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1.
Clin Immunol ; 210: 108269, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31683054

RESUMO

Genetic studies have led to identification of an increasing number of monogenic primary immunodeficiency disorders. Monoallelic pathogenic gain-of-function (GOF) variants in NFKBIA, the gene encoding IκBα, result in an immunodeficiency disorder, typically accompanied by anhidrotic ectodermal dysplasia (EDA). So far, 14 patients with immunodeficiency due to NFKBIA GOF mutations have been reported. In this study we report three patients from the same family with immunodeficiency, presenting with recurrent respiratory tract infections, bronchiectasis and viral skin conditions due to a novel pathogenic NFKBIA variant (c.106 T > G, p.Ser36Ala), which results in reduced IκBα degradation. Immunological investigations revealed inadequate antibody responses against vaccine antigens, despite hypergammaglobulinemia. Interestingly, none of the studied patients displayed features of EDA. Therefore, missense NFKBIA variants substituting serine 36 of IκBα, differ from the rest of pathogenic GOF NFKBIA variants in that they cause combined immunodeficiency, even in the absence of EDA.

2.
Front Immunol ; 10: 2618, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803180

RESUMO

Adult-onset primary immunodeficiency is characterized by recurrent infections, hypogammaglobulinemia, and poor antibody response to vaccines. In this study, we have analyzed targeted gene panel sequencing results of 270 patients diagnosed with antibody deficiency and identified five disease-associated variants in NFKB1 in five unrelated families. We detected two single base pair deletions and two single base pair insertions, causing severe protein truncations, and one missense mutation. Immunoblotting, lymphocyte stimulation, immunophenotyping, and ectopic expression assays demonstrated the functional relevance of NFKB1 mutations. Besides antibody deficiency, clinical manifestations included infections, autoimmune features, lymphoproliferation, lymphoma, Addison's disease, type 2 diabetes and asthma. Although partial clinical penetrance was observed in almost all pedigrees, all carriers presented a deficiency in certain serum immunoglobulins and the majority showed a lack of memory B cells (CD19+CD27+). Among all tested genes, NFKB1 alterations were the most common monoallelic cause of antibody deficiency in our cohort.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31718046

RESUMO

: Background: Currently, half of the population displaced worldwide is children and adolescents. Little is known on healthcare demand in underage migrants. MATERIALS AND METHODS: We analyzed healthcare utilization in n = 1.411 children and adolescents living in a large German refugee reception in 2015-2016. RESULTS: The mean age of all included refugees was 9 years (60.8% male). The majority came from the eastern Mediterranean region. During a mean camp inhabitance of 34 days, 57.6% needed primary healthcare, with a significant inverse correlation of healthcare seeking frequency with age and duration of camp inhabitance. Infants and unaccompanied minors displayed particular high demands for medical help. DISCUSSION: Our analysis showed that pediatric primary healthcare in pediatric and adolescent refugees are most sought during the first period upon arrival with particular demand in infants, toddlers, and unaccompanied minors. Based on this data, future care taking strategies should be adapted accordingly.

4.
Stem Cell Reports ; 13(4): 590-598, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31543470

RESUMO

Mutations in the NADPH oxidase, which is crucial for the respiratory burst in phagocytes, result in chronic granulomatous disease (CGD). The only curative treatment option for CGD patients, who suffer from severe infections, is allogeneic bone marrow transplantation. Over 90% of patients with mutations in the p47phox subunit of the oxidase complex carry the deletion c.75_76delGT (ΔGT). This frequent mutation most likely originates via gene conversion from one of the two pseudogenes NCF1B or NCF1C, which are highly homologous to NCF1 (encodes p47phox) but carry the ΔGT mutation. We applied CRISPR/Cas9 to generate patient-like p47-ΔGT iPSCs for disease modeling. To avoid unpredictable chromosomal rearrangements by CRISPR/Cas9-mediated cleavage in the pseudogenes, we developed a gene-correction approach to specifically target NCF1 but leave the pseudogenes intact. Functional assays revealed restored NADPH oxidase activity and killing of bacteria in corrected phagocytes as well as the specificity of this approach.

5.
Front Immunol ; 10: 1272, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379802

RESUMO

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.

6.
J Immunol ; 203(4): 795-800, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31292215

RESUMO

Protein arginine deiminase (PAD) enzymes catalyze the conversion of protein-bound arginine into citrulline, an irreversible posttranslational modification with loss of a positive charge that can influence protein-protein interactions and protein structure. Protein arginine deiminase activity depends on high intracellular calcium concentrations occurring in dying cells. In this study, we demonstrate that protein citrullination is common during pyroptotic cell death in macrophages and that inhibition of PAD enzyme activity by Cl-amidine, a pan-PAD inhibitor, blocks NLRP3 inflammasome assembly and proinflammatory IL-1ß release in macrophages. Genetic deficiency of either PAD2 or PAD4 alone in murine macrophages does not impair IL-1ß release; however, pharmacological inhibition or small interfering RNA knockdown of PAD2 within PAD4-/- macrophages does. Our results suggest that PAD2 and 4 activity in macrophages is required for optimal inflammasome assembly and IL-1ß release, a finding of importance for autoimmune diseases and inflammation.

7.
Diseases ; 7(2)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987377

RESUMO

Immunodeficiency, centromeric instability and facial anomalies syndrome 2 (ICF2) is a rare autosomal recessive primary immunodeficiency disorder. So far, 27 patients have been reported. Here, we present three siblings with ICF2 due to a homozygous ZBTB24 gene mutation (c.1222 T>G, p. (Cys408Gly)). Immune deficiency in these patients ranged from late-onset combined immunodeficiency (CID) with severe respiratory tract infections and recurrent shingles to asymptomatic selective antibody deficiency. Evident clinical heterogeneity manifested despite a common genetic background, suggesting the pathogenic relevance of epigenetic modification. Immunological follow-up reveals a previously unidentified gradual depletion of B and CD4⁺ T cells in all three presented patients with transition of a common variable immunodeficiency (CVID)-like disease to late-onset-CID in one of them. Considering all previously published cases with ICF2, we identify inadequate antibody responses to vaccines and reduction in CD27⁺ memory B cells as prevalent immunological traits. High mortality among ICF2 patients (20%) together with the progressive course of immunodeficiency suggest that hematopoietic stem cell transplantation (HSCT) should be considered as a treatment option in due time.

8.
Arthritis Rheumatol ; 71(5): 729-735, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30418704

RESUMO

OBJECTIVE: Autoantibodies against CD74 (anti-CD74) are associated with ankylosing spondylitis (AS). The present multicenter study, the International Spondyloarthritis Autoantibody (InterSpA) trial, was undertaken to compare the sensitivity and specificity of anti-CD74 and HLA-B27 in identifying patients with nonradiographic axial spondyloarthritis (axSpA). METHODS: Patients ages 18-45 years with inflammatory back pain of ≤2 years' duration and a clinical suspicion of axSpA were recruited. HLA-B27 genotyping and magnetic resonance imaging of sacroiliac joints were performed in all patients. One hundred forty-nine patients with chronic inflammatory back pain (IBP) not caused by axSpA served as controls, and additional controls included 50 AS patients and 100 blood donors whose specimens were analyzed. RESULTS: One hundred patients with inflammatory back pain received a diagnosis of nonradiographic axSpA from the investigators and fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criteria. The mean age was 29 years, and the mean symptom duration was 12.5 months. The sensitivity of IgA anti-CD74 and IgG anti-CD74 for identifying the 100 axSpA patients was 47% and 17%, respectively. The specificity of both IgA anti-CD74 and IgG anti-CD74 was 95.3%. The sensitivity of HLA-B27 was 81%. The positive likelihood ratios were 10.0 (IgA anti-CD74), 3.6 (IgG anti-CD74), and 8.1 (HLA-B27). Assuming a 5% pretest probability of axSpA in chronic back pain patients, the posttest probability, after consideration of the respective positive test results, was 33.3% for IgA anti-CD74, 15.3% for IgG anti-CD74, and 28.8% for HLA-B27. A combination of IgA anti-CD74 and HLA-B27 results in a posttest probability of 80.2%. CONCLUSION: IgA anti-CD74 may be a useful tool for identifying axSpA. The diagnostic value of the test in daily practice requires further confirmation.


Assuntos
Antígenos de Diferenciação de Linfócitos B/imunologia , Autoanticorpos/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Espondiloartropatias/imunologia , Adulto , Feminino , Antígeno HLA-B27/genética , Humanos , Imagem por Ressonância Magnética , Masculino , Sensibilidade e Especificidade , Espondilartrite/diagnóstico por imagem , Espondilartrite/genética , Espondilartrite/imunologia , Espondiloartropatias/diagnóstico por imagem , Espondiloartropatias/genética
10.
Infect Dis Ther ; 7(4): 485-494, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30377976

RESUMO

INTRODUCTION: The way syphilis affects the immunologic and virologic parameters of a human immunodeficiency virus (HIV) infection remains controversial. The aim of this study was to investigate the impact of syphilis infection on lymphocyte and lymphocyte subset counts as well as viral load in HIV-infected patients. METHODS: All HIV-infected patients attending the outpatient clinic for infectious diseases of Hannover Medical University Hospital diagnosed with syphilis between 2009 and 2016 were retrospectively evaluated for changes in total lymphocyte, B cell, CD3+ T cell, CD4+ and CD8+ T cell counts as well as in HIV viral load. These parameters were assessed at three different time points, i.e., 3-6 months before, at diagnosis and 3-6 months after treatment of syphilis. RESULTS: Eighty-four HIV-infected patients, all with early syphilis, were identified. The vast majority were men who have sex with men (MSM), and 80% were receiving antiretroviral therapy (ART). Syphilis was associated with a significant reduction in the total lymphocyte count and counts of all studied lymphocyte subsets, including CD4+ T cells, whose percentage among lymphocytes did not change. No significant changes in HIV viral load were observed at any of the studied time points. Further, antibiotic treatment of syphilis restored lymphocyte counts back to pretreatment levels. CONCLUSION: Syphilis induces a relative non-CD4+ T cell-specific lymphopenia in HIV-infected patients. Our data suggest that serologic testing for syphilis should be considered in HIV-infected MSM in case of an otherwise unexplained drop in total lymphocyte count.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30275412

RESUMO

During the current period of immigration to Western Europe, national healthcare systems are confronted with high numbers of asylum seekers with largely unknown health status. To improve care taking strategies, we assessed healthcare utilization in a large, representative cohort of newly arriving migrants consisting of n = 1533 residents of a reception center in Northern Germany in 2015. Most asylum seekers were young, male adults, and the majority came from the Eastern Mediterranean region. Overall, we observed a frequency of 0.03 visits to the onsite primary healthcare ward per asylum seeker and day of camp residence (IQR 0.0⁻0.07, median duration of residence 38.0 days, IQR 30.0⁻54.25). Female asylum seekers showed higher healthcare utilization rates than their male counterparts, and healthcare utilization was particularly low in asylum seekers in their second decade of life. Furthermore, a significant correlation between time after camp entrance and healthcare utilization behavior occurred: During the first week of camp residence, 37.1 visits/100 asylum seekers were observed, opposed to only 9.5 visits/100 asylum seekers during the sixth week of camp residence. This first data on healthcare utilization in a large, representative asylum seeker cohort entering Western Europe during the current crisis shows that primary care is most needed in the first period directly after arrival. Our dataset may help to raise awareness for refugee and migrant healthcare needs and to adapt care taking strategies accordingly.


Assuntos
Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Refugiados/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Assistência à Saúde , Feminino , Alemanha , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde , Migrantes/estatística & dados numéricos , Adulto Jovem
12.
Artigo em Inglês | MEDLINE | ID: mdl-30189649

RESUMO

Background: Immigration into Europe has reached an all-time high. Provision of coordinated healthcare, especially to refugee women that are at increased risk for adverse pregnancy outcomes, is a challenge for receiving health care systems. Methods: We assessed pregnancy rates and associated primary healthcare needs in three refugee cohorts in Northern Germany during the current crisis. Results: Out of n = 2911 refugees, 18.0% were women of reproductive age, and 9.1% of these were pregnant. Pregnancy was associated with a significant, 3.7-fold increase in primary health care utilization. Language barrier and cultural customs impeded healthcare to some refugee pregnant women. The most common complaints were demand for pregnancy checkup without specific symptoms (48.6%), followed by abdominal pain or urinary tract infections (in 11.4% of cases each). In 4.2% of pregnancies, severe complications such as syphilis or suicide attempts occurred. Discussion: We present data on pregnancy rates and pregnancy associated medical need in three current refugee cohorts upon arrival in Germany. Healthcare providers should be particularly aware of the requirements of pregnant migrants and should adapt primary caretaking strategies accordingly.


Assuntos
Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Resultado da Gravidez/etnologia , Gestantes , Refugiados , Adulto , Características Culturais , Feminino , Alemanha/epidemiologia , Humanos , Linguagem , Determinação de Necessidades de Cuidados de Saúde , Gravidez , Fatores Socioeconômicos
15.
AIDS ; 32(3): 299-307, 2018 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-29135573

RESUMO

OBJECTIVE: The formation of large intracellular protein aggregates of the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a caspase-recruitment domain; also know as PYCARD) is a hallmark of inflammasome activation. ASC speck-forming cells release the highly proinflammatory cytokine IL-1ß in addition to ASC specks into the extracellular space during pyroptotic cell death. There ASC specks can propagate inflammation to other nonactivated cells or tissues. HIV-1 retroviral infection triggers inflammasome activation of abortively infected CD4⁺ T cells in secondary lymphatic tissues. However, if pyroptosis occurs in other peripheral blood mononuclear cells (PBMCs) of HIV-1-infected patients is currently unknown. We investigated if ASC speck positive cells are present in the circulation of HIV-1-infected patients. DESIGN AND METHODS: PBMCs or plasma of HIV-1 infected, antiretroviral therapy-naive patients were analyzed for the presence of ASC speck⁺ cells or extracellular ASC and compared with healthy controls. Intracellular staining for ASC was employed to detect ASC speck⁺ cells within PBMCs by flow cytometry, and ELISA to detect free ASC in the plasma. ASC multimerization was confirmed by immunoblot. RESULTS: Peripheral blood CD14⁺⁺CD16⁻ monocytes were ASC speck⁺ in HIV patients, but not in healthy controls. In the subgroup analysis, HIV patients with lower CD4⁺ T-cell counts and higher viral load had significantly more ASC speck⁺ monocytes. ASC speck formation did not correlate with Gag expression, coinfection, lactate dehydrogenase or C-reactive protein. CONCLUSION: Our findings suggest that pyroptotic CD14⁺⁺CD16⁻ classical monocytes of HIV-1-infected patients release ASC specks into the blood stream, a phenomenon that may contribute to HIV-1 induced inflammation and immune activation.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/análise , Infecções por HIV/patologia , Inflamassomos/metabolismo , Monócitos/química , Adulto , Contagem de Linfócito CD4 , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Proteínas Ligadas por GPI/análise , Humanos , Immunoblotting , Receptores de Lipopolissacarídeos/análise , Masculino , Pessoa de Meia-Idade , Receptores de IgG/análise , Coloração e Rotulagem , Carga Viral
16.
Eur J Immunol ; 48(4): 696-704, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29277896

RESUMO

IgG Fc receptors (FcγRs) and the C5a anaphylatoxin receptor (C5aR) were identified as key regulators of type II autoimmune injury in mice. However, and with respect to C5aR, the relative importance of C5a for IgG autoantibody-induced cellular destruction remained unclear. Using an experimental model of autoimmune hemolytic anemia (AIHA), we here report marked differences in the development of AIHA between mice lacking C5aR and C5-deficient (Hc0 ) strain, indicating a limited role of C5 in this type of C5aR-regulated disease. Ex-vivo-analyses of liver homogenates from anemic Hc0 mice demonstrate C5a-independent C5aR activation, upregulation of FcγR expression and amplification of erythrophagocytosis by macrophages. As assessed by pharmacological inhibition studies, targeting of C5aR, but not of C5, is effective in treating experimental AIHA. Collectively, these results define a previously unrecognized disease mechanism of C5aR activation in AIHA that does not necessarily involve C5 and C5a.


Assuntos
Anemia Hemolítica Autoimune/imunologia , Autoimunidade/imunologia , Complemento C5a/deficiência , Macrófagos do Fígado/imunologia , Receptor da Anafilatoxina C5a/metabolismo , Receptores de IgG/imunologia , Animais , Eritrócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fagocitose/imunologia , Receptor da Anafilatoxina C5a/antagonistas & inibidores , Receptor da Anafilatoxina C5a/genética , Receptores de IgG/biossíntese
17.
Inflammation ; 41(1): 42-49, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28852968

RESUMO

Store-operated calcium entry (SOCE) is the most common mode of calcium influx in non-excitable cells, including immune cells. The two STIM isoforms mediate SOCE as well as Fc receptor (FcR)-downstream activation of macrophages and mast cells-which appears to be relevant in vivo, in models of antibody-dependent tissue injury and allergy. Hence, the pathway of SOCE may be a therapeutic target for treatment of immune complex (IC)-mediated autoimmunity and allergic asthma. The pyrazole derivative, BTP2 is an efficient inhibitor of SOCE, which has already been shown to attenuate allergic inflammation. However, its effect on Fc gamma receptor (FcγR) signaling and IC-induced tissue injury had not yet been studied. Here, we show that BTP2 is a potent inhibitor of SOCE in primary macrophages, blocking FcγR-mediated responses. To investigate the effect of inhibition of SOCE in IC-mediated tissue injury, we induced reverse passive Arthus reaction to IgG immune complexes in the skin and lungs of BTP2- or control-treated mice. Treatment with BTP2 resulted in markedly attenuated inflammation in both the skin and the lungs. Our findings indicate the involvement of SOCE in FcγR-mediated responses in vitro and in vivo and suggest that BTP2-mediated inhibition of SOCE may have a therapeutic potential on IC-mediated autoimmunity.


Assuntos
Anilidas/farmacologia , Anti-Inflamatórios/farmacologia , Complexo Antígeno-Anticorpo/imunologia , Reação de Arthus/prevenção & controle , Imunoglobulina G/imunologia , Macrófagos Peritoneais/efeitos dos fármacos , Pneumonia/prevenção & controle , Tiadiazóis/farmacologia , Animais , Complexo Antígeno-Anticorpo/metabolismo , Reação de Arthus/imunologia , Reação de Arthus/metabolismo , Autoimunidade/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Imunoglobulina G/metabolismo , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Camundongos Endogâmicos C57BL , Fagocitose/efeitos dos fármacos , Pneumonia/imunologia , Pneumonia/metabolismo , Receptores de IgG/imunologia , Receptores de IgG/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Fatores de Tempo
18.
Clin Pract ; 8(4): 1095, 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30631410

RESUMO

Generalized lymphadenopathy is a common cause of concern for both patients and clinicians. Possible etiologies include infections, malignancies and autoimmune diseases. Kikuchi Fujimoto disease (KFD) is a hyperergic condition that presents with fever, lymphadenopathy and can include systemic involvement, thus being easily mistaken for the above-mentioned entities. We report the case of a previously healthy 18- year old male who presented with a selflimiting generalized lymphadenopathy, high fevers, skin vasculitis and polyserositis. The lymph-node biopsy revealed a histiocytotic necrotizing lymphadenitis, suggestive of Kikuchi's disease. This case emphasizes the importance of KFD in the differential diagnosis of lymphadenopathy, especially in young adults.

19.
Front Cardiovasc Med ; 5: 170, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30619882

RESUMO

Background: Anti-beta-1-adrenergic receptor antibodies (anti-ß1AR Ab) are associated with ischemic cardiomyopathies (ICM). Evidence continues to emerge supporting an autoimmune component to various cardiac diseases. This study compares anti-ß1AR Ab concentrations in patients with different entities of acute coronary syndromes (ACS) to asymptomatic non-ACS patients with positron-emission computed tomography (PET/CT)-proven atherosclerosis, and healthy controls. Methods: Serum anti-ß1AR Ab IgG concentrations were measured in 212 ACS patients, 100 atherosclerosis patients, and 62 controls using ELISA. All ACS patients underwent coronary angiography. All 374 patients participating completed a structured questionnaire regarding traditional cardiovascular risk factors. ACS patients were followed up for 6 months. Results: Patients with ACS exhibited lower anti-ß1AR Ab levels compared to patients with atherosclerosis or healthy controls (both p < 0.001). No differences in the ab levels were evident between healthy controls and patients with atherosclerosis. In the ACS groups, lower concentrations were found in patients with ST-elevation myocardial infarction (STEMI) (0.67 µg/ml) compared to patients with angina pectoris (AP) and non-ST elevation myocardial infarction (NSTEMI) (both 0.76 µg/ml, p = 0.008). Anti-ß1AR Ab levels ≤ 0.772 µg/ml were predictive for death and reinfarction (AUC 0.77, p = 0.006). No significant correlations between anti-ß1AR Ab levels and atherosclerotic burden or traditional cardiovascular risk factors were identified. Conclusions: Lower anti-ß1AR Ab concentrations appear to characterize ACS phenotypes and could serve as diagnostic and prognostic markers independent from traditional risk factors for atheroscle. The prognostic predictive value of anti-ß1AR Ab in ACS remains to be confirmed in larger studies.

20.
Cells ; 8(1)2018 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-30597851

RESUMO

Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in multiple sclerosis (MS) patients and has recently been approved for the treatment of patients with relapsing MS (RMS) and primary progressive MS (PPMS). CD20 is mainly expressed by B cells, but a subset of T cells (CD3⁺CD20⁺ T cells) also expresses CD20, and these CD20⁺ T cells are known to be a highly activated cell population. The blood of MS patients was analyzed with multicolor flow cytometry before and two weeks after treatment with ocrelizumab regarding the phenotype of peripheral blood mononuclear cells. CD20-expressing CD3⁺ T cells were found in blood samples of all MS patients, accounted for 2.4% of CD45⁺ lymphocytes, and constituted a significant proportion (18.4%) of all CD20⁺ cells. CD3⁺CD20⁺ T cells and CD19⁺CD20⁺ B cells were effectively depleted two weeks after a single administration of 300 mg ocrelizumab. Our results demonstrate that treatment with ocrelizumab does not exclusively target B cells, but also CD20⁺ T cells, which account for a substantial amount of CD20-expressing cells. Thus, we speculate that the efficacy of ocrelizumab might also be mediated by the depletion of CD20-expressing T cells.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Antígenos CD20/imunologia , Linfócitos B/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Subpopulações de Linfócitos T/efeitos dos fármacos , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Citotoxicidade Imunológica , Progressão da Doença , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva
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