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Mechanisms for the generation of anti-dsDNA autoantibodies are still not completely elucidated. One theory states that dsDNA interacts for mimicry with antibodies raised versus other antigens but molecular features for mimicry are unknown. Here we show that, at physiological acid-base balance, anti-Annexin A1 binds IgG2 dsDNA in a competitive and dose-dependent way with Annexin A1 and that the competition between the two molecules is null at pH 9. On the other hand, these findings also show that dsDNA and Annexin A1 interact with their respective antibodies on a strictly pH-dependent basis: in both cases, the binding was minimal at pH 4 and maximal at pH9-10. The anionic charge of dsDNA is mainly conferred by the numerous phosphatidic residues. The epitope binding site of Annexin A1 for anti-Annexin A1 IgG2 was here characterized as a string of 34 amino acids at the NH2 terminus, 10 of which are anionic. Circulating levels of anti-dsDNA and anti-Annexin A1 IgG2 antibodies were strongly correlated in patients with systemic lupus erythematosus (n 496) and lupus nephritis (n 425) stratified for age, sex, etc. These results show that dsDNA competes with Annexin A1 for the binding with anti-Annexin A1 IgG2 on a dose and charged mediated base, being able to display an inhibition up to 75%. This study provides the first demonstration that dsDNA may interact with antibodies raised versus other anionic molecules (anti-Annexin A1 IgG2) because of charge mimicry and this interaction may contribute to anti-dsDNA antibodies generation.
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Anexina A1 , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Anticorpos Antinucleares , Autoanticorpos , Imunoglobulina G , Anexina A1/metabolismo , DNARESUMO
Anti-double-stranded DNA antibodies (anti-dsDNA) are considered a specific marker for systemic lupus erythematosus (SLE). Though the Farr technique was once the reference method for their detection, it has been almost entirely replaced by more recently developed assays. However, there is still no solid evidence of the commutability of these methods in terms of diagnostic accuracy and their correlation with the Crithidia luciliae immunofluorescence test (CLIFT). Anti-dsDNA antibody levels were measured in 80 subjects: 24 patients with SLE, 36 disease controls drawn from different autoimmune rheumatic diseases (14 systemic sclerosis, 10 Sjögren's syndrome, nine autoimmune myositis, three mixed connective tissue disease), 10 inflammatory arthritis and 10 apparently healthy blood donors by eight different methods: fluorescence enzyme immunoassay, microdot array, chemiluminescent immunoassay (two assays), multiplex flow immunoassay, particle multi-analyte technology immunoassay and two CLIFT. At the recommended manufacturer cut-off, the sensitivity varied from 67% to 92%, while the specificity ranged from 84% to 98%. Positive agreement among CLIFT and the other assays was higher than negative agreement. Mean agreement among methods assessed by the Cohen's kappa was 0.715, ranging from moderate (0.588) to almost perfect (0.888). Evaluation of the concordance among quantitative values by regression analysis showed a poor correlation index (mean r2, 0.66). The present study shows that current technologies for anti-dsDNA antibody detection are not fully comparable. In particular, their different correlation with CLIFT influences their positioning in the diagnostic algorithm for SLE (either in association or sequentially). Considering the high intermethod variability, harmonization and commutability of anti-dsDNA antibody testing remains an unachieved goal.
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Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Síndrome de Sjogren , Humanos , Anticorpos Antinucleares , Lúpus Eritematoso Sistêmico/diagnósticoRESUMO
OBJECTIVES: We aimed to evaluate joint and vessel uptake in patients with polymyalgia rheumatica (PMR) by FDG-PET and correlate it with clinical findings. METHODS: Consecutive PMR patients, without clinical signs of giant cell arteritis, underwent a standardised clinical examination and FDG-PET/CT. Controls were consecutive subjects undergoing FDG-PET for the suspicion of neoplasm not confirmed by the examination. Uptake was evaluated by a qualitative visual score, using the liver uptake as reference and by the semi-quantitative mean standardised uptake value (SUV) and target-to-background ratio (TBR) methods. RESULTS: Eighty-four patients and 84 controls (55 women, median age 73 years, range 50-92 years in both groups) were studied. Sixteen patients were taking glucocorticoids (GC). PMR patients showed a higher articular uptake than controls. GC-treated patients showed uptake lower than GC-naïve patients, but still higher than controls. PMR patients showed a higher vascular uptake than controls in all districts except in the carotid arteries, when evaluated by the visual score. Conversely, the semi-quantitative approach yielded no significant differences. Forty-two patients (50%) showed PET evidence of large-vessel vasculitis (LVV), defined as uptake ≥ than that of the liver, and 11.9% showed LVV with vascular uptake higher than that of the liver. The correlation between clinical findings and uptake was scarce. Neither clinical nor laboratory findings could predict the presence of LVV. CONCLUSIONS: Patients with PMR show a typical joint pattern at FDG-PET. There are no clinical or laboratory predictors of LVV. Imaging appears to be the only tool to assess LVV in these patients.
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Arterite de Células Gigantes , Polimialgia Reumática , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Arterite de Células Gigantes/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Polimialgia Reumática/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos RadiofarmacêuticosRESUMO
PURPOSE OF REVIEW: Paraneoplastic neurological syndromes (PNS) are caused by nervous system-targeting aberrant anti-tumoral immune responses. We review the updated criteria for PNS diagnosis, incorporating novel information on clinical phenotypes, neuronal autoantibodies (Nabs), and tumors. The impact of the oncologic use of immune checkpoint inhibitors (ICI) on PNS occurrence is also addressed. RECENT FINDINGS: Clinical phenotypes and Nabs are redefined as "high/intermediate/low" risk, following the frequency of cancer association. Nabs, the diagnostic hallmark of PNS, can target intracellular or surface neuronal proteins, with important prognostic and pathogenic implications. Many novel assays have been incorporated into laboratory diagnostics, that is becoming increasingly complex. ICI fight tumors, but favor autoimmunity, thus increasing the incidence of PNS-like disorders. Overcoming the old PNS criteria, the new ones are centered around the presence of tumor. Clinical presentation, Nabs, and tumor findings are translated in diagnostic scores, providing a useful tool for PNS diagnosis and management.
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Neoplasias , Síndromes Paraneoplásicas do Sistema Nervoso , Autoanticorpos , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Neurônios , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , PrognósticoRESUMO
Clinical Trial registry name and registration number: Zeus study, NCT02403115.
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Nefropatias , Nefrite Lúpica , Humanos , Anticorpos , RimRESUMO
During coronavirus disease 2019 (COVID-19) pandemic, the early diagnosis of patients is a priority. Serological assays, in particular immunoglobulin (Ig)M and IgG anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have today several applications but the interpretation of their results remains an open challenge. Given the emerging role of the IgA isotype in the COVID-19 diagnostics, we aimed to identify the SARS-CoV-2 IgA antibodies in a COVID-19 population seronegative for IgM. A total of 30 patients hospitalized in San Giovanni di Dio Hospital (Florence, Italy) for COVID-19, seronegative for IgM antibodies, have been studied for anti-SARS-CoV-2 antibodies. They all had a positive oro/nasopharyngeal swab reverse transcription-polymerase chain reaction result. Assays used were a chemiluminescent assay measuring SARS-CoV-2 specific IgM and IgG (S + N) and an ELISA, measuring specific IgG (S1) and IgA antibodies against SARS-CoV-2. Among the 30 patients, eight were positive for IgA, seven were positive for IgG (N + S), and two for IgG (S1), at the first point (5-7 days from the onset of symptoms). The IgA antibodies mean values at the second (9-13 days) and third (21-25 days) time points were even more than twice as high as IgG assays. The agreement between the two IgG assays was moderate (Cohen's K = 0.59; SE = 0.13). The inclusion of the IgA antibodies determination among serological tests of the COVID-19 diagnostic is recommended. IgA antibodies may help to close the serological gap of the COVID-19. Variations among anti-SARS-CoV-2 IgG assays should be considered in the interpretation of results.
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Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19 , COVID-19/diagnóstico , Imunoglobulina A/sangue , SARS-CoV-2/imunologia , Adulto , Idoso , COVID-19/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoensaio , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis. METHODS: A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercial techniques. RESULTS: The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low-medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0-12 months), and high levels at T0-1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions. CONCLUSION: Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients. TRIAL REGISTRATION: The Zeus study was registered at https://clinicaltrials.gov, NCT02403115.
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Anticorpos Antinucleares/imunologia , Imunoglobulina G/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/imunologia , Adolescente , Adulto , Anexina A1/imunologia , Especificidade de Anticorpos , Síndrome Antifosfolipídica/imunologia , Artrite Reumatoide/imunologia , Biomarcadores Tumorais/imunologia , Complemento C1q/imunologia , Estudos Transversais , DNA/imunologia , Proteínas de Ligação a DNA/imunologia , Feminino , Histonas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Nucleossomos/imunologia , Fosfopiruvato Hidratase/imunologia , Proteínas Supressoras de Tumor/imunologia , Doenças do Tecido Conjuntivo Indiferenciado/imunologia , Adulto JovemRESUMO
OBJECTIVES: Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes. METHODS: Here we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques. RESULTS: LN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months. CONCLUSIONS: Anti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN. TRIAL REGISTRATION: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).
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Imunoglobulina G/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/imunologia , Adulto , Anexina A1/imunologia , Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , Biomarcadores Tumorais/imunologia , Complemento C1q/imunologia , DNA/imunologia , Proteínas de Ligação a DNA/imunologia , Progressão da Doença , Feminino , Histonas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Nucleossomos/imunologia , Fosfopiruvato Hidratase/imunologia , Estudos Prospectivos , Proteínas Supressoras de Tumor/imunologiaRESUMO
Although, the association between celiac disease (CD) and selective immunoglobulin A deficiency (SIgAD) has been known for more than fifty years, the procedures for diagnosing and monitoring patients with both conditions are still far from definitive. When serological markers were introduced as pre-bioptic investigations, it was immediately clear that searching for specific IgA antibodies without checking total serum IgA could lead to a failure in diagnosing IgA-deficient CD patients, while specific IgG antibodies could be useful as additional tests, because they are frequently found in the serum of affected patients. Nonetheless, until recently the diagnosis of CD in IgA-deficient patients was based on the few, fragmentary and often contradictory data available in literature. The introduction of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines in 2012 provided the current criteria for diagnosing CD in IgA-deficient patients, although some issues remained open, such as the selection of patients who should undergo specific IgG antibody testing and the choice of the most reliable IgG-based test for both diagnosis and follow-up. A real-life study recently assessed the impact of the 2012 ESPGHAN guidelines in diagnosing and monitoring CD in SIgAD patients, highlighting several pitfalls that can lead to operational uncertainties and difficulties in patient management. In the present report, the evolution of diagnostic tools and criteria for CD in SIgAD patients has been critically assessed, both strengths and open issues have been highlighted, and future perspectives for improving the current diagnostic protocols have been suggested.
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Doença Celíaca/diagnóstico , Doença Celíaca/genética , Deficiência de IgA/complicações , Imunoglobulina A/genética , Biomarcadores/sangue , Doença Celíaca/complicações , Humanos , Deficiência de IgA/diagnóstico , Imunoglobulina A/sangue , Guias de Prática Clínica como AssuntoRESUMO
INTRODUCTION: In the last years, many new drugs have been developed targeting different oncology pathways, overall improving both quality of life and survival in several malignancies. However, the increase of those therapies is associated with novel toxicities, mainly immune-related adverse events (irAEs), never observed before. Different irAEs are now well characterized, and, among them, neuromuscular complications, following immune checkpoint inhibitor (ICPi) therapy, are increasingly studied and described. However, there are also neurological complications related to the use of other targeted therapies, less known and probably underestimated. Herein we describe two oncological patients who developed neuromuscular diseases after administration of targeted therapies, different from ICPi. CASE REPORTS: The first patient was treated with the combination of Vemurafenib and Cobimetinib, BRAF and MEK inhibitors, respectively, for a cutaneous melanoma. One year after the beginning of the combined treatment, she developed a sub-acute motor neuropathy with predominant cranial nerve involvement. She was successfully treated with methylprednisolone. The second patient received therapy with Imatinib, tyrosine kinase inhibitor and precursor of the targeted therapy, for a gastrointestinal stromal tumour. Few days after the first administration, he developed generalized myasthenia gravis with respiratory failure. Clinical remission was obtained with plasma-exchange, intravenous immunoglobulins and steroids. DISCUSSION AND CONCLUSION: We strengthen the relevance of neuromuscular complications which may occur long after treatment start or in patients receiving not only the latest ICPi but also "older" and apparently better-known targeted therapies. Also in the latter cases, an immune-mediated "off-target" pathogenic mechanism can be hypothesized, and consequences can be life threatening, if not promptly diagnosed and appropriately managed.
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Melanoma , Miastenia Gravis , Neoplasias Cutâneas , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Masculino , Melanoma/tratamento farmacológico , Qualidade de VidaRESUMO
This document presents the guidelines for anti-ganglioside antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Main clinical information on dysimmune peripheral neuropathies, indications and limits of anti-ganglioside antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.
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Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso Periférico/diagnóstico , Anticorpos/metabolismo , Doenças Autoimunes do Sistema Nervoso/complicações , Gangliosídeos/imunologia , Humanos , Doenças do Sistema Nervoso Periférico/complicaçõesRESUMO
BACKGROUND: The use of automated immunometric methods for the detection of anti-thyroid peroxidase antibodies (TPOAb), the main serological marker of autoimmune thyroid diseases (AITD), has expanded in recent years. However, it is not known whether these new automated platforms have improved the diagnostic performance of TPOAb assays. The aim of this study was to evaluate the potential improvement of the inter-method agreement of current automated third generation systems, 12 years after a previous study, which had assessed the analytical variability between semi-automated second generation methods of TPOAb detection. METHODS: Eight pools of sera from patients with chronic lymphocytic thyroiditis, exhibiting different TPOAb concentrations, were collected from routine laboratory diagnostics and distributed to seven companies throughout Italy. All automated third generation methods were calibrated against the Medical Research Council (MRC) reference preparation 66/387. RESULTS: The overall mean variability (CV) was 93.6% when results were expressed in part as arbitrary Units (U/mL) and in part as International Units (IU/mL). The conversion of all values in IU/mL resulted in a significant decrease of CV (49.8%). The CV expressed as COM (cut-off concentration multiples) was 64.0%. Agreement of qualitative results was 95.3% with a pronounced difference in the threshold values proposed by manufacturers (range 3.2-35.0 IU/mL). CONCLUSIONS: These findings confirm the improvement of harmonisation between different methods of automated third generation TPOAb assays. Nevertheless, further efforts should be made in the definition of the positive cut-off concentration to avoid misclassification of AITD patients as well as in a new international reference preparation and in the autoantigen purification modality.
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Autoanticorpos/sangue , Autoanticorpos/imunologia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Imunoensaio/métodos , Iodeto Peroxidase/imunologia , Automação , Doença de Hashimoto/sangue , Doença de Hashimoto/enzimologia , HumanosRESUMO
Introduction: A potential overlap in symptoms between post-acute COVID-19 syndrome and post-COVID-19 vaccination syndrome has been noted. We report a paired description of patients presenting with similar manifestations involving the central (CNS) or peripheral nervous system (PNS) following SARS-CoV-2 infection or vaccination, suggesting that both may have triggered similar immune-mediated neurological disorders in the presence of anti-idiotype antibodies directed against the ACE2 protein. Patients and methods: Four patients exhibited overlapping neurological manifestations following SARS-CoV-2 infection or vaccination: radiculitis, Guillain-Barré syndrome, and MRI-negative myelitis, respectively, sharing positivity for anti-ACE2 antibodies. Autoantibodies against AQP-4, MOG, GlyR, GAD, and amphiphysin, onconeural antibodies for CNS syndromes, and anti-ganglioside antibodies for PNS syndromes tested negative in all patients. Discussion: Anti-idiotype antibodies against ACE2 have been detected in patients who recovered from COVID-19 infection, and it has been hypothesized that such antibodies may mediate adverse events following SARS-CoV-2 infection or vaccination, resulting in the activation of the immune system against cells expressing ACE2, such as neurons. Our data reveal clinically overlapping syndromes triggered by SARS-CoV-2 infection or vaccination, sharing positivity for anti-ACE2 antibodies. Their presence, in the absence of other classic autoimmune markers of CNS or PNS involvement, suggests that they might play an active role in the context of an aberrant immune response. Conclusion: Anti-idiotype antibodies directed against ACE2 may be triggered by both SARS-CoV-2 infection and vaccination, possibly contributing to neurological autoimmune manifestations. Their pathogenic role, however, remains to be demonstrated in large-scale, more structured studies.
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Enzima de Conversão de Angiotensina 2 , Autoanticorpos , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/imunologia , Masculino , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Autoanticorpos/imunologia , Autoanticorpos/sangue , Feminino , Enzima de Conversão de Angiotensina 2/imunologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Idoso , Anticorpos Anti-Idiotípicos/imunologia , Vacinação/efeitos adversos , Adulto , Síndrome de COVID-19 Pós-Aguda , Doenças do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/etiologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/etiologiaRESUMO
Classification criteria of autoimmune rheumatic diseases are an important means to define homogenous groups of patients that can be compared across studies for clinical trials and research purposes. The measurement of autoantibodies is a relevant aspect in the definition of classification criteria, with a significant weight in the scores necessary to classify patients with autoimmune rheumatic diseases. The impact of autoantibodies has gradually increased over the years, contributing to the evolution and improvement of the classification criteria. However, these criteria often do not take into consideration how autoantibodies are measured, i.e. differences in diagnostic accuracy of the methods. This is a critical point especially when obsolete analytical methods that are no longer used in many clinical laboratories are taken into consideration. In this review we have critically examined assays and methods for the determination of autoantibodies that are (or could be) included among the classification criteria of autoimmune rheumatic diseases in light of more recent evidence and technology evolution.
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Deposition of autoantibodies in glomeruli is a key factor in the development of lupus nephritis (LN). For a long time, anti-dsDNA and anti-C1q antibodies were thought to be the main cause of the kidney damage. However, recent studies have shown that the list of autoantibidies that have renal tropism and deposit in the kidney in LN is increasing and the link between anti-dsDNA and renal pathology is weak due to potential confounders. Aspecific bindings of dsDNA with cationic antibodies and of anti-dsDNA with several renal antigens such as actinin, laminin, entactin, and annexinA2 raised doubts about the specific target of these antibodies in the kidney. Moreover, the isotype of anti-dsDNA in SLE and LN has never received adequate interest until the recent observation that IgG2 are preponderant over IgG1, IgG3 and IgG4. Based on the above background, recent studies investigated the involvement of anti-dsDNA IgG2 and of other antibodies in LN. It was concluded that circulating anti-dsDNA IgG2 levels do not distinguish between LN versus non-renal SLE, and, in patients with LN, their levels do not change over time. Circulating levels of other antibodies such as anti-ENO1 and anti-H2 IgG2 were, instead, higher in LN vs non-renal SLE at the time of diagnosis and decreased following therapies. Finally, new classes of renal antibodies that potentially modify the anti-inflammatory response in the kidney are emerging as new co-actors in the pathogenetic scenario. They have been defined as 'second wave antibodies' for the link with detoxifying mechanisms limiting the oxidative stress in glomeruli that are classically stimulated in a second phase of inflammation. These findings have important clinical implications that may modify the laboratory approach to LN. Serum levels of anti-ENO1 and anti-H2 IgG2 should be measured in the follow up of patients for designing the length of therapies and identify those patients who respond to treatments. Anti-SOD2 could help to monitor and potentiate the anti-inflammatory response in the kidney.
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Autoanticorpos , Nefrite Lúpica , Nefrite Lúpica/imunologia , Nefrite Lúpica/diagnóstico , Humanos , Autoanticorpos/imunologia , Autoanticorpos/sangue , Animais , Anticorpos Antinucleares/imunologia , Anticorpos Antinucleares/sangue , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Autoantígenos/imunologiaRESUMO
BACKGROUND: Specific autoantibodies and nailfold videocapillaroscopy (NVC) findings are serum and morphological diagnostic hallmarks of systemic sclerosis (SSc) as well as useful biomarkers which stratify the microvascular progression and prognosis of patients. METHODS: The aim of our narrative review is to provide an update and overview of the link between SSc-related autoantibodies, used in clinical practice, and microvascular damage, evaluated by NVC, by exploring the interaction between these players in published studies. A narrative review was conducted by searching relevant keywords related to this field in Pubmed, Medline and EULAR/ACR conference abstracts with a focus on the findings published in the last 5 years. RESULTS: Our search yielded 13 clinical studies and 10 pre-clinical studies. Most of the clinical studies (8/13, 61.5%) reported a significant association between SSc-related autoantibodies and NVC patterns: more specifically anti-centromere autoantibodies (ACA) were associated more often with an "Early" NVC pattern, whereas anti-topoisomerase autoantibodies (ATA) more frequently showed an "Active" or "Late" NVC pattern. Five studies, instead, did not find a significant association between specific autoantibodies and NVC findings. Among the pre-clinical studies, SSc-related autoantibodies showed different mechanisms of damage towards both endothelial cells, fibroblasts and smooth muscle vascular cells. CONCLUSIONS: The clinical and laboratory evidence on SSc-related autoantibodies and microvascular damage shows that these players are interconnected. Further clinical and demographic factors (e.g., age, sex, disease duration, treatment and comorbidities) might play an additional role in the SSc-related microvascular injury whose progression appears to be complex and multifactorial.
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BACKGROUND: Autoimmune blistering diseases (AIBD), are a heterogeneous group. Despite their pathogenesis is not completely understood, autoantibodies against directed adhesion molecules of the skin and adjacent mucous membranes could play a key role. The leukocyte-associated-Ig-like-receptor (LAIR) family is a small group of immunoreceptor-tyrosine-based-inhibition-motif-containing inhibitory receptors, recognizing collagens. LAIR-1 is a transmembrane glycoprotein expressed on human-peripheral-blood-leukocytes. LAIR-2 is a secreted receptor mainly produced by CD4+ T-lymphocytes, and is able to regulate the inhibitory potential of LAIR-1. Both LAIRs have been associated with several autoimmune diseases and inflammatory responses. METHODS: We evaluated circulating LAIRs in patients with different blistering skin diseases by ELISA. RESULTS: A significant increase of serum LAIR-2, and to a lesser extent of sLAIR-1 (with the exception of Pemphigus vulgaris), in the whole group of patients with bullous diseases, irrespective of the pathogenesis, compared to healthy controls was evident. CONCLUSIONS: Although the pathophysiological meaning of LAIR is not completely elucidated, the presence of increased concentration of LAIR proteins can somehow modulate the cascade of inflammatory phenomenon occurring in bullous skin diseases, in different way depending upon specific skin disease considered.
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Receptores Imunológicos , Linfócitos T , Humanos , Receptores Imunológicos/metabolismo , Linfócitos T/metabolismo , Colágeno/metabolismo , Moléculas de Adesão Celular , Imunoglobulinas/metabolismoRESUMO
Drug-induced thrombocytopenia is an adverse reaction characterized by accelerated platelet destruction. The present study described a case of thrombocytopenia that occurred during treatment with panitumumab. A female patient aged 49 years with metastatic rectal adenocarcinoma was treated with 9 out of 12 cycles of therapy with the standard of care, 5-fluorouacil (5-FU), oxaliplatin and folic acid, in association with panitumumab. During cycle 10, the patient developed severe thrombocytopenia, so the therapy was adjusted to a lower dosage; however, during cycle 11, after administration of panitumumab and before administration of 5-FU or oxaliplatin, the patient again presented with severe thrombocytopenia, with a platelet count <2×109/l. Immunology test results were negative apart from anti-nucleus antibodies (titration, 1:160). Naranjo's algorithm was used to establish the relationship between the use of panitumumab and thrombocytopenia onset and a score of 6 ('probable') was found. The temporal link between the onset of symptoms and administration of therapy, the relapse of thrombocytopenia after re-administration of the drug during cycle 11 (positive rechallenge) and Naranjo score of 6 ('probable') are crucial elements for establishing the causal relationship and the probability that thrombocytopenia was related to the administration of panitumumab. The patient then underwent two cycles of therapy with 5-FU, folic acid and irinotecan, in association with bevacizumab, experiencing again the same adverse event. Treatment with monoclonal antibodies was suspended altogether in favor of a switch to trifluridine/tipiracil. No other serious adverse events were reported.
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Background: Several cases of adverse reactions following vaccination for coronavirus disease 2019 (COVID-19) with adenoviral vector vaccines or mRNA-based vaccines have been reported to date. The underlying syndrome has been named "vaccine-induced immune thrombotic thrombocytopenia" (VITT) or "thrombosis with thrombocytopenia syndrome (TTS)" with different clinical manifestations. Methods: We report the clinical course of five patients who had severe adverse reactions to COVID-19 vaccines, either with VITT/TTS, abdominal or pulmonary thrombosis after adenoviral vaccines, or Stevens' Johnson syndrome because of mRNA vaccination, all of whom required admission to the intensive care unit (ICU). Conclusions: All patients with severe or life-threatening suspected reaction to different types of COVID-19 vaccination required ICU admission. A prompt evaluation of early symptoms and individualized clinical management is needed to improve outcomes.