RESUMO
Immune dysregulation is an important aspect of schizophrenia (SZ) and bipolar disorders (BD) pathophysiology, including not only inflammatory but also autoimmune process reflective of abnormal humoral immune responses. Given that B cell-activating factor (BAFF) is an integral aspect of B lymphocyte regulation, the current study investigated BAFF in SZ and BD. 255 SZ patients, 407 BD patients and 185 healthy controls (HC) were investigated across three aspects of soluble BAFF (sBAFF) by (i) comparing sBAFF circulatory levels across SZ, BD and HC, (ii) determining potential correlations between the circulating levels of sBAFF and the genotype distribution of a functionally relevant polymorphism, namely the TNFSF13B 3'UTR insertion-deletion polymorphism (GCTGT>A), (iii) analyzing relationships between both sBAFF levels and 3'UTR insertion-deletion genotypes and disease risk, patients clinical characteristics and circulating levels of potent inflammatory molecules. In addition, in subsets of patients, we also searched for possible correlations between sBAFF levels and stigma of past infectious events as well as positivity for circulating systemic autoantibodies or those directed against central nervous system (CNS) structures. Studying blood derived serum and DNA, weobserved that circulating sBAFF levels were significantly higher in SZ and BD patients, versus HC (p = 5.3*10-10and p = 4.4*10-09). Patients experiencing acute episodes, versus stable patients, in between acute episodes, exhibited higher sBAFF levels (p = 0.017).In SZ patients, positive correlations were observed between elevated sBAFF levels and: (i) elevated positive psychotic symptoms (PANSS pos), (ii) history of childhood trauma (physical abuse), and (iii) low scores on global functioning (GAF) (p = 0.024, p = 0.024, and p = 0.041).We also found that the distribution of the BAFF Ins/Del genotypes was significantly correlated with circulating sBAFF levels in SZ and BD patients (p = 0.0004). Elevated sBAFF levels were also correlated with increased levels of pro-inflammatory markers in both SZ and BD cohorts (p < 0.001). Regarding infectious stigma, only patients seropositive, versus seronegative, for herpes simplex virus (HSV)1 immunoglobulin (Ig)G antibodies exhibited a significant association with high sBAFF levels (p = 0.013). In contrast, positivity for systemic or CNS autoantibodies was significantly associated with reduced sBAFF levels, compared to patients without autoantibodies (p = 0.0017). Overall, our findings indicate that BAFF may be a promising trans-nosographic biomarker of inflammation that is likely to offer predictive, diagnostic, and prognostic tools for the management of SZ and BD. The results therefore have practicable clinical utility given the availability of immunotherapeutic treatment options including targeted monoclonal antibodies against BAFF.
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Unicentric Castleman disease (UCD) is a lymphoproliferative disease of unknown cause. Paraneoplastic pemphigus (PNP) is a major complication shown to be associated with a poor prognosis, with particular severity in patients with bronchiolitis obliterans (BO). This study describes the clinical and biological characteristics of UCD-PNP patients in a large Western cohort. A total of 148 patients diagnosed with UCD were identified, including 14 patients with a defined PNP. PNP was significantly associated with myasthenia gravis (MG) and FDC sarcoma during follow-up (FDCS). PNP was also significantly associated with reduced survival. These data, together with a multivariate analysis by principal components, led to the identification of UCD-PNP as a group at risk of MG, FDCS and death. PDGFRB sequencing performed on UCD lesions from six patients found the gain-of-function p.N666S variant in two. Interestingly, both patients had hyaline-vascular UCD subtype, were in the UCD-PNP subgroup and had FDCS. Sera from 25 UCD-PNP patients and 6 PNP patients without UCD were tested for PNP-associated autoantibodies. Sera from UCD-PNP patients had a strong reactivity against the N-terminal domain of recombinant periplakin (rPPL, 82%) and showed reactivity against at least two domains of rPPL. These features were not found in patients with UCD alone or in the PNP group without UCD. These data indicate that UCD-PNP patients belong to a subgroup sharing strong clinical and biological identity that might help to decipher the different dynamics of UCD natural history.
Assuntos
Hiperplasia do Linfonodo Gigante , Miastenia Gravis , Síndromes Paraneoplásicas , Pênfigo , Humanos , Pênfigo/diagnóstico , Pênfigo/etiologia , Hiperplasia do Linfonodo Gigante/patologia , Autoanticorpos , Miastenia Gravis/diagnóstico , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/diagnósticoRESUMO
Accumulating evidence majorly implicates immune dysfunction in the etiology of psychotic disorders. In particular, altered numbers and functions of natural killer (NK) cells have been described in psychosis, but interpretation has often been confounded by a number of biases, including treatment. Eighty-one first-episode psychosis (FEP) patients who subsequently received a diagnosis of either schizophrenia (SZ; n = 30) or bipolar disorder (BP; n = 31) over a five-year follow-up period were investigated for their NK cell phenotype and compared to 61 healthy controls (HCs). We found a similar proportion of CD3-CD56+ NK cells in FEP patients and HCs. The frequency of NK cells expressing the late cell activation marker HLA-DR was significantly increased in FEP patients compared to HCs, especially in patients with BP (p < 0.0001) and, to a lesser degree, in patients with SZ (p = 0.0128). Interestingly, the expression of the activating NKG2C receptor, known to be associated with infections, was higher in patients with SZ and BP than in HCs (p < 0.0001) and correlated with HLA-DR expression, altogether defining adaptive NK cells. In terms of NK cell function, we observed a suppressed capacity of SZ-derived NK cells to mount cytotoxic responses in the presence of target cells, while NK cells from patients with BP show an inability to produce IFN-γ, a cytokine pivotal to NK function. This study strongly suggests major dysfunction of NK cells in FEP with functioning impairment correlated with psychotic, manic, and depressive symptoms in subsequently diagnosed patients with SZ and BP.
Assuntos
Transtorno Bipolar , Transtornos Psicóticos , Esquizofrenia , Humanos , Imunidade Inata , Células Matadoras NaturaisRESUMO
OBJECTIVES: Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are important for antibacterial immunity and may have regulatory roles. MAIT cells are decreased during SLE. However, their frequencies and phenotype have not been investigated in DM. We studied MAIT cell frequencies and phenotype in DM patients with active and inactive disease (after treatment). METHODS: Peripheral blood flow cytometry analysis of MAIT cells was compared between DM (n = 22), SLE (n = 10), psoriasis (n = 7) and atopic dermatitis (n = 5) patients, and healthy controls (n = 19). RESULTS: A dramatic decrease of circulating MAIT cell frequency was observed in active DM and SLE patients compared with healthy controls and other inflammatory skin diseases [active DM: median = 0.25% (interquartile range 0.19-0.6%), P < 0.0001; active SLE: median = 0.61 (0.55-0.77), P < 0.0001 vs healthy controls: 2.32% (1.18-4.45%)]. MAIT cells from active DM patients had an abnormal phenotype including increased expression of CD25 and cytotoxic T-lymphocyte-associated protein 4 that correlated with their low frequency in the blood. CONCLUSION: In DM, peripheral blood MAIT cells are dramatically reduced and have an activated/exhausted phenotype that may be linked to increased activation-induced cell death.
Assuntos
Dermatomiosite/sangue , Células T Invariantes Associadas à Mucosa/metabolismo , Adulto , Dermatite Atópica/sangue , Feminino , Citometria de Fluxo , Humanos , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Psoríase/sangue , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Immune dysfunction could play a significant role in the pathogenesis of bipolar disorder (BD) and schizophrenia (SZ), conditions with an underlying pro-inflammatory state. Studies on humoral immune responses (which reflects antibody mediated fight against pathogens) in schizophrenia and bipolar disorder are sparse and often providing contradictory results. The aim of this study was to assess humoral immunity in a group of stable bipolar disorder and schizophrenia patients compared to controls by determining total Immunoglobulins and IgG subclasses and to assess their association with latent Toxoplasma gondii and/or CMV infection. METHODS: 334 subjects (124 BD, 75 SZ and 135 Healthy Controls [HC]) were included and tested for humoral immunity by determining the total immunoglobulins (IgG,A and M) and IgG subclasses (IgG1, IgG2, IgG3, IgG4) and their relationship with latent Toxoplasma gondii infection, an established risk factor for BD and SZ. RESULTS: Although lower levels of IgG, IgG1, IgG2, IgG4 and IgA were found among BD as compared to HC and/or SZ, after adjustment for confounding variables, only low levels of IgG and IgG1 in BD remai- ned significant. Strikingly highest levels of antibodies to T. gondii (but not CMV) infection in BD and SZ were associated with lowest levels of IgG3 and IgG4 levels as compared to controls. CONCLUSIONS: Schizophrenia and bipolar disorder patients with latent T. gondii specific infection may be more vulnerable to changes in immuno-inflammatory processes than controls with similar latent infectious state. Simultaneous sequential immunological monitoring both in steady state and active disease phases in the same BD and SZ patients are warranted to understand the role of Toxoplasma gondii latency in these disorders.
Assuntos
Transtorno Bipolar , Imunoglobulinas/sangue , Esquizofrenia , Toxoplasmose/imunologia , Adulto , Transtorno Bipolar/imunologia , Transtorno Bipolar/parasitologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Esquizofrenia/imunologia , Esquizofrenia/parasitologia , Toxoplasma/imunologia , Toxoplasmose/complicações , Adulto JovemRESUMO
Interleukin 10 (IL-10)-producing B cells (regulatory B cells [Bregs]) regulate autoimmunity in mice and humans, and a regulatory role of IL-10-producing plasma cells has been described in mice. Dysfunction of B cells that maintain homeostasis may play a role in the pathogenesis of chronic graft-versus-host disease (cGVHD) after allogeneic stem cell transplantation. Here, we found a relation between decreased Breg frequencies and cGVHD severity. An impaired ability of B cells to produce IL-10, possibly linked to poor signal transducer and activator of transcription 3 and extracellular signal-regulated kinase phosphorylation, was found in patients with active cGVHD. IL-10 production was not confined to a single B-cell subset, but enriched in both the CD24(hi)CD27(+) and CD27(hi)CD38(hi) plasmablast B-cell compartments. In vitro plasmablast differentiation increased the frequency of IL-10-producing B cells. We confirmed that allogeneic transplant recipients had an impaired reconstitution of the memory B-cell pool. cGVHD patients had less CD24(hi)CD27(+) B cells and IL-10-producing CD24(hi)CD27(+) B cells. Patients with cGVHD had increased plasmablast frequencies but decreased IL-10-producing plasmablasts. These results suggest a role of CD24(hi)CD27(+) B-cell and plasmablast-derived IL-10 in the regulation of human cGVHD.
Assuntos
Linfócitos B Reguladores/imunologia , Antígeno CD24/metabolismo , Doença Enxerto-Hospedeiro/imunologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Idoso , Animais , Linfócitos B Reguladores/metabolismo , Linfócitos B Reguladores/patologia , Diferenciação Celular , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Interleucina-10/biossíntese , Sistema de Sinalização das MAP Quinases , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Pessoa de Meia-Idade , Plasmócitos/imunologia , Plasmócitos/metabolismo , Plasmócitos/patologia , Estudos Prospectivos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Adulto JovemAssuntos
Antígenos CD28 , Interferons , Linfócitos T CD8-Positivos , Dermatomiosite , Humanos , Inflamação , Linfócitos TAssuntos
Cútis Laxa/epidemiologia , Cútis Laxa/patologia , Paraproteinemias/epidemiologia , Paraproteinemias/patologia , Adulto , Distribuição por Idade , Idoso , Biópsia por Agulha , Comorbidade , Feminino , Humanos , Imuno-Histoquímica , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos de Amostragem , Índice de Gravidade de Doença , Distribuição por SexoRESUMO
Schnitzler syndrome is a rare plasma cell disorder the pathogenesis of which is still not fully understood. We evaluated the circulating levels of four major angiogenic cytokines (VEGF, angiogenin, angiopoietin-1 and angiopoietin-2) and six bone remodeling markers (sRANKL, osteoprotegerin, dickkopf-1, CTX, osteocalcin and bone-specific alkaline phosphatase-bALP) in 13 patients with Schnitzler syndrome. At diagnosis, patients had elevated angiogenic cytokines. The mean VEGF levels were almost 3.5-fold higher in Schnitzler syndrome compared to controls, while 10 of 13 patients had higher VEGF than the upper control value. Successful treatment led to a significant reduction in VEGF. Patients with Schnitzler syndrome had increased bone formation (high bALP, osteocalcin and osteoprotegerin) which was not balanced by an increase in bone resorption (normal CTX and sRANKL). These data support a role for VEGF as a new minor criterion in the diagnosis and follow up of Schnitzler syndrome, while the uncoupling of bone remodeling in favor of bone formation justifies the presence of bone densification.
Assuntos
Proteínas Angiogênicas/sangue , Antígenos de Diferenciação/sangue , Imunoglobulina M , Neovascularização Fisiológica , Osteogênese , Síndrome de Schnitzler/sangue , Urticária/sangue , Adulto , Idoso , Reabsorção Óssea/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Schnitzler/complicações , Síndrome de Schnitzler/patologia , Urticária/complicações , Urticária/patologiaRESUMO
The MHC class I-related chain A (MICA) molecules exist as membrane-bound and soluble isoforms and are encoded by a polymorphic gene. Their genetic and phenotype characteristics have been studied in various pathologic settings but not in the context of hematopoietic stem cell transplantation (HSCT). Here, we evaluated whether MICA-related features namely MICA-129 gene polymorphism, serum levels of soluble MICA (sMICA) and anti-MICA antibodies (MICA Abs) before and after HSCT could influence the incidence of chronic graft-versus-host disease (cGVHD) and relapse of their disease in 211 HLA-identical sibling pairs and in a subset of 116 recipients, respectively. Although the MICA-129 val/val genotype and elevated sMICA serum levels after HSCT are independently associated with the incidence of cGVHD (P = .002 and .001) regardless of history of acute GVHD, the presence of MICA Abs before transplantation confers protection against cGVHD (P = .04). There is an inverse relationship between MICA Abs and sMICA, suggesting an antibody-based neutralization of deleterious effects of sMICA. Similarly, these genetic and phenotype characteristics of MICA influence the incidence of relapse. Altogether, these data suggest that the studied MICA genotype and phenotype specificities could be used as relevant biomarkers for cGVHD monitoring.
Assuntos
Biomarcadores/análise , Predisposição Genética para Doença/genética , Doença Enxerto-Hospedeiro/diagnóstico , Antígenos de Histocompatibilidade Classe I/genética , Adolescente , Adulto , Silicatos de Alumínio , Anticorpos/análise , Anticorpos/imunologia , Biomarcadores/sangue , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Frequência do Gene , Genótipo , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/genética , Transplante de Células-Tronco Hematopoéticas , Antígenos de Histocompatibilidade Classe I/sangue , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Masculino , Análise Multivariada , Fenótipo , Polimorfismo Genético , Solubilidade , Fatores de Tempo , Adulto JovemAssuntos
Linfócitos B/metabolismo , Doença Enxerto-Hospedeiro/sangue , Transplante de Células-Tronco Hematopoéticas , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Adulto , Idoso , Aloenxertos , Linfócitos B/patologia , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: The impact of reducing immunoglobulin dosage while switching from intravenous to subcutaneous replacement therapy was evaluated. METHODS: Sixty-five patients with primary hypogammaglobulinemia on stable intravenous replacement therapy were included in a monocentric longitudinal trial. IgG trough levels were measured at baseline and during 1 year following the switch to the subcutaneous route. RESULTS: Mean IgG trough level after 12 months of subcutaneous therapy was increased by 5.4 percent (8.37-8.82 g/l, p=0.3), while immunoglobulin dosage had been reduced by 28.3% (151-108 mg/kg/week, p<0.0001). For the patients with the lowest serum IgG level upon intravenous infusions, serum IgG level rose by 37 percent (5.33-7.33 g/l, p=0.003), while mean immunoglobulin dosage was reduced by 36 percent (170-109 mg/kg/week, p=0.04). CONCLUSION: The present study shows that sustained serum IgG levels can be achieved after switching towards subcutaneous replacement despite using reduced immunoglobulin doses.
Assuntos
Agamaglobulinemia/tratamento farmacológico , Imunização Passiva/métodos , Imunoglobulinas/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Imunoglobulinas/sangue , Imunoglobulinas Intravenosas , Infusões Subcutâneas , Estudos LongitudinaisRESUMO
Infections and autoimmunity are associated with autism spectrum disorders (ASD), with both strongly influenced by the genetic regulation of the human leukocyte antigen (HLA) system. The relationship between ASD and the HLA genetic diversity requires further investigation. Using a case control design, the distribution of HLA class II-DRB1 and DQB1 alleles, genotypes and haplotypes were investigated in ASD patients, versus healthy controls (HC). ASD patients meeting DSM-IV TR criteria and HC (474 and 350 respectively) were genotyped at medium resolution using a Luminex-based SSO technology. Comparisons of genotypes, allele frequencies associated with a haplotype analysis were performed. Results indicate: (i) the HLA-DRB1 *11-DQB1*07 haplotype was more prevalent in ASD patients, versus HC (Pc = 0.001), partially replicating previous data and possibly linking to gastro-intestinal (GI)-related pro-inflammatory processes, given that this haplotype associates with pediatric celiac disorders; (ii) the HLA-DRB1 *17-DQB1*02 haplotype was higher in HC, versus ASD patients (Pc = 0.002), indicating that this is a protective haplotype. Using the Autism Diagnostic Interview to assess clinical dimensions, higher scores on social (Pc = 0.006) and non-verbal functioning (Pc = 0.004) associated with the DRB1 *11 DQB1*07 haplotype. Our results support HLA involvement in ASD, with possible relevance to GI and gut-brain axis dysregulation.
Assuntos
Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/patologia , Haplótipos/genética , Antígenos de Histocompatibilidade Classe II/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
BACKGROUND: Chronic low-grade inflammation is believed to contribute, at least in a subset of patients, to the development of bipolar disorder (BD). In this context, the most investigated biological marker is the acute phase response molecule, C-reactive protein (CRP). While the genetic diversity of CRP was amply studied in various pathological settings, little is known in BD. METHODS: 568 BD patients along with 163 healthy controls (HC) were genotyped for the following single-nucleotide polymorphisms (SNPs) on the CRP gene: intron rs1417938 (+ 29) T/A, 3'-UTR rs1130864 (+ 1444) G/A, and downstream rs1205 (+ 1846) (C/T). The statistical analysis was performed using Chi-square testing and consisted of comparisons of allele/genotype frequencies between patients and controls and within patient sub-groups according to BD clinical phenotypes and the presence of thyroid disorders. RESULTS: We found that the frequencies of the studied SNPs were similar in BD and HC groups. However, the CRP rs1130864 A allele carrier state was significantly more frequent: (i) in BD patients with thyroid disorders than in those without (pc = 0.046), especially among females (pc = 0.01) and independently of lithium treatment, (ii) in BD patients with rapid cycling than in those without (pc = 0.004). CONCLUSIONS: Overall, our findings suggest the possibility that CRP genetic diversity may contribute to the development of auto-immune comorbid disorders and rapid cycling, both proxy of BD severity. Such findings, if replicated, may allow to predict complex clinical presentations of the disease, a possible step towards precision medicine in psychiatry.
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BACKGROUND: Immunoproliferative small intestinal disease (also known as alpha chain disease) is a form of lymphoma that arises in small intestinal mucosa-associated lymphoid tissue (MALT) and is associated with the expression of a monotypic truncated immunoglobulin alpha heavy chain without an associated light chain. Early-stage disease responds to antibiotics, suggesting a bacterial origin. We attempted to identify a causative agent. METHODS: We performed polymerase chain reaction (PCR), DNA sequencing, fluorescence in situ hybridization, and immunohistochemical studies on intestinal-biopsy specimens from a series of patients with immunoproliferative small intestinal disease. RESULTS: Analysis of frozen intestinal tissue obtained from an index patient with immunoproliferative small intestinal disease who had a dramatic response to antibiotics revealed the presence of Campylobacter jejuni. A follow-up retrospective analysis of archival intestinal-biopsy specimens disclosed campylobacter species in four of six additional patients with immunoproliferative small intestinal disease. CONCLUSIONS: These results indicate that campylobacter and immunoproliferative small intestinal disease are associated and that C. jejuni should be added to the growing list of human pathogens responsible for immunoproliferative states.
Assuntos
Campylobacter jejuni/isolamento & purificação , Doença Imunoproliferativa do Intestino Delgado/microbiologia , Antibacterianos , Antiulcerosos/uso terapêutico , Infecções por Campylobacter , Campylobacter jejuni/genética , DNA Bacteriano/análise , Quimioterapia Combinada/uso terapêutico , Feminino , Genes de Imunoglobulinas , Humanos , Imunoglobulina A/sangue , Fragmentos de Imunoglobulinas/análise , Fragmentos de Imunoglobulinas/genética , Imuno-Histoquímica , Doença Imunoproliferativa do Intestino Delgado/tratamento farmacológico , Doença Imunoproliferativa do Intestino Delgado/patologia , Hibridização in Situ Fluorescente , Intestino Delgado/imunologia , Intestino Delgado/microbiologia , Intestino Delgado/patologia , Pessoa de Meia-Idade , Omeprazol/uso terapêutico , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
Nonorgan-specific autoantibodies (AAbs) are used for diagnosing autoimmune diseases but can also be detected in other conditions. We carried out a cross-sectional study with the aim to screen HIV1-infected patients in the era of highly active antiretroviral therapy (HAART) for AAbs and to analyze the association of their presence with hypergammaglobulinemia and immunovirological status.Blood samples from HIV1-infected patients without major concomitant illnesses followed in 2 hospitals in Paris, France were tested for immunovirological status, serum immunoglobulin G (IgG) level, antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), anti-extractable nuclear antigens (anti-ENAs), anticardiolipin (aCL), anti-ß2glycoprotein1 (anti-ß2GP1), and antineutrophil cytoplasmic antibodies (ANCAs). Clinically relevant AAbs were defined as ANAs with titers ≥1:160, anti-dsDNA or anti-ENA antibodies; aCL or anti-ß2GP1 antibodies with a level ≥40 U/ml; and ANCAs reacting with proteinase 3 or myeloperoxidase.We included 92 patients (mean age 47 years, men 55%, sub-Saharan African background 55%, HAART 85%, mean CD4 lymphocyte count 611/mm, viral loadâ<â40âcopies/mL 74%). At least 1 AAb was detected in 45% of patients, mostly ANAs (33%) and ANCAs (13%); 12% had ≥1 clinically relevant AAb. Above-normal IgG levels were found in 71% of patients. We found an inverse association between the presence of ≥1 AAb and CD4 lymphocyte count (Pâ=â0.03) and between above-normal IgG levels and duration of virological control (Pâ=â0.02) and non-sub-Saharan African background (Pâ=â0.001).In sum, in HIV1-infected patients without any major concomitant illness in the HAART era, the prevalence of AAbs remains high but AAb patterns leading to high suspicion of autoimmune diseases are rather uncommon. AAb presence is associated with reduced CD4 lymphocyte count but not hypergammaglobulinemia.
Assuntos
Terapia Antirretroviral de Alta Atividade , Autoanticorpos/sangue , Infecções por HIV/imunologia , Adulto , Estudos Transversais , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
IMPORTANCE: Chronic graft-vs-host-disease (cGVHD) after allogeneic stem cell transplantation (AHSCT) may resemble autoimmune diseases. Anti-MDA5 (melanoma differentiation-associated gene 5) dermatopulmonary syndrome is a subset of dermatomyositis defined by specific clinical features and detection of anti-MDA5-antibodies in the serum. OBJECTIVE: To characterize the clinical features of patients who underwent AHSCT and screened positively for anti-MDA5 antibodies. DESIGN, SETTING, AND PARTICIPANTS: For this monocentric retrospective study, we exained 81 patients screened for anti-MDA5 antibodies at a specific dermatological or pulmonary postallograft consultation between January 2014 to September 2015 at a National Reference Center; 2 additional patients not seen at this consultation but having clinical features suggestive of anti-MDA5 syndrome were included. Twenty serum samples from patients after AHSCT without cGVHD were used as controls. MAIN OUTCOMES AND MEASURES: Anti-MDA5 antibodies screened using an immunodot assay. RESULTS: Of 83 patients who underwent AHSCT (mean [SD] age, 47 [14] years), 6 patients tested positive for anti-MDA5 antibodies (mean [SD] age, 43 [16] years) including 4 patients with interstitial lung disease and 3 patients with cutaneous clinical features similar to anti-MDA5 skin symptoms encountered in patients who have not undergone AHSCT, namely finger pad inflammation, palmar violaceous papules, and digital ulcerations. Three patients had severe respiratory symptoms resistant to systemic steroids, and 1 patient died of severe interstitial lung disease. CONCLUSIONS AND RELEVANCE: The clinical features and long-term prognosis of patients who underwent AHSCT and test positively for anti-MDA5 antibodies should be evaluated in large prospective studies.
RESUMO
BACKGROUND: Genetic vulnerability to environmental stressors is yet to be clarified in bipolar disorder (BD), a complex multisystem disorder in which immune dysfunction and infectious insults seem to play a major role in the pathophysiology. Association between pattern-recognition receptor coding genes and BD had been previously reported. However, potential interactions with history of pathogen exposure are yet to be explored. METHODS: 138 BD patients and 167 healthy controls were tested for serostatus of Toxoplasma gondii, CMV, HSV-1 and HSV-2 and genotyped for TLR2 (rs4696480 and rs3804099), TLR4 (rs1927914 and rs11536891) and NOD2 (rs2066842) polymorphisms (SNPs). Both the pathogen-specific seroprevalence and the TLR/NOD2 genetic profiles were compared between patients and controls followed by modelling of interactions between these genes and environmental infectious factors in a regression analysis. RESULTS: First, here again we observed an association between BD and Toxoplasma gondii (p = 0.045; OR = 1.77; 95 % CI 1.01-3.10) extending the previously published data on a cohort of a relatively small number of patients (also included in the present sample). Second, we found a trend for an interaction between the TLR2 rs3804099 SNP and Toxoplasma gondii seropositivity in conferring BD risk (p = 0.017, uncorrected). CONCLUSIONS: Pathogen exposure may modulate the influence of the immunogenetic background on BD. A much larger sample size and information on period of pathogen exposure are needed in future gene-environment interaction studies.