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Regardless of microbial virulence (i.e., the global infection-fatality ratio), age generally drives the prevalence of death from infection in unvaccinated humans. Four mortality patterns are recognized: the common U- and L-shaped curves of endemic infections and the unique W- and J-shaped curves of pandemic infections. We suggest that these patterns result from different sets of human genetic and immunological determinants. In this model, it is the interplay between (1) monogenic genotypes affecting immunity to primary infection that preferentially manifest early in life and related genotypes or their phenocopies, including auto-antibodies, which manifest later in life and (2) the occurrence and persistence of adaptive, acquired immunity to primary or cross-reactive infections, which shapes the age-dependent pattern of human deaths from infection.
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Doenças Transmissíveis , Humanos , Fatores Etários , Doenças Transmissíveis/mortalidade , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/epidemiologia , Imunidade Adaptativa/genética , Envelhecimento/imunologia , Envelhecimento/genética , PandemiasRESUMO
Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSAs/MAAs) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n = 558). Our PH cohort (n = 121) showed a significantly higher prevalence of overall weak positive MSAs/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p < 0.001). Notably, MSAs/MAAs were found in PH patients both with and without ILD, though more prevalent in those with ILD. Anti-synthetase and anti-overlap syndrome antibodies were the most common. Our study is the first to systematically show a high MSA/MAA prevalence in PH without IIM presentation. This highlights the need to consider PH when diagnosing MSA/MAA-associated conditions. We recommend MSA/MAA screening for newly diagnosed PH, especially in those with ILD, for early detection and potential immunomodulatory treatment. Further research should explore the link between MSAs/MAAs and PH, and the value of monitoring patients with weak MSA/MAA positivity over time.
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Objectives: This study aimed to investigate the first involved joints and associated factors in Turkish patients with rheumatoid arthritis (RA). Patients and methods: This retrospective cross-sectional study included 300 newly diagnosed and disease-modifying antirheumatic drug-naïve RA patients (240 females, 60 males; mean age: 54±1.2 years; range, 18 to 82 years). Baseline demographic, clinical, and laboratory data were evaluated between January 2022 and December 2022. The patients were divided into four groups according to autoantibody profile: antibody-negative patients (Group 1; both RF and anti-CCP were negative in this group of patients), RF-positive patients (Group 2), anti-CCP-positive patients (Group 3), and patients with dual seropositivity with RF and antiCCP (Group 4). The patients were also divided into two groups according to the size of the first affected joint: patients with SJI at diagnosis and patients without SJI involvement at diagnosis. Results: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody positivity rates were 40.3% and 35.6%, respectively. The mean lag time to diagnosis was 25±36 months. At the disease onset, 20% of patients did not have small joint involvement (SJI). Seronegative patients tended to be female (p=0.001), had longer lag time (p=0.001), and had lower levels of C-reactive protein (p=0.025), white blood count (p=0.005), and neutrophil/lymphocyte ratio (p=0.001) compared to the dual seropositive group. Patients presenting with SJI had a younger age (p=0.002), tended to be female (p=0.001), and had lower RF (p=0.034) and anti-CCP (p=0.031) positivity. Only age (p=0.005) and dual seronegativity (RF and anti-CCP; p=0.035) were the independent predictors of SJI in multivariate analysis. Conclusion: The decreasing age and seronegative status were defined as independent risk factors of SJI at the onset of RA. Population-based, prospective studies are needed for earlier diagnosis.
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A complex interaction among virulence factors, host-genes and host immune system is considered to be responsible for dengue virus (DENV) infection and disease progression. Generation of auto-antibodies during DENV infection is a major phenomenon that plays a role in the pathophysiology of dengue hemorrhagic fever and dengue shock syndrome. Hemostasis, thrombocytopenia, hepatic endothelial dysfunction, and autoimmune blistering skin disease (pemphigus) are different clinical manifestations of dengue pathogenesis; produced due to the molecular mimicry of DENV proteins with self-antigens like coagulation factors, platelets and endothelial cell proteins. This review elaborately describes the current advancements in auto-antibody-mediated immunopathogenesis which inhibits coagulation cascade and promotes hyperfibrinolysis. Auto-antibodies like anti-endothelial cell antibodies-mediated hepatic inflammation during severe DENV infection have also been discussed. Overall, this comprehensive review provides insight to target auto-antibodies that may act as potential biomarkers for disease severity, and a ground for the development of therapeutic strategy against DENV.
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Dengue , HumanosRESUMO
INTRODUCTION: Efgartigimod and ravulizumab, both approved for treating acetylcholine receptor auto-antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG), have not been directly compared. This paper assessed comparative effects of efgartigimod vs. ravulizumab for treating adults with AChR-Ab+ gMG using indirect treatment comparison methods. METHODS: The matching-adjusted indirect comparison used data from two randomized trials of adult men and women. The ADAPT (efgartigimod vs. placebo; individual patient data available) population was reweighted to match the CHAMPION (ravulizumab vs. placebo; index study; aggregate data available) population. The relative effect of efgartigimod versus placebo was estimated in this reweighted population and compared with the observed ravulizumab versus placebo effect to estimate the efgartigimod versus ravulizumab effect. The outcomes were Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG), and Myasthenia Gravis Quality of Life 15-item-revised scale (MG-QoL15r) assessed as cumulative effect (area under the curve; AUC) over 26 weeks (primary) and change from baseline at 4 weeks and time of best response (week 4 for efgartigimod; week 26 for ravulizumab). RESULTS: For MG-QoL15r, efgartigimod had a statistically significant improvement compared with ravulizumab over 26 weeks [mean difference (95% confidence interval): - 52.6 (- 103.0, - 2.3)], at week 4 [- 4.0 (- 6.6, - 1.4)], and at time of best response [- 3.9 (- 6.5, - 1.3)]. Efgartigimod had a statistically significant improvement over ravulizumab in MG-ADL at week 4 [- 1.9 (- 3.3, - 0.5)] and at time of best response [- 1.4 (- 2.8, 0.0)] and in QMG at week 4 [- 3.2 (- 5.2, - 1.2)] and at time of best response [- 3.0 (- 5.0, - 1.0)]. For AUC over 26 weeks, improvements were not significantly different between efgartigimod and ravulizumab for MG-ADL [- 8.7 (- 36.1, 18.8)] and QMG [- 13.7 (- 50.3, 22.9)]. CONCLUSION: Efgartigimod may provide a faster and greater improvement over 26 weeks in quality of life than ravulizumab in adults with AChR-Ab+ gMG. Efgartigimod showed faster improvements in MG-ADL and QMG than ravulizumab.
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Anticorpos Monoclonais Humanizados , Miastenia Gravis , Receptores Colinérgicos , Humanos , Miastenia Gravis/tratamento farmacológico , Masculino , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Pessoa de Meia-Idade , Receptores Colinérgicos/imunologia , Adulto , Autoanticorpos , Resultado do Tratamento , Idoso , Atividades Cotidianas , Qualidade de VidaRESUMO
Polycystic ovary syndrome (PCOS) is the leading cause of endocrine disorders among females of reproductive age and is linked with autoimmune disorders. PCOS has been associated with autoantibodies such as antinuclear antibody (ANA), anti-thyroid, and anti-Smith (anti-SM). Young patients with PCOS and systemic lupus erythematosus (SLE) have up to a 10-fold increase in stroke. We present a case of a patient with a history of PCOS (on metformin), hypothyroidism, and pulmonary embolism who presented to the emergency room with acute left-sided weakness. She was extensively investigated for risk factors and was eventually diagnosed with a cerebrovascular accident secondary to possible SLE with positive ANA (1:160, nuclear homogenous pattern). The diagnosis of PCOS, coupled with autoantibodies and recurring episodes of thromboembolic events, rendered her case management complex. She received tenecteplase and had thrombectomy done twice because of recurrent thrombotic events during her hospital stay. She passed away on the fifth day post-thrombectomy from a possible massive pulmonary embolism with hemodynamic compromise. There is a need for more research to comprehend the underlying mechanisms of SLE and PCOS to guide the proper management of patients in this situation.
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Serum antibodies to the autoantigen transglutaminase 2 (TG2) are increasingly harnessed to diagnose coeliac disease. Diagnostic guidelines for children give recommendation for a no-biopsy-based diagnosis through detection of high amounts of IgA anti-TG2 antibodies in serum with confirmation of positivity in a separate blood sample by characteristic autoantibody-staining of tissue. While measurement of IgA anti-TG2 also is important in the diagnostic workup of adults, the adult guidelines still mandate examination of gut biopsies. This requirement might well change in the future, as might the necessity for confirming autoantibody positivity by tissue staining. The key role of autoantibody serology for diagnosis of coeliac disease is paradoxical. Coeliac disease was considered, and still can be considered, a food intolerance disorder where autoantibodies at face value are out of place. The immunological mechanisms underlying the formation of autoantibodies in response to gluten exposure have been dissected. This review presents the current insights demonstrating that the autoantibodies in coeliac disease are intimately integrated in the maladapted immune response to gluten.
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Doença Celíaca , Hipersensibilidade Alimentar , Adulto , Criança , Humanos , Doença Celíaca/patologia , Transglutaminases , Autoanticorpos , Glutens/efeitos adversos , Imunoglobulina ARESUMO
BACKGROUND: Presence of autoantibodies against α-synuclein (α-syn AAb) in serum of the general population has been widely reported. That such peripheral factors may be involved in central nervous system pathophysiology was demonstrated by detection of immunoglobulins (IgGs) in cerebrospinal fluid and brain of Parkinson's disease (PD) patients. Thus, blood-borne IgGs may reach the brain parenchyma through an impaired blood-brain barrier (BBB). FINDINGS: The present study aims to evaluate the patho-physiological impact of α-syn AAbs on primary brain cells, i.e., on spontaneously active neurons and on astrocytes. Exposure of neuron-astrocyte co-cultures to human serum containing α-syn AAbs mediated a dose-dependent reduction of spontaneous neuronal activity, and subsequent neurodegeneration. Removal specifically of α-syn AAbs from the serum prevented neurotoxicity, while purified, commercial antibodies against α-syn mimicked the neurodegenerative effect. Mechanistically, we found a strong calcium flux into neurons preceding α-syn AAbs-induced cell death, specifically through NMDA receptors. NMDA receptor antagonists prevented neurodegeneration upon treatment with α-syn (auto)antibodies. α-syn (auto)antibodies did not affect astrocyte survival. However, in presence of α-syn, astrocytes reacted to α-syn antibodies by secretion of the chemokine RANTES. CONCLUSION: These findings provide a novel basis to explain how a combination of BBB impairment and infiltration of IgGs targeting synuclein may contribute to neurodegeneration in PD and argue for caution with α-syn immunization therapies for treatment of PD.
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Doença de Parkinson , alfa-Sinucleína , Humanos , alfa-Sinucleína/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Doença de Parkinson/metabolismo , Encéfalo/metabolismo , Neurônios/metabolismo , Imunoglobulinas/metabolismoRESUMO
Objective: This study aimed to study the relationship between auto-antibodies against apolipoprotein A1 (anti-apoA1 IgG), human immunodeficiency virus (HIV) infection, anti-retroviral therapy (ART), and the tryptophan pathways in HIV-related cardiovascular disease. Design: This case-control study conducted in South Africa consisted of control volunteers (n = 50), people living with HIV (PLWH) on ART (n = 50), and untreated PLWH (n = 44). Cardiovascular risk scores were determined, vascular measures were performed, and an extensive biochemical characterisation (routine, metabolomic, and inflammatory systemic profiles) was performed. Methods: Anti-apoA1 IgG levels were assessed by an in-house ELISA. Inflammatory biomarkers were measured with the Meso Scale Discovery® platform, and kynurenine pathway metabolites were assessed using targeted metabolomic profiling conducted by liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS). Results: Cardiovascular risk scores and vascular measures exhibited similarities across the three groups, while important differences were observed in systemic inflammatory and tryptophan pathways. Anti-apoA1 IgG seropositivity rates were 15%, 40%, and 70% in control volunteers, PLWH ART-treated, and PLWH ART-naïve, respectively. Circulating anti-apoA1 IgG levels were significantly negatively associated with CD4+ cell counts and positively associated with viremia and pro-inflammatory biomarkers (IFNγ, TNFα, MIPα, ICAM-1, VCAM-1). While circulating anti-apoA1 IgG levels were associated with increased levels of kynurenine in both control volunteers and PLWH, the kynurenine/tryptophan ratio was significantly increased in PLWH ART-treated. Conclusion: HIV infection increases the humoral response against apoA1, which is associated with established HIV severity criteria and kynurenine pathway activation.
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COVID-19 infection is a multi-system clinical disorder that was associated with increased morbidity and mortality. Even though antiviral therapies such as Remdesvir offered modest efficacy in reducing the mortality and morbidity, they were not efficacious in reducing the risk of future infections. So, FDA approved COVID-19 vaccines which are widely administered in the general population worldwide. These COVID-19 vaccines offered a safety net against future infections and re-infections. Most of these vaccines contain inactivated virus or spike protein mRNA that are primarily responsible for inducing innate and adaptive immunity. These vaccines were also formulated to contain supplementary adjuvants that are beneficial in boosting the immune response. During the pandemic, clinicians all over the world witnessed an uprise in the incidence and prevalence of cardiovascular diseases (COVID-Heart Syndrome) in patients with and without cardiovascular risk factors. Clinical researchers were not certain about the underlying reason for the upsurge of cardiovascular disorders with some blaming them on COVID-19 infections while others blaming them on COVID-19 vaccines. Based on the literature review, we hypothesize that adjuvants included in the COVID-19 vaccines are the real culprits for causation of cardiovascular disorders. Operation of various pathological signaling events under the influence of these adjuvants including autoimmunity, bystander effect, direct toxicity, anti-phospholipid syndrome (APS), anaphylaxis, hypersensitivity, genetic susceptibility, epitope spreading, and anti-idiotypic antibodies were partially responsible for stirring up the onset of cardiovascular disorders. With these mechanisms in place, a minor contribution from COVID-19 virus itself cannot be ruled out. With that being said, we strongly advocate for careful selection of vaccine adjuvants included in COVID-19 vaccines so that future adverse cardiac disorders can be averted.
Role of COVID-19 vaccines in casuation of cardiovascular diseases COVID-19 infection is a multi-system clinical disorder that was associated with increased morbidity and mortality. Even though antiviral therapies such as Remdesvir offered modest efficacy in reducing the mortality and morbidity, they were not efficacious in reducing the risk of future infections. So, FDA approved COVID-19 vaccines which are widely administered in the general population worldwide. These COVID-19 vaccines offered safety net against future infections and re-infections. Most of these vaccines contain inactivated virus or spike protein mRNA that are primary responsible for inducing innate and adaptive immunity. These vaccines were also formulated to contain supplementary adjuvants that are beneficial in boosting the immune response. During the pandemic, clinicians all over the world witnessed an uprise in the incidence and prevalence of cardiovascular diseases (COVID-Heart Syndrome) in patients with and without cardiovascular risk factors. Clinical researchers were not certain the underlying reason for upsurge of cardiovascular disorder with some blaming them on COVID-19 infections while others blaming them on COVID-19 vaccines. Based on the literature review, we hypothesize that adjuvants included in the COVID-19 vaccines the real culprits for causation of cardiovascular disorders. Operation of various pathological signaling events under the influence of these adjuvants including autoimmunity, bystander effect, direct toxicity, anti-phospholipid syndrome (APS), anaphylaxis, hypersensitivity, genetic susceptibility, epitope spreading, and anti-idiotypic antibodies were partially responsible for stirring up the onset of cardiovascular disorders. With these mechanisms in place, a minor contribution from COVID-19 virus itself cannot be ruled out. With that being said, we strongly advocate for careful selection of vaccine adjuvants included in COVID-19 vaccines so that future adverse cardiac disorders can be averted.
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In humans, the interindividual variability of clinical outcome following exposure to a microorganism is immense, ranging from silent infection to life-threatening disease. Age-specific immune responses partially account for the high incidence of infection during the first 28 days of life and the related high mortality at population level. However, the occurrence of life-threatening disease in individual newborns remains unexplained. By contrast, inborn errors of immunity and their immune phenocopies are increasingly being discovered in children and adults with life-threatening viral, bacterial, mycobacterial and fungal infections. There is a need for convergence between the fields of neonatal immunology, with its in-depth population-wide characterization of newborn-specific immune responses, and clinical immunology, with its investigations of infections in patients at the cellular and molecular levels, to facilitate identification of the mechanisms of susceptibility to infection in individual newborns and the design of novel preventive and therapeutic strategies.
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Imunidade , Micoses , Adulto , Criança , Humanos , Recém-Nascido , Fatores EtáriosRESUMO
Patients with decompensated liver cirrhosis, in particular those classified as Childs-Pugh class C, are at increased risk of severe coronavirus disease-2019 (COVID-19) upon infection with severe acute respiratory coronavirus 2 (SARS-CoV-2). The biological mechanisms underlying this are unknown. We aimed to examine the levels of serum intrinsic antiviral proteins as well as alterations in the innate antiviral immune response in patients with decompensated liver cirrhosis. Serum from 53 SARS-CoV-2 unexposed and unvaccinated individuals, with decompensated liver cirrhosis undergoing assessment for liver transplantation, were screened using SARS-CoV-2 pseudoparticle and SARS-CoV-2 virus assays. The ability of serum to inhibit interferon (IFN) signalling was assessed using a cell-based reporter assay. Severity of liver disease was assessed using two clinical scoring systems, the Child-Pugh class and the MELD-Na score. In the presence of serum from SARS-CoV-2 unexposed patients with decompensated liver cirrhosis there was no association between SARS-CoV-2 pseudoparticle infection or live SARS-CoV-2 virus infection and severity of liver disease. Type I IFNs are a key component of the innate antiviral response. Serum from patients with decompensated liver cirrhosis contained elevated levels of auto-antibodies capable of binding IFN-α2b compared to healthy controls. High MELD-Na scores were associated with the ability of these auto-antibodies to neutralize type I IFN signalling by IFN-α2b but not IFN-ß1a. Our results demonstrate that neutralizing auto-antibodies targeting IFN-α2b are increased in patients with high MELD-Na scores. The presence of neutralizing type I IFN-specific auto-antibodies may increase the likelihood of viral infections, including severe COVID-19, in patients with decompensated liver cirrhosis.
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COVID-19 , Interferon Tipo I , Hepatopatias , Transplante de Fígado , Humanos , Anticorpos , Cirrose HepáticaRESUMO
The process of glycation, characterized by the non-enzymatic reaction between sugars and free amino groups on biomolecules, is a key contributor to the development and progression of both microvascular and macrovascular complications associated with diabetes, particularly due to persistent hyperglycemia. This glycation process gives rise to advanced glycation end products (AGEs), which play a central role in the pathophysiology of diabetes complications, including nephropathy. The d-ribose-mediated glycation of fibrinogen plays a central role in the pathogenesis of diabetes nephropathy (DN) and retinopathy (DR) by the generation and accumulation of advanced glycation end products (AGEs). Glycated fibrinogen with d-ribose (Rb-gly-Fb) induces structural changes that trigger an autoimmune response by generating and exposing neoepitopes on fibrinogen molecules. The present research is designed to investigate the prevalence of autoantibodies against Rb-gly-Fb in individuals with type 2 diabetes mellitus (T2DM), DN & DR. Direct binding ELISA was used to test the binding affinity of autoantibodies from patients' sera against Rb-gly-Fb and competitive ELISA was used to confirm the direct binding findings by checking the bindings of isolated IgG against Rb-gly-Fb and its native conformer. In comparison to healthy subjects, 32% of T2DM, 67% of DN and 57.85% of DR patients' samples demonstrated a strong binding affinity towards Rb-gly-Fb. Both native and Rb-gly-Fb binding by healthy subjects (HS) sera were non-significant (p > 0.05). Furthermore, the early, intermediate, and end products of glycation have been assessed through biochemical and physicochemical analysis. The biochemical markers in the patient groups were also significant (p < 0.05) in comparison to the HS group. This study not only establishes the prevalence of autoantibodies against d-ribose glycated fibrinogen in DN but also highlights the potential of glycated fibrinogen as a biomarker for the detection of DN and/or DR. These insights may open new avenues for research into novel therapeutic strategies and the prevention of diabetes-related nephropathy and retinopathy.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Doenças Retinianas , Humanos , Nefropatias Diabéticas/complicações , Autoanticorpos , Ribose , Produtos Finais de Glicação Avançada/metabolismo , Fibrinogênio , Doenças Retinianas/complicaçõesRESUMO
BACKGROUND: Auto-antibodies neutralizing the activity of type I interferons have been recently described in patients infected by SARS-CoV-2. They can be present even before the onset of the infection. Since type I interferons exert a dichotomous role in the pathogenesis of acute versus chronic HIV infection and auto-antibodies are often found in untreated and anti-retroviral treated HIV+ patients, we investigated whether auto-antibodies anti-type I interferons are present at high prevalence in those HIV+ patients with concomitant opportunistic infections (OIs). METHODS: The analysis of auto-antibodies against two types of type I interferons (IFN-α2 and IFN-ω) was performed using the ELISA test in 60 patients chronically infected by HIV who showed concomitant infections caused by mycobacterium tuberculosis or nontuberculosis mycobacterium or with active cytomegalovirus infections. Results were compared with those of 283 SARS-CoV-2 swab positive patients showing mild to severe pneumonia. A chi-square (χ2 ) test or the Wilcoxon-Mann-Whitney test were used to compare the HIV+ patient categorical or continuous variables, respectively. RESULTS: A high prevalence of auto-antibodies to type I interferons was found in middle-aged HIV-infected patients with concomitant OIs (11.6% vs. 5.3% in COVID-19 subjects; p < .05). No statistically differences were found for viro/immunological characteristics (CD4 and CD8 cell counts and viral load) between patients with and without type I interferons auto-antibodies. CONCLUSIONS: This study, which is the first searching auto-antibodies against type I interferons in HIV-infected patients, demonstrated that their prevalence was higher than that expected by the age of these patients. Furthermore, it indicated that these auto-antibodies are nonspecifically increased in critical SARS-CoV-2 infection but can be found also in other infections.
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COVID-19 , Infecções por HIV , Interferon Tipo I , Pessoa de Meia-Idade , Humanos , Infecções por HIV/complicações , Estudos Transversais , COVID-19/epidemiologia , COVID-19/complicações , SARS-CoV-2 , AnticorposRESUMO
The presence of a certain group of auto-antibodies (AAbs) is known to correlate with the severity of COVID-19. It is, however, unknown if such AAbs are prevalent and impact COVID-19-related outcomes in lung transplant recipients (LTRs) who are immunosuppressed. We performed a retrospective study of LTRs with COVID-19 and analyzed samples before and after COVID-19 for IgG AAbs. AAbs analysis was carried out using autoimmune and coronavirus microarray and the resulting cross-sectional differences in Ab-scores and clinical variables were analyzed using Fischer's Exact test for categorical variables and a paired t-test for continuous variables. Linear regression was used to analyze the differences in Ab-scores and COVID-19 severity. LTRs with non-severe [NS gp (n = 10)], and severe [S gp (n = 8)] COVID-19 disease were included. Ferritin and acute respiratory failure were higher in the S group (p = 0.03; p < 0.0001). Among the AAbs analyzed, interferon-related AAbs (IFN-alpha2, IFN-beta, IFN lamba, IFN-epsilon), eight interleukin-related AAbs, and several tissue-related AAbs were also found to be changed significantly from pre- to post-COVID-19 (p < 0.05). IFN-lambda (p = 0.03) and IL-22 (p = 0.002) were significantly associated with COVID-19 severity and remained significant in linear regression analysis while controlling for other variables. AAbs are common in LTRs, and certain groups of antibodies are particularly enhanced in LTRs with severe COVID-19. Preliminary observations of this study need to be confirmed by a larger sample size.
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COVID-19 , Humanos , Autoimunidade , Estudos Retrospectivos , Transplantados , Estudos Transversais , Imunoglobulina G , PulmãoRESUMO
Bile acid synthesis disorders (BASD) are a group of rare autosomal recessive disorders. Of the nine different versions, BASD type 4 is characterized by a gene mutation in alpha-methylacyl-CoA racemase (AMACR), which is located on chromosome 5p13. These disorders generally present with a normal gamma-glutamyl transferase with cholestasis, absence of pruritis, and malabsorption of fat, which can lead to fat-soluble vitamin deficiencies. In adulthood, patients usually develop neurological sequelae. Initial testing can be done through the measurement of urine metabolites; however, confirmation of the diagnosis is achieved through whole exome sequencing. Treatment involves supplementation of oral cholic acid and modification of diet. Only 23 patients with this disease have been described. Here, we report two cases of siblings from a family in Bahrain with a novel AMACR mutation and a unique association with autoimmune antibodies alongside a literature review.
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Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are auto-antibodies to transglutaminase 2 (TG2) and transglutaminase 3 (TG3), respectively. DH patients have auto-antibodies reactive with both transglutaminase enzymes. Here it is reported that in DH both gut plasma cells and serum auto-antibodies are specific for either TG2 or TG3 with no TG2-TG3 cross reactivity. By generating monoclonal antibodies from TG3-specific duodenal plasma cells of DH patients, three conformational epitope groups are defined. Both TG2-specific and TG3-specific gut plasma cells have few immunoglobulin (Ig) mutations, and the two transglutaminase-reactive populations show distinct selection of certain heavy and light chain V-genes. Mass spectrometry analysis of TG3-specific serum IgA corroborates preferential usage of IGHV2-5 in combination with IGKV4-1. Collectively, these results demonstrate parallel induction of anti-TG2 and anti-TG3 auto-antibody responses involving separate B-cell populations in DH patients.
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Doença Celíaca , Dermatite Herpetiforme , Humanos , Imunoglobulina A , Plasmócitos , Proteína 2 Glutamina gama-Glutamiltransferase , TransglutaminasesRESUMO
Introduction: Malaria and Babesiosis are acute zoonotic disease that caused by infection with the parasite in the phylum Apicomplexa. Severe anemia and thrombocytopenia are the most common hematological complication of malaria and babesiosis. However, the mechanisms involved have not been elucidated, and only a few researches focus on the possible role of anti-erythrocyte and anti-platelet antibodies. Methods: In this study, the Plasmodium yoelii, P. chabaudi, Babesia microti and B. rodhaini infected SCID and ICR mice. The parasitemia, survival rate, platelet count, anti-platelet antibodies, and the level of IFN-γ and interleukin (IL) -10 was tested after infection. Furthermore, the P. yoelii, P. chabaudi, B. rodhaini and B. microti infected ICR mice were treated with artesunate and diminaze, the development of the anti-erythrocyte and anti-platelet antibodies in chronic stage were examined. At last, the murine red blood cell and platelet membrane proteins probed with auto-antibodies induced by P. yoelii, P. chabaudi, B. rodhaini, and B. microti infection were characterized by proteomic analysis. Results and discussion: The high anti-platelet and anti-erythrocyte antibodies were detected in ICR mice after P. yoelii, P. chabaudi, B. rodhaini, and B. microti infection. Actin of murine erythrocyte and platelet is a common auto-antigen in Plasmodium and Babesia spp. infected mice. Our findings indicate that anti-erythrocyte and anti-platelet autoantibodies contribute to thrombocytopenia and anemia associated with Plasmodium spp. and Babesia spp. infection. This study will help to understand the mechanisms of malaria and babesiosis-related thrombocytopenia and hemolytic anemia.
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Anemia Hemolítica , Babesiose , Malária , Plasmodium , Trombocitopenia , Camundongos , Animais , Babesiose/complicações , Babesiose/parasitologia , Camundongos Endogâmicos ICR , Proteômica , Camundongos SCID , Anticorpos , Eritrócitos/parasitologia , Malária/parasitologiaRESUMO
The nutritional status of pregnant women is considered to affect fetal development and the health condition of newborns, including their immune system. We investigated the relationship between the concentrations of magnesium (Mg), calcium (Ca), zinc (Zn), iron (Fe) and copper (Cu) in maternal serum (MS) and the concentrations of IgG antibodies and antineutrophil cytoplasmatic auto-antibodies against lactoferrin (Lf-ANCA) in umbilical cord serum (UCS). IgG was considered as a promoter of immunity, and Lf-ANCA as an inhibitor. The examined group consisted of 98 pregnant women and their healthy term newborn children. The concentrations of mineral elements were measured by FAAS/FAES, while the concentrations of antibodies were determined by ELISA. Excessive MS Fe and insufficient MS Cu were related to insufficient UCS IgG and excessive UCS Lf-ANCA. The correlation analysis showed confirming results. Adequate UCS IgG and Lf-ANCA were related to MS Mg at the strictly lower limit of the reference values. The results obtained seem to suggest that an excess of Fe and a deficiency of Cu in pregnancy may adversely affect some immune parameters of newborns. Reference values for MS Mg are likely to require reconsideration. It would be advisable to monitor the nutritional status of pregnant women with minerals in order to support the immune capacity of newborns.