RESUMO
BACKGROUND: Splenectomy is a therapy for patients with treatment-refractory autoimmune cytopenias. Antiphospholipid antibodies (aPL) can be identified in 25%-85% of these patients. In this study, we sought to identify whether the presence of aPL was associated with worse outcomes in autoimmune cytopenia's patients who had undergone splenectomy. METHODS: We conducted a retrospective cohort study of patients who underwent splenectomy from 2000 to 2018. We describe clinical characteristics and outcomes in patients with autoimmune cytopenia's diagnosis with positive determinations of aPL. Additionally, we performed a case-control sub-analysis 1:1 of the cases with autoimmune cytopenia's matched control patients with negative aPL determination. RESULTS: A splenectomy was performed in 707 patients, of which we included 34 for the analysis. The median age at the time of splenectomy was 37 years (range 19-61), 53% corresponded to immune thrombocytopenia (ITP) and 47% to autoimmune hemolytic anemia (AIHA). Compared with controls (n = 34), patients had more treatment lines in addition to steroids (p = .02). There were no differences in complete response rate, 65% in cases and 80% in controls (p = .17). However, there was numerically a higher incidence of early infections (21% of cases vs. 3% controls, p = .05). During the entire follow-up, 15% of aPL patients compared with 9% of control patients had a thrombotic event (p = .70). DISCUSSION: Splenectomy for treatment-refractory autoimmune cytopenia's patients with persistent aPL is an effective treatment despite some safety concerns related to early infections. These results suggest that the presence of aPL should not impact the decision to undergo splenectomy.
Assuntos
Anticorpos Antifosfolipídeos , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Although chiefly a B-lymphocyte disorder, several research groups have identified common variable immunodeficiency (CVID) subjects with numeric and/or functional TH cell alterations. The causes, interrelationships, and consequences of CVID-associated CD4+ T-cell derangements to hypogammaglobulinemia, autoantibody production, or both remain unclear. OBJECTIVE: We sought to determine how circulating CD4+ T cells are altered in CVID subjects with autoimmune cytopenias (AICs; CVID+AIC) and the causes of these derangements. METHODS: Using hypothesis-generating, high-dimensional single-cell analyses, we created comprehensive phenotypic maps of circulating CD4+ T cells. Differences between subject groups were confirmed in a large and genetically diverse cohort of CVID subjects (n = 69) by using flow cytometry, transcriptional profiling, multiplex cytokine/chemokine detection, and a suite of in vitro functional assays measuring naive T-cell differentiation, B-cell/T-cell cocultures, and regulatory T-cell suppression. RESULTS: Although CD4+ TH cell profiles from healthy donors and CVID subjects without AICs were virtually indistinguishable, T cells from CVID+AIC subjects exhibited follicular features as early as thymic egress. Follicular skewing correlated with IgA deficiency-associated endotoxemia and endotoxin-induced expression of activin A and inducible T-cell costimulator ligand. The resulting enlarged circulating follicular helper T-cell population from CVID+AIC subjects provided efficient help to receptive healthy donor B cells but not unresponsive CVID B cells. Despite this, circulating follicular helper T cells from CVID+AIC subjects exhibited aberrant transcriptional profiles and altered chemokine/cytokine receptor expression patterns that interfered with regulatory T-cell suppression assays and were associated with autoantibody production. CONCLUSIONS: Endotoxemia is associated with early commitment to the follicular T-cell lineage in IgA-deficient CVID subjects, particularly those with AICs.
Assuntos
Linfócitos B/imunologia , Diferenciação Celular/imunologia , Imunodeficiência de Variável Comum/imunologia , Endotoxemia/imunologia , Deficiência de IgA/imunologia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Linfócitos B/patologia , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/patologia , Endotoxemia/patologia , Feminino , Humanos , Deficiência de IgA/patologia , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/patologiaRESUMO
The term autoimmune cytopenias is referred to a heterogeneous group of diseases characterized by a reduced peripheral blood cell counts in one or more cellular series, because an immunological disorder. The first line therapy is steroids, followed by splenectomy or immunesupressant therapy in non-responders. Rituximab is an anti CD20 monoclonal antibody used as a third line in refractory patients or as an alternative to splenectomy. We present a retrospective study of nine patients with autoimmune cytopenias treated in a public hospital setting with rituximab. Five patients with the diagnosis of inmune thrombocytopenic purpura received it, all of them achieved hematological response (4 complete and one partial). The median time to the best response was 6 weeks, staying in this category after 6 months of follow up. Four patients with autoimmune hemolytic anemia received rituximab, three of them achieving partial response and one was lost from follow up. No severe adverse effects related to rituximab were registered.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Doenças Autoimunes/tratamento farmacológico , Trombocitopenia/tratamento farmacológico , Anticorpos Monoclonais Murinos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Anemia Hemolítica Autoimune/tratamento farmacológico , Neutropenia/tratamento farmacológico , Estudos Retrospectivos , Púrpura Trombocitopênica Idiopática/imunologia , Rituximab/administração & dosagemRESUMO
Las citopenias hematológicas son un hallazgo frecuente y potencialmente grave en las Enfermedades Autoinmunes Sistémicas. Sus causas pueden ser muy variadas, de ahí la importancia de un abordaje diagnóstico sistematizado que asegure además el tratamiento correcto. En este artículo se revisan las generalidades de las citopenias hematológicas en cuanto a frecuencia, causas, así como su enfoque diagnóstico y terapéutico.
The hematologic cytopenias are a frequent and potentially dangerous finding in the Systemic Autoimmune Diseases. It may have different etiologies, and for that reason it is important a systematic approach to ensure the correct diagnosis and treatment. In this article, the frequency, etiology, diagnostic approach and treatment of the hematologic cytopenias are reviewed.
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B+NK+SCID (severe combined immunodeficiency) due to IL7Rα deficiency represents approximately 10% of American SCID cases. To better understand the spectrum of autoimmune disorders associated with IL7Rα deficiency, we describe two unrelated IL7Rα-deficient female SCID infants whose clinical picture was dominated by autoimmune manifestations: one with intrauterine Omenn syndrome (OS) and another with persistent thrombocytopenic purpura since 4months of age. The OS baby harbored a homozygous p.C118Y mutation in IL7R. She presented dense eosinophilic infiltrates in several organs, including pancarditis, which may have contributed to her death (on the 2nd day of life). B cells were observed in lymph nodes, spleen, bone marrow and thymus. The second patient harbored compound heterozygous p.C118Y and p.I121NfsX8 mutations. She underwent a successful unrelated cord blood transplant. In conclusion, early OS can be observed in patients with IL7R mutations, and autoimmune cytopenias could also complicate the clinical course of SCID babies with this type of defect.