotactic/APLA, and (3) IFN/dsDNA, which were also associated with disease activity. CONCLUSION: These results support the existence of three SLE cytokine-autoantibody driven subphenotypes. They encourage the practice of personalized medicine, and support proof-of-concept studies.

Original antigenic sin: A comprehensive review.

The concept of "original antigenic sin" was first proposed by Thomas Francis, Jr. in 1960. This phenomenon has the potential to rewrite what we understand about how the immune system responds to infections and its mechanistic implications on how vaccines should be designed. Antigenic sin has been demonstrated to occur in several infectious diseases in both animals and humans, including human influenza infection and dengue fever. The basis of "original antigenic sin" requires immunological memory, and our immune system ability to autocorrect. In the context of viral infections, it is expected that if we are exposed to a native strain of a pathogen, we should be able to mount a secondary immune response on subsequent exposure to the same pathogen. "Original antigenic sin" will not contradict this well-established immunological process, as long as the subsequent infectious antigen is identical to the original one. But "original antigenic sin" implies that when the epitope varies slightly, then the immune system relies on memory of the earlier infection, rather than mount another primary or secondary response to the new epitope which would allow faster and stronger responses. The result is that the immunological response may be inadequate against the new strain, because the immune system does not adapt and instead relies on its memory to mount a response. In the case of vaccines, if we only immunize to a single strain or epitope, and if that strain/epitope changes over time, then the immune system is unable to mount an accurate secondary response. In addition, depending of the first viral exposure the secondary immune response can result in an antibody-dependent enhancement of the disease or at the opposite, it could induce anergy. Both of them triggering loss of pathogen control and inducing aberrant clinical consequences.

Simultaneous TCR and CD244 signals induce dynamic downmodulation of CD244 on human antiviral T cells.

Various cosignaling molecules on T cells can contribute to activation, inhibition, or exhaustion, depending on context. The surface receptor signaling lymphocytic activation molecule (SLAM) family receptor CD244 (2B4/SLAMf4) has been shown to be capable of either inhibitory or enhancing effects upon engagement of its ligand CD48 (SLAMf2). We examined phenotypes of CD8 T cells from HIV(+) and HIV(neg) human donors, specific for HIV and/or respiratory syncytial virus. Cultured and ex vivo CD8 T cells expressed PD-1, CD244, and TIM-3. We found that ex vivo CD8 T cells downregulated CD244 in response to superantigen. Furthermore, cognate peptide induced rapid downregulation of both CD244 and TIM-3, but not PD-1, on CD8 T cell clones. CD244 downmodulation required simultaneous signaling via both TCR and CD244 itself. Using a pH-sensitive fluorophore conjugated to avidin-Ab tetramers, we found that CD244 crosslinking in the presence of TCR signaling resulted in rapid transport of CD244 to an acidic intracellular compartment. Downregulation was not induced by PMA-ionomycin, or prevented by PI3K inhibition, implicating a TCR-proximal signaling mechanism. CD244 internalization occurred within hours of TCR stimulation and required less peptide than was required to induce IFN-γ production. The degree of CD244 internalization varied among cultured CD8 T cell lines of different specificities, and correlated with the enhancement of IFN-γ production in response to CD48 blockade in HIV(+), but not HIV(neg), subjects. Our results indicate that rapid CD244 internalization is induced by a two-signal mechanism and plays a role in modulation of antiviral CD8 T cell responses by CD48-CD244 signaling.

The immune response to the RT181-189 epitope in HIV-1-infected patients is associated with viral sequence polymorphism flanking the epitope.

Many drug-resistance mutations in HIV-1 reverse transcriptase fall within cytotoxic T lymphocytes (CTL) epitopes, but studies of the response to these epitopes in patients with virological failure are lacking. We therefore compared IFN-γ ELISPOT responses to the YV9 epitope (RT181-189) covering the lamivudine resistance mutation, M184V, in HLA-A2(+) antiretroviral treatment (ART)-naive patients (n = 19), to those found in HLA-A2(+) patients with virological failure (n = 15). Ten ART-naive patients had an ELISPOT response to the wild-type epitope that cross-reacted with the mutant epitope. Two patients with virological failure showed a specific response to the 184V mutant epitope. Responses against YV9 were strongly associated (p = 0.005) with the presence of a 177E mutation, and the same tendency was observed in an independent cohort of patients (n = 22). These results indicate that variants in flanking residues may influence CTL responses to conserved subdominant HIV-1 epitopes.

Latent autoimmune thyroid disease.

OBJECTIVE: To determine the prevalence of thyroid autoantibodies and the associated factors in euthyroid subjects. METHODS: 300 euthyroid subjects, chosen by stratified sampling from an inception cohort of 1335 individuals, were included. Thyroid function was evaluated by measuring the serum levels of TSH (0.3-4.5 µIU/mL) and FT4 (5.2-12.7µg/dL). Anti-peroxidase (TPOAbs), anti-thyroglobulin (TgAbs), and anti-TSH receptor (TrAbs) antibodies were evaluated with 23 additional autoantibodies as well as vitamin D (VitD) levels. The analysis included sociodemographic, clinical, and environmental characteristics. Data were analyzed by bivariate and multivariate tests. RESULTS: Thyroid autoimmunity was observed in 15.3% of the subjects (TPOAbs 11.3% and TgAbs 2.0%). In six individuals, both autoantibodies were positive. TrAbs were not detected in any individual. Familial thyroid disease (ߠ​= â€‹3.4, 95% CI: 1.2-9.5, P â€‹= â€‹0.021), the presence of other autoimmune diseases (ߠ​= â€‹10.8, 95% CI: 1.6-72.9, P â€‹= â€‹0.014) VitD insufficiency (P â€‹= â€‹0.030), never smoke (ߠ​= â€‹6.9, 95% CI: 1.6-30.4, P â€‹= â€‹0.010), drinking more than 4 cups of coffee (ߠ​= â€‹3.8, 95% CI: 1.1-13.1, P â€‹= â€‹0.036), and a higher number of years exposed to wood smoke (P â€‹= â€‹0.04) were associated with thyroid autoimmunity. In the case of TPOAbs, familial thyroid disease (ߠ​= â€‹4.9, 95% CI: 1.7-14.0, P â€‹= â€‹0.003), never smoke (ߠ​= â€‹5.7, 95% CI: 1.4-21.0, P â€‹= â€‹0.002), and drinking more than 4 cups of coffee (ߠ​= â€‹3.6, 95% CI: 1.1-13.1, P â€‹= â€‹0.047) were associated with their positivity. In addition, the presence of anti-SS-A/Ro52 (ߠ​= â€‹36.7, 95% CI: 2.5-549.9, P â€‹= â€‹0.009) and anti-Ku antibodies (ߠ​= â€‹10.2, 95% CI: 1.1-100.7, P â€‹= â€‹0.046) was also associated with TPOAbs. The presence of African ancestry (ߠ​= â€‹10.5, 95% CI: 1.7-63.2, P â€‹= â€‹0.01), anti-SS-A/Ro52 (ߠ​= â€‹15.8, 95% CI: 1.2-198.6, P â€‹= â€‹0.03), and anti-CENP-B antibodies (ߠ​= â€‹31.2, 95% CI: 1.8-565.9 â€‹P â€‹= â€‹0.02) were associated with TgAbs. CONCLUSION: Latent thyroid autoimmunity is not rare. Environmental, genetic, and immunological factors as well as ancestry are associated risk factors. These results would facilitate the implementation of screening strategies in order to provide timely diagnosis and treatment.

HIV Controllers Exhibit Effective CD8+ T Cell Recognition of HIV-1-Infected Non-activated CD4+ T Cells.

Even with sustained antiretroviral therapy, resting CD4+ T cells remain a persistent reservoir of HIV infection, representing a critical barrier to curing HIV. Here, we demonstrate that CD8+ T cells recognize infected, non-activated CD4+ T cells in the absence of de novo protein production, as measured by immune synapse formation, degranulation, cytokine production, and killing of infected cells. Immune recognition is induced by HLA-I presentation of peptides derived from incoming viral particles, and recognition occurred either following cell-free virus infection or following cell-to-cell spread. CD8+ T cells from HIV controllers mediate more effective immune recognition than CD8+ T cells from progressors. These results indicate that non-activated HIV-infected CD4+ T cells can be targeted by CD8+ T cells directly after HIV entry, before reverse transcription, and thus before the establishment of latency, and suggest a mechanism whereby the immune response may reduce the size of the HIV reservoir.

Sjögren's Syndrome and Autoimmune Thyroid Disease: Two Sides of the Same Coin.

The coexistence of Sjögren's syndrome (SS) and autoimmune thyroid disease (AITD) has been documented. However, there is no consensus whether this coexistence should be considered as the same nosological condition or as polyautoimmunity. Thus, in this monocentric retrospective study, patients with SS alone (i.e., primary) were compared with patients with SS and AITD. In addition, a discussion of previous studies including those about genetic and environmental factors influencing the development of both conditions is presented. In our series, all patients with AITD had Hashimoto's thyroiditis (HT). No significant differences in age, gender, age of disease onset, and disease duration were found between the two groups. Lymphadenopathy and urticaria were more frequently registered in patients with SS-HT than in patients with SS alone (p < 0.05). Anti-Ro/SSA antibodies were more frequent in the primary SS group (p = 0.01). SS-HT patients were more likely to report a positive history of smoking (p = 0.03). The clinical expression of SS varies slightly when HT coexists. Although both entities share common physiopathological mechanisms as part of the autoimmune tautology, they are nosologically different and their coexistence should be interpreted as polyautoimmunity. Further studies based on polyautoimmunity would allow establishing a new taxonomy of autoimmune diseases.

Mayaro: an emerging viral threat?

Mayaro virus (MAYV), an enveloped RNA virus, belongs to the Togaviridae family and Alphavirus genus. This arthropod-borne virus (Arbovirus) is similar to Chikungunya (CHIKV), Dengue (DENV), and Zika virus (ZIKV). The term "ChikDenMaZika syndrome" has been coined for clinically suspected arboviruses, which have arisen as a consequence of the high viral burden, viral co-infection, and co-circulation in South America. In most cases, MAYV disease is nonspecific, mild, and self-limited. Fever, arthralgia, and maculopapular rash are among the most common symptoms described, being largely indistinguishable from those caused by other arboviruses. However, severe manifestations of the infection have been reported, such as chronic polyarthritis, neurological complications, hemorrhage, myocarditis, and even death. Currently, there are no specific commercial tools for the diagnosis of MAYV, and the use of serological methods can be affected by cross-reactivity and the window period. A diagnosis based on clinical and epidemiological data alone is still premature. Therefore, new entomological research is warranted, and new highly specific molecular diagnostic methods should be developed. This comprehensive review is intended to encourage public health authorities and scientific communities to actively work on diagnosing, preventing, and treating MAYV infection.

Resilience in women with autoimmune rheumatic diseases.

OBJECTIVE: To evaluate the relationship between resilience and clinical outcomes in patients with autoimmune rheumatic diseases. METHODS: Focus groups, individual interviews, and chart reviews were done to collect data on 188 women with autoimmune rheumatic diseases, namely rheumatoid arthritis (n=51), systemic lupus erythematosus (n=70), systemic sclerosis (n=35), and Sjögren's syndrome (n=32). Demographic, clinical, and laboratory variables were assessed including disease activity by patient reported outcomes. Resilience was evaluated by using the Brief Resilience Scale. Bivariate, multiple linear regression, and classification and regression trees were used to analyse data. RESULTS: Resilience was influenced by age, duration of disease, and socioeconomic status. Lower resilience scores were observed in younger patients (<48years) with systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis who had low socioeconomic status, whereas older patients (>50years) had higher resilience scores regardless of socioeconomic status. There was no influence of disease activity on resilience. A particular behaviour was observed in systemic sclerosis in which patients with high socioeconomic status and regular physical activity had higher resilience scores. CONCLUSION: Resilience in patients with autoimmune rheumatic diseases is a continuum process influenced by age and socioeconomic status. The ways in which these variables along with exercise influence resilience deserve further investigation.

Guillain-Barré syndrome, transverse myelitis and infectious diseases.

Guillain-Barré syndrome (GBS) and transverse myelitis (TM) both represent immunologically mediated polyneuropathies of major clinical importance. Both are thought to have a genetic predisposition, but as of yet no specific genetic risk loci have been clearly defined. Both are considered autoimmune, but again the etiologies remain enigmatic. Both may be induced via molecular mimicry, particularly from infectious agents and vaccines, but clearly host factor and co-founding host responses will modulate disease susceptibility and natural history. GBS is an acute inflammatory immune-mediated polyradiculoneuropathy characterized by tingling, progressive weakness, autonomic dysfunction, and pain. Immune injury specifically takes place at the myelin sheath and related Schwann-cell components in acute inflammatory demyelinating polyneuropathy, whereas in acute motor axonal neuropathy membranes on the nerve axon (the axolemma) are the primary target for immune-related injury. Outbreaks of GBS have been reported, most frequently related to Campylobacter jejuni infection, however, other agents such as Zika Virus have been strongly associated. Patients with GBS related to infections frequently produce antibodies against human peripheral nerve gangliosides. In contrast, TM is an inflammatory disorder characterized by acute or subacute motor, sensory, and autonomic spinal cord dysfunction. There is interruption of ascending and descending neuroanatomical pathways on the transverse plane of the spinal cord similar to GBS. It has been suggested to be triggered by infectious agents and molecular mimicry. In this review, we will focus on the putative role of infectious agents as triggering factors of GBS and TM.

Autoimmune Neurological Conditions Associated With Zika Virus Infection.

Zika virus (ZIKV) is an emerging flavivirus rapidly spreading throughout the tropical Americas. Aedes mosquitoes is the principal way of transmission of the virus to humans. ZIKV can be spread by transplacental, perinatal, and body fluids. ZIKV infection is often asymptomatic and those with symptoms present minor illness after 3 to 12 days of incubation, characterized by a mild and self-limiting disease with low-grade fever, conjunctivitis, widespread pruritic maculopapular rash, arthralgia and myalgia. ZIKV has been linked to a number of central and peripheral nervous system injuries such as Guillain-Barré syndrome (GBS), transverse myelitis (TM), meningoencephalitis, ophthalmological manifestations, and other neurological complications. Nevertheless, mechanisms of host-pathogen neuro-immune interactions remain incompletely elucidated. This review provides a critical discussion about the possible mechanisms underlying the development of autoimmune neurological conditions associated with Zika virus infection.

Zika virus and autoimmunity. One-step forward.

Zika virus (ZIKV) infection has been associated with the development of Guillain-Barré syndrome (GBS) and idiopathic thrombocytopenic purpura (ITP). Whether ZIKV infection is related to other autoimmune diseases is unknown. Therefore, an association study to evaluate rheumatic and thyroid autoimmunity in patients with ZIKV disease was conducted through a panel of 14 autoantibodies. In addition, a literature review on ZIKV, and GBS and ITP was performed. Our results disclosed a lack of association of rheumatoid and thyroid autoimmunity with ZIKV disease. A total of 272 cases of GBS related to ZIKV were retrieved from the literature, the majority of them being males (54.8%). Electrophysiological findings indicated acute inflammatory demyelinating polyneuropathy as the most frequent subphenotype (75.7%). Up to date, twenty-four cases of ITP in patients with ZIKV disease have been published. Although a few fatal cases have been observed, most of the reported patients responded well to immunomodulatory treatment. A review of the mechanisms incriminated into the development of autoimmune phenomenon in ZIKV disease indicates molecular mimicry as the most plausible one. Nevertheless, more research aimed at deciphering ZIKV disease pathogenesis and its relationship with autoimmunity is warranted.

Discordancia entre métodos de detección de autoanticuerpos / Discrepancy between methods of detection of autoantibodies

Introducción: Las enfermedades autoinmunes sistémicas se caracterizan por la producción de diferentes autoanticuerpos contra antígenos intracelulares. En lupus eritematoso sistémico (LES) los autoanticuerpos son principalmente contra antígenos nucleares, los más frecuentes son los anti-ADN de doble cadena (anti-dsDNA) seguido de los antígenos nucleares extractables (ENAs) los cuales son componentes citoplasmáticos y nucleares solubles con más de 100 antígenos. Los ENAs están presentes también en el síndrome de Sjögren (SS) siendo más frecuentes los anti-Ro y anti-La. Contar con métodos fiables de detección de autoanticuerpos es necesario para el diagnóstico de estas enfermedades. Objetivo: Evaluar la concordancia de tres métodos de detección de anticuerpos antinucleares.