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Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune diseases characterized by muscle involvement and various extramuscular manifestations. Interstitial lung disease (ILD) is one of the most common extramuscular manifestations of IIM and is associated with significant mortality and morbidity. The clinical phenotypes, treatment responses, and prognosis of IIM-ILD are significantly related to myositis-specific antibody (MSA) profiles, with some racial differences. The features associated with MSA in IIM-ILD could also be relevant to cases of ILD where MSA is present but does not meet the criteria for IIM. The anti-melanoma differentiation-associated gene 5 antibody is highly associated with rapidly progressive ILD (RP-ILD), especially in Asian populations, and with characteristic cutaneous manifestations, such as skin ulcers. Radiologically, ground-glass opacities, consolidations, and nonsegmental linear opacities were more predominant than reticular opacities and honeycombing. While the mortality rate is still around 30%, the prognosis can be improved with early intensive therapy with corticosteroids and multiple immunosuppressants. In contrast, anti-aminoacyl-tRNA synthetase (ARS) antibodies are associated with chronic ILD, although RP-ILD is also common. Patients with anti-ARS antibodies often show lung-predominant presentations, with subtle muscle and skin involvement. Radiologically, reticular opacities, with or without consolidation, are predominant and may progress to honeycombing over time. Combination therapy with corticosteroids and a single immunosuppressant is recommended to prevent relapses, which often lead to a decline in lung function and fatal long-term outcomes. Significant advances in immunology and genetics holds promise for fostering more personalized approaches to managing IIM-ILD.
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Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex etiology. Neutrophil extracellular traps (NETs are NETwork protein structures activated by neutrophils to induce the cleavage and release of DNA-protein complexes). Current studies have shown the critical involvement of NETs in the progression of autoimmune diseases, Neutrophils mostly gather in the inflammatory sites of patients and participate in the pathogenesis of autoimmune diseases in various ways. NETs, as the activated state of neutrophils, have attracted much attention in immune diseases. Many molecules released in NETs are targeted autoantigens in autoimmune diseases, such as histones, citrulline peptides, and myeloperoxidase. All of these suggest that NETs have a direct causal relationship between the production of autoantigens and autoimmune diseases. For RA in particular, as a disorder of the innate and adaptive immune response, the pathogenesis of RA is inseparable from the generation of RA. In this article, we investigate the emerging role of NETs in the pathogenesis of RA and suggest that NETs may be an important target for the treatment of inflammatory autoimmune diseases.
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Artritis Reumatoide , Progresión de la Enfermedad , Trampas Extracelulares , Neutrófilos , Trampas Extracelulares/inmunología , Trampas Extracelulares/metabolismo , Humanos , Artritis Reumatoide/inmunología , Artritis Reumatoide/metabolismo , Artritis Reumatoide/etiología , Artritis Reumatoide/patología , Neutrófilos/inmunología , Neutrófilos/metabolismo , Animales , Autoantígenos/inmunologíaRESUMEN
Intrahepatic cholangiocarcinoma (iCCA) presents a challenging diagnosis due to its nonspecific early clinical manifestations, often resulting in late-stage detection and high mortality. Diagnosing iCCA is further complicated by its limited accuracy, often necessitating multiple invasive procedures for precise identification. Despite carbohydrate antigen 19-9 (CA19-9) having been investigated and employed for iCCA diagnosis, it demonstrates modest diagnostic performance. Consequently, the identification of novel biomarkers with improved sensitivity and specificity remains an imperative yet formidable task. Autoantibodies, as early indicators of the immune response against cancer, offer a promising avenue for enhancing diagnostic accuracy. Our study aimed to identify non-invasive blood-based autoantibody biomarkers capable of distinguishing iCCA patients from healthy individuals (CTRs). We profiled autoantibodies in 26 serum samples (16 iCCAs and 10 CTRs) using protein microarrays containing 1622 functional proteins. Leveraging machine learning techniques, we identified a signature composed of three autoantibody biomarkers (NDE1, PYCR1, and VIM) in conjunction with CA19-9 for iCCA detection. This combined signature demonstrated superior diagnostic performance with an AUC of 96.9%, outperforming CA19-9 alone (AUC: 83.8%). These results suggest the potential of autoantibody biomarkers to develop a complementary non-invasive diagnostic utility for routine iCCA screening.
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Autoanticuerpos , Neoplasias de los Conductos Biliares , Biomarcadores de Tumor , Colangiocarcinoma , Humanos , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/inmunología , Colangiocarcinoma/sangre , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/inmunología , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/inmunología , Neoplasias de los Conductos Biliares/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Antígeno CA-19-9/sangre , Análisis por Matrices de Proteínas/métodosRESUMEN
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease caused by autoantibodies. Serum samples from patients with SLE (n = 10) were compared with those from normal controls (NCs, n = 5) using 21K protein chip analysis to identify a biomarker for SLE, revealing 63 SLE-specific autoantibodies. The anti-chaperonin-containing t-complex polypeptide-1 (TCP1) antibody exhibited higher expression in patients with SLE than in NCs. To validate the specificity of the anti-TCP1 antibody in SLE, dot blot analysis was conducted using sera from patients with SLE (n = 100), rheumatoid arthritis (RA; n = 25), Behçet's disease (BD; n = 28), and systemic sclerosis (SSc; n = 30) and NCs (n = 50). The results confirmed the detection of anti-TCP1 antibodies in 79 of 100 patients with SLE, with substantially elevated expression compared to both NCs and patients with other autoimmune diseases. We performed an enzyme-linked immunosorbent assay to determine the relative amounts of anti-TCP1 antibodies; markedly elevated anti-TCP1 antibody levels were detected in the sera of patients with SLE (50.1 ± 17.3 arbitrary unit (AU), n = 251) compared to those in NCs (33.9 ± 9.3 AU), RA (35 ± 8.7 AU), BD (37.5 ± 11.6 AU), and SSc (43 ± 11.9 AU). These data suggest that the anti-TCP1 antibody is a potential diagnostic biomarker for SLE.
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Autoanticuerpos , Biomarcadores , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/sangre , Biomarcadores/sangre , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Ensayo de Inmunoadsorción Enzimática/métodos , Estudios de Casos y ControlesRESUMEN
OBJECTIVE: To investigate differences in autoantibodies, clinical features, and long-term outcomes between juvenile-idiopathic inflammatory myopathy (IIM) and adult-IIM METHODS: Autoantibodies, clinical characteristics, and drug-free conditions for a maximum of 20 years were retrospectively analyzed in 320 Japanese IIM patients (juvenile-IIM, n = 34; adult-IIM, n = 286) using the Kyoto University Registry. RESULTS: Autoantibodies observed in juvenile-IIM were anti-TIF1-γ (15 %), anti-MDA-5 (15 %), anti-ARS (9 %), and anti-NXP-2 (6 %). Those observed in adult-IIM were anti-ARS (32 %), anti-MDA-5 (23 %), anti-TIF1-γ (8 %), anti-SRP (8 %), anti-Mi-2 (2 %), and anti-NXP-2 (1 %). The cumulative drug-free condition rate was higher in juvenile-IIM than in adult-IIM up to 20 years (juvenile-IIM vs. adult-IIM, 34 % vs. 18 %, p = 0.0016). Anti-TIF1-γ was associated with lesser muscle symptoms (60 % vs. 90 %), malignancy (0 % vs. 57 %), and glucocorticoid use (40 % vs. 86 %) in juvenile-IIM compared to adult-IIM, while juvenile-IIM more achieved drug-free conditions (60 % vs. 25 %). Both juvenile-IIM and adult-IIM with anti-MDA-5 demonstrated a high frequency of amyopathic dermatomyositis, interstitial lung disease (ILD), and multi-immunosuppressive therapy, with high drug-free conditions (50 % vs. 49 %). Both juvenile-IIM and adult-IIM with anti-ARS showed frequent skin rashes, muscle symptoms, and ILD, frequent need for multi-immunosuppressive therapy, and low drug-free condition rates (0 % vs. 3 %). Both juvenile-IIM and adult-IIM with anti-NXP-2 showed frequent skin rashes and muscle symptoms, low ILD frequency, and frequent use of methotrexate and glucocorticoids, which did not achieve drug-free conditions (0 % vs. 0 %). CONCLUSIONS: Drug-free condition was achieved more frequently in juvenile-IIM patients than adult-IIM patients. Specific autoantibodies were associated with different clinical characteristics and outcomes between juvenile-IIM and adult-IIM.
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Precise diagnostic biomarkers of anticitrullination protein antibody (ACPA)-negative and early-stage RA are still to be improved. We aimed to screen autoantibodies in ACPA-negative patients and evaluated their diagnostic performance. The human genome-wide protein arrays (HuProt arrays) were used to define specific autoantibodies from the sera of 182 RA patients and 261 disease and healthy controls. Statistical analysis was performed with SPSS 17.0. In Phase I study, 51 out of 19,275 recombinant proteins covering the whole human genome were selected. In Phase II validation study, anti-ANAPC15 (anaphase promoting complex subunit 15) exhibited 41.8% sensitivity and 91.5% specificity among total RA patients. There were five autoantibodies increased in ACPA-negative RA, including anti-ANAPC15, anti-LSP1, anti-APBB1, anti-parathymosin, and anti-UBL7. Anti-parathymosin showed the highest prevalence of 46.2% (p = 0.016) in ACPA-negative early stage (<2 years) RA. To further improve the diagnostic efficacy, a prediction model was constructed with 44 autoantibodies. With increased threshold for RA calling, the specificity of the model is 90.8%, while the sensitivity is 66.1% (87.8% in ACPA-positive RA and 23.8% in ACPA-negative RA) in independent testing patients. Therefore, HuProt arrays identified RA-associated autoantibodies that might become possible diagnostic markers, especially in early stage ACPA-negative RA.
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PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. CONCLUSION: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.
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Autoanticuerpos , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Nocardiosis , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Nocardiosis/inmunología , Nocardiosis/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Proteinosis Alveolar Pulmonar/inmunología , Proteinosis Alveolar Pulmonar/diagnóstico , Cryptococcus gattii/inmunologíaRESUMEN
Background: Patients suffering from neurological symptoms after COVID-19 vaccination (post-COVID-19 vaccination syndrome (PCVS)) have imposed an increasing challenge on medical practice, as diagnostic precision and therapeutic options are lacking. Underlying autoimmune dysfunctions, including autoantibodies, have been discussed in neurological disorders after SARS-CoV-2 infection and vaccination. Here, we describe the frequency and targets of autoantibodies against peripheral nervous system tissues in PCVS. Methods: Sera from 50 PCVS patients with peripheral neurological symptoms after COVID-19 vaccination and 35 vaccinated healthy controls were used in this study. IgG autoreactivity was measured via indirect immunofluorescence assays on mouse sciatic nerve teased fibers. The frequencies of autoantibodies were compared between groups using Fisher's exact test. Serum anti-ganglioside antibodies were measured in ganglioside blots. Autoantibody target identification was performed using immunoprecipitation coupled to mass spectrometry. Subsequent target confirmation was conducted via cell-based assays and ELISA. Results: Compared with controls, PCVS patients had a significantly greater frequency of autoantibodies against peripheral nervous system structures (9/50(18%) vs 1/35(3%); p=0.04). Autoantibodies bound to paranodes (n=5), axons (n=4), Schmidt-Lanterman incisures (n=2) and Schwann cell nuclei (n=1). Conversely, antibodies against gangliosides were absent in PCVS patients. Target identification and subsequent confirmation revealed various subunits of neurofilaments as well as DFS-70 as autoantibody epitopes. Conclusion: Our data suggest that autoantibodies against nervous system tissue could be relevant in PCVS patients. Autoantibodies against neurofilaments and cell nuclei with so far non-established links to this disease spectrum should be further elucidated to determine their biomarker potential.
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Autoanticuerpos , Vacunas contra la COVID-19 , COVID-19 , Inmunoglobulina G , SARS-CoV-2 , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Masculino , Femenino , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Persona de Mediana Edad , COVID-19/inmunología , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Anciano , Ratones , Animales , Adulto , Vacunación , Gangliósidos/inmunología , Nervios Periféricos/inmunologíaRESUMEN
Objective Patients with idiopathic interstitial pneumonia (IIP) often test positive for systemic scleroderma-specific autoantibodies (SSc-Ab), even if they do not meet the diagnostic criteria for systemic scleroderma (SSc). However, the significance of SSc-Ab in IIP is unknown. Methods We retrospectively studied the medical records of all patients suspected of interstitial lung disease (ILD) who visited our center between January 2016 and December 2021. We evaluated the association between SSc-Ab subtypes and clinical characteristics, prognosis, and incidence of acute exacerbation (AE) of IIP. Among 571 patients suspected of having IIP and SSc-Ab measured, we excluded cases with clear causes of ILD or those diagnosed with other diseases and analyzed 386 cases diagnosed as IIP. Results Among 386 IIP patients, 48 were SSc-Ab positive (platelet-derived growth factor receptor (PDGFR) in 0, Th/To in 10, anti-nucleolar organizer region 90 antibodies (NOR90) in 12, fibrillarin in five, RP155 in 14, RP11 in three, CENP A in seven, CENP B in 10, and Scl-70 in six). There was no significant difference in survival rate or incidence of AE between patients with or without SSc-Ab. Multivariate logistic regression analysis showed that age and malignancy were significant risk factors for death, whereas age, male sex, and anti-fibrillarin antibodies were significant risk factors for AE of IIP. Conclusion None of the SSc-Abs were associated with the risk of mortality, and anti-fibrillarin antibodies, along with age and male sex may contribute to the risk of AE of IIP, predicting severe lung involvement and warranting multidisciplinary treatment and careful follow-up.
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Multiple factors contribute to the development of connective tissue diseases (CTD), often alongside a range of interstitial lung diseases (ILD), including Sjögren's syndrome-associated ILD, systemic sclerosis-associated ILD, systemic lupus erythematosus-associated ILD, idiopathic inflammatory myositis-associated ILD. TRIM21(or Ro52), an E3 ubiquitin ligase, plays a vital role in managing innate and adaptive immunity, and maintaining cellular homeostasis, and is a focal target for autoantibodies in various rheumatic autoimmune diseases. However, the effectiveness of anti-TRIM21 antibodies in diagnosing CTD remains a matter of debate because of their non-specific nature. Recent studies indicate that TRIM21 and its autoantibody are involved in the pathogenesis of CTD-ILD and play an important role in diagnosis and prognosis. In this review, we focus on the contribution of TRIM21 in the pathogenesis of CTD-ILD, as well as the potential diagnostic value of its autoantibodies in different types of CTD-ILD for disease progression and potential as a novel therapeutic target.
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Autoanticuerpos , Enfermedades del Tejido Conjuntivo , Enfermedades Pulmonares Intersticiales , Ribonucleoproteínas , Humanos , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Ribonucleoproteínas/inmunología , Enfermedades del Tejido Conjuntivo/inmunología , Enfermedades del Tejido Conjuntivo/complicaciones , Autoanticuerpos/inmunología , Animales , BiomarcadoresRESUMEN
Background and Hypothesis: Environmental stressors may influence immune surveillance in B lymphocytes and stimulate autoimmune responses via epigenetic DNA methylation modifications in schizophrenia (SCZ). Study Design: A total of 2722, Chinese Han origin subjects were recruited in this study (2005-2011), which included a discovery follow-up cohort with 40 remitters of SCZ (RSCZ), 40 nonremitters of SCZ (NRSCZ), and 40 controls (CTL), and a replication follow-up cohort (64 RSCZ, 16 NRSCZ, and 84 CTL), as well as a case-control validation cohort (1230 SCZ and 1208 CTL). Genomic DNA methylation, target gene mRNA transcripts, and plasma autoantibody levels were measured across cohorts. Study Results: We found extensive differences in global DNA methylation profiles between RSCZ and NRSCZ groups, wherein differential methylation sites (DMS) were enriched with immune cell maturation and activation in the RSCZ group. Out of 2722 participants, the foremost DMS cg14341177 was hyper-methylated in the SCZ group and it inhibited the alternative splicing of its target gene BICD2 and may have increased its autoantigen exposure, leading to an increase in plasma anti-BICD2 IgG antibody levels. The levels of cg14341177 methylation and anti-BICD2 IgG decreased significantly in RSCZ endpoint samples but not in NRSCZ endpoint samples. There are strong positive correlations between cg14341177 methylation, anti-BICD2 IgG, and positive and negative syndrome scale (PANSS) scores in the RSCZ groups, but not in the NRSCZ groups. Conclusions: These data suggest that abnormal DNA methylation could affect autoreactive responses in SCZ, and that cg14341177 methylation and anti-BICD2 IgG levels may potentially serve as useful biomarkers.
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The most characteristic feature of membranous nephropathy (MN) is the presence of subepithelial electron dense deposits and the consequential thickening of the glomerular basement membrane. There have been great advances in the understanding of the destiny of immune complexes in MN by the benefit of experimental models represented by Heymann nephritis. Subepithelial immune complexes are formed in situ by autoantibodies targeting native autoantigens or exogenous planted antigens such as the phospholipase A2 receptor (PLA2R) and cationic BSA respectively. The nascent immune complexes would not be pathogenic until they develop into immune deposits. Podocytes are the major source of autoantigens in idiopathic membranous nephropathy. They also participate in the modulation and removal of the immune complexes to a large extent. The balance between deposition and clearance is regulated by a wide range of factors such as the composition and physicochemical properties of the immune complexes and the complement system. Complement components such as C3 and C1q have been reported to be precipitated with the deposits whereas a complement regulatory protein CR1 expressed by podocytes is involved in the phagocytosis of immune complexes by podocytes. Podocytes regulate the dynamic change of immune complexes which is disturbed in membranous nephropathy. To elucidate the precise fate of the immune complexes is essential for developing more rational and novel therapies for membranous nephropathy.
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Complejo Antígeno-Anticuerpo , Glomerulonefritis Membranosa , Podocitos , Glomerulonefritis Membranosa/inmunología , Humanos , Complejo Antígeno-Anticuerpo/inmunología , Complejo Antígeno-Anticuerpo/metabolismo , Podocitos/inmunología , Podocitos/metabolismo , Animales , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Receptores de Fosfolipasa A2/inmunologíaRESUMEN
INTRODUCTION: Screening for islet-specific autoantibodies can identify individuals at risk for type 1 diabetes (T1D). Despite calls for increased nationwide autoantibody screening efforts, it is unclear how many individuals have participated in screening among people who may benefit from it. Moreover, knowledge and perceptions of autoantibody screening in real-world samples are not well understood. METHODS: We surveyed a sample of individuals (aged 18+ years old) from T1D Exchange Registry with a personal or family history of T1D to assess their self-reported T1D autoantibody knowledge, experiences, and attitudes. Participants belonged to one of three groups: adults with T1D who had a biological child without T1D or future plans for a child (PWD); parents without T1D who had a biological child with T1D and one or more biological children without T1D (Caregivers); and first-degree adult children or siblings to a person with T1D (Relatives). Descriptive analyses (means, standard deviations, frequencies) are presented by participant groups. RESULTS: A total of 510 participants enrolled in the study. Across groups, participants reported feeling a little to somewhat knowledgeable about autoantibody screening and positive perceptions of autoantibody screening in general. However, few participants had screened their child without T1D (PWDs, 21.94%; Caregivers, 46.30%) or themselves (Relatives, 19.23%). Among those who had screened, participants reported generally positive experiences. Among those who had not screened, many participants were "undecided" about autoantibody screening (PWD, 38.46%; Caregivers, 40.52%; Relatives, 44.44%). Influences reported for participants' decisions to screen, not screen, or their current indecision differed by group: PWDs (21.70%) and Caregivers (26.87%) most often reported self-initiated research as an influence and Relatives reported they had not previously considered screening (48.28%). CONCLUSION: Results highlight the need for more accessible information about screening, including real experiences from those who have screened.
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The autoimmune channelopathies represent a rapidly evolving scientific and clinical domain. The description of channels, expressed on neurons and glia, as targets of autoantibodies in neuromyelitis optica, autoimmune encephalitis, and related syndromes have revolutionized many areas of neurologic practice. To date, tens of surface antibody specificities have been described, a number that is likely to continue to increase. A central paradigm for all these disorders is that of pathogenic autoantibodies which target extracellular epitopes accessible for binding in vivo. Hence, in these disorders, the autoantibodies are causative diagnostic tools, and provide valuable reagents to model the diseases. Their production by B-lineage cells provides opportunities to study and modulate their production. Across these syndromes, early recognition and treatment are critical since most respond to immunotherapies. Yet, several unmet medical needs persist within treated patient populations, and widespread clinical under-recognition remains a challenge. In this review, we summarize the neuroscience and immunologic basis of autoantibody-mediated central nervous system channelopathies, the molecular effects of the autoantibodies, clinical phenotypes, and treatment approaches. We describe progress since the inauguration of the field through to open questions and potential future directions.
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Autoanticuerpos , Canalopatías , Humanos , Autoanticuerpos/inmunología , Canalopatías/inmunología , AnimalesRESUMEN
A 32-year-old male presented with unilateral orbital-temporal pulsatile headache, followed by fever in the 38°C range and nausea. The patient experienced two episodes of transient dysarthria and tinnitus, each lasting several minutes. MRI revealed swelling of the left cerebral cortex, enhancement of the leptomeninges, dilation of the left middle cerebral artery, and subcortical FLAIR hypointensity. The clinical presentation and MRI findings raised suspicions of myelin oligodendrocyte glycoprotein (MOG) antibody-associated cortical encephalitis. After two courses of steroid pulse therapy, the patient's headache subsided, and there was a significant improvement in the swelling of the left cerebral cortex. Subsequently, serum MOG antibody positivity was confirmed. While unilateral cortical FLAIR hyperintensity and increased blood flow can be observed in various diseases, MOG antibody-associated cortical encephalitis is notably characterized by subcortical FLAIR hypointensity, a finding more frequently observed in this condition compared to other diseases. In this case, the findings were useful for early diagnosis and intervention.
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Post-transplant diabetes mellitus (PTDM) is a well-known solid organ transplant complication, which can be related to immunosuppressants, particularly tacrolimus. We report an unusual presentation of PTDM with diabetic ketoacidosis (DKA). This is unique as PTDM typically resembles Type 2 DM, whereas DKA is associated with Type 1 DM and has rarely been reported as a complication of tacrolimus. A 38-year-old African American male on LCP-tacrolimus presented four months post kidney transplant with vomiting, weakness, poor appetite, and polyuria. Labs demonstrated hyperglycemia, ketonuria, and high anion gap metabolic acidosis. He was nonobese and had no personal or family history of Type 2 DM. DKA was suspected to be secondary to tacrolimus-induced pancreatic beta cell damage worsened by supratherapeutic tacrolimus levels. Latent autoimmune diabetes in adults (LADA) was diagnosed when further testing showed insulinopenia, low C-peptide, and anti-glutamic acid decarboxylase (GAD) autoantibodies. He required 120-units of subcutaneous insulin daily. Our literature review revealed only 16 other tacrolimus-induced DKA cases. No cases reported anti-GAD positivity and most showed beta cell toxicity reversibility with tacrolimus tapering or substitution. Our patient was early post-transplant with leukocytopenia, so tacrolimus was not exchanged. This unusual PTDM case may have resulted from both autoimmune and tacrolimus-induced beta cell destruction. Physicians should be aware of new onset LADA post-transplantation and tacrolimus toxicity leading to DKA, even in patients without traditional risk factors. Anti-GAD antibody screening in patients on tacrolimus who develop PTDM may identify patients less likely to recover beta cell function with immunosuppression augmentation which requires careful monitoring.
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BACKGROUND: Inclusion body myositis (IBM) is a progressive myopathy occurring in patients over 45 years of age, with heterogeneous and variable clinical features. This study aimed to determine the influence of autoantibodies, gender, and age of onset on the clinical features of IBM. METHODS: Medical records and muscle histology findings of 570 participants with suspected IBM were reviewed. Various characteristics of patients who met the 2011 ENMC IBM diagnostic criteria were compared based on the presence of anti-cytosolic 5'-nucleotidase 1 A (cN1A) autoantibodies, gender, age of onset, and disease duration. RESULTS: Of the 353 patients who met the criteria, 41.6% were female. The mean age at onset was 64.6 ± 9.3 years, and the mean duration from onset to diagnosis was 5.7 ± 4.7 years. 196 of the 353 patients (55.5%) were positive for anti-cN1A autoantibodies and 157 were negative. Logistic regression showed that patients with anti-cN1A autoantibodies had a higher frequency of finger flexion weakness. Multiple regression showed that patients with later age of onset had shorter disease duration, lower BMI, and lower serum CK levels. Male patients had a higher frequency of onset with finger weakness and female patients had a lower BMI. CONCLUSION: Autoantibodies, gender, age of onset, and disease duration may influence the clinical presentation of IBM, highlighting the need for a precision medicine approach that considers these factors along with the underlying mechanisms of the disease.
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5'-Nucleotidasa , Edad de Inicio , Autoanticuerpos , Miositis por Cuerpos de Inclusión , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , 5'-Nucleotidasa/inmunología , Autoanticuerpos/sangre , Miositis por Cuerpos de Inclusión/inmunología , Miositis por Cuerpos de Inclusión/sangre , Miositis por Cuerpos de Inclusión/diagnóstico , Estudios Retrospectivos , Caracteres SexualesRESUMEN
Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy was described for the first time in 2016. The most common clinical manifestation is meningoencephalomyelitis associated with a characteristic imaging pattern that allows diagnostic suspicion and its confirmation through determination of antibodies in serum and cerebrospinal fluid (CSF). We present a case of a 35-year-old patient with involvement of the central and peripheral nervous system and a recent diagnosis of thyroid cancer, which compared to the compatible clinical picture of meningoencephalomyelitis, characteristic findings on MRI and after the exclusion of alternative pathologies, we finally arrived at the diagnosis by the positive determination of anti-GFAP in CSF. The patient underwent surgical treatment and radioactive iodine for the diagnosed thyroid tumor and she subsequently received treatment with corticosteroids with partial improvement of the neurological symptomatology. We emphasize that in this pathology the MRI images usually depict a characteristic pattern, although not pathognomonic, it is necessary to consider other causes. Before a high suspicion of this entity due to the clinical and imaging picture, it is convenient to measure the antibody in CSF, given the greater sensitivity and specificity compared to its serum screening, in order to arrive to the definitive etiological diagnosis as it was done in the clinical case that is presented.
La astrocitopatía autoinmune asociada a proteína ácida fibrilar glial (GFAP) fue descripta por primera vez en el año 2016. La manifestación clínica más frecuente es la meningoencefalomielitis asociado a un patrón imagenológico característico que permite la sospecha diagnóstica y su confirmación mediante la determinación de los anticuerpos en suero y en líquido cefalorraquídeo (LCR). Presentamos el caso de una paciente de 35 años con compromiso del sistema nervioso a nivel central y periférico y un reciente diagnóstico de cáncer de tiroides, que frente al cuadro clínico compatible de meningoencefalomielitis, los hallazgos característicos en resonancia magnética y luego de la exclusión de enfermedades alternativas, finalmente se arribó al diagnóstico por la determinación positiva de anti GFAP en LCR. Realizó tratamiento quirúrgico y con iodo radioactivo por su tumor hallado y posteriormente recibió tratamiento con corticoides con mejoría parcial de la signo-sintomatología neurológica. Destacamos que en esta enfermedad las imágenes por resonancia magnética presentan un patrón característico, aunque no patognomónico, siendo necesario considerar otras causas. Ante una alta sospecha de esta entidad por el cuadro clínico e imagenológico, es conveniente realizar dosaje del anticuerpo en LCR, dada la mayor sensibilidad y especificidad en comparación con su pesquisa en suero, con el fin de arribar al diagnóstico etiológico definitivo como en el caso clínico presentado.
Asunto(s)
Proteína Ácida Fibrilar de la Glía , Imagen por Resonancia Magnética , Adulto , Femenino , Humanos , Astrocitos/patología , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico por imagen , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Proteína Ácida Fibrilar de la Glía/sangre , Proteína Ácida Fibrilar de la Glía/inmunologíaRESUMEN
Autoantibody binding has a central role in autoimmune diseases and has also been linked to cancer, infections, and behavioral disorders. Autoimmune neurological diseases remain misclassified also due to an incomplete understanding of the underlying disease-specific epitopes. Such epitopes are crucial for both pathology and diagnosis, but have historically been overlooked. Recent technological advancements have enabled the exploration of these epitopes, potentially opening novel clinical avenues. The precise identification of novel B and T cell epitopes and their autoreactivity has led to the discovery of autoantigen-specific biomarkers for patients at high risk of autoimmune neurological diseases. In this review, we propose utilizing newly available synthetic and cellular-surface display technologies and guide epitope-focused studies to unlock the potential of disease-specific epitopes for improving diagnosis and treatments. Additionally, we offer recommendations to guide emerging epitope-focused studies to broaden the current landscape.