Lower expression of plasma-derived exosome miR-21 levels in HIV-1 elite controllers with decreasing CD4 T cell count

Exosome-derived miR-21 was independently associated with CD4 T cell decline in HIV-1-infected elite controllers (OR 0.369, 95% CI 0.137–0.994, p = 0.049). Also, a negative correlation between miR-21 expression and MCP-1 level was found (r = −0.649, p = 0.020), while no correlation between soluble biomarkers or cellular immune activation was found.     

Suppressed immune profile in children with combined type 1 diabetes and celiac disease

Children diagnosed with a combination of type 1 diabetes (T1D) and celiac disease (CD) show a dysregulated T helper type 1 (Th1)/Th17 response. Besides the cellular involvement, several soluble immune markers are involved in the autoimmune process of both T1D and CD. Only few studies have examined the peripheral pattern of different cytokines, chemokines and acute-phase proteins (APP) in children with combined T1D and CD. To our knowledge, no studies have evaluated the serum levels of adipocytokines and matrix metalloproteinases (MMPs) in this context. The purpose of the present study was to acquire more knowledge and to gain deeper understanding regarding the peripheral immunoregulatory milieu in children with both T1D and CD. The study included children diagnosed with both T1D and CD (n = 18), children with T1D (n = 27) or CD (n = 16) and reference children (n = 42). Sera were collected and analysis of 28 immune markers (cytokines, chemokines, APPs, adipocytokines and MMPs) was performed using the Luminex technique. The major findings showed that children with a double diagnosis had lower serum levels of interleukin (IL)-22, monocyte chemoattractant protein (MIP)-1α, monocyte chemoattractant protein (MCP)-1, procalcitonin, fibrinogen, visfatin and matrix metalloproteinase (MMP)-2. These results indicate a suppressed immune profile in children with combined T1D and CD, including Th17 cytokines, chemokines, APPs, adipocytokines and MMPs. We conclude that, besides cytokines and chemokines, other immune markers, e.g. APPs, adipocytokines and MMPs, are of importance for further investigations to elucidate the heterogeneous immune processes present in patients diagnosed with T1D in combination with CD.     

Assessment of CD8 T cell immune activation markers to monitor response to antiretroviral therapy among HIV-1 infected patients in Côte d'Ivoire

Because of the paucity of plasma HIV RNA viral load (VL) tests in resource‐poor settings, the CD4⁺ T cell count is often used as the sole laboratory marker to evaluate the effectiveness of antiretroviral therapy (ART) in HIV‐infected patients. In untreated patients, the level of activated T cells is positively correlated with VL and represents a prognostic marker of HIV infection. However, little is known about its value to predict early drug failure, taking into account the relatively high non‐specific immune activation background observed in many resource‐limited tropical countries. We assessed the use of immune activation markers (expression of CD38 and/or human leucocyte antigen‐DR on CD8⁺ lymphocytes) to predict virological response to ART in a cohort of HIV‐1 infected patients in Abidjan, Côte d’Ivoire. Correlations between VL, absolute CD4⁺ T cell counts and immune activation levels were examined in 111 HIV patient samples at baseline and after 6 and 12 months of therapy. The percentage of CD38⁺ CD8⁺ T cells appeared to be the best correlate of VL. In contrast, changes in CD4⁺ T cell counts provided a poor correlate of virological response to ART. Unfortunately, CD38⁺ CD8⁺ percentages lacked specificity for the determination of early virological drug failure and did not appear to be reliable surrogates of RNA viral load. CD38⁺ CD8⁺ T cell percentages may, rather, provide a sensitive estimate of the overall immune recovery, and be a useful extra laboratory parameter to CD4 counts that would contribute to improve the clinical management of HIV‐infected people when VL testing facilities are lacking.     

急性免疫性血小板减少症患儿血清IL-33检测及其意义

为研究IL-33在儿童急性免疫性血小板减少症(ITP)发病机制中的作用及意义,我们采用ELISA法检测了37名ITP患儿和37名对照者血清IL-33水平,分析IL-33与患儿就诊时血小板计数及后期疗效的关系。我们发现,ITP患儿血清IL-33较对照者明显增高(P<0.01),且与血小板计数呈负相关(R2=0.10,P=0.05)。血清IL-33水平与治疗效果密切相关,采用IL-33预测ITP患儿疗效,预测敏感性为0.88,特异性为0.81。这些结果提示:IL-33参与了ITP的发病机制,血清IL-33水平可以作为预测患儿疗效的免疫学指标。     

Expression of CD markers' in immune thrombocytopenic purpura: prognostic approaches

Immune Thrombocytopenic Purpura (ITP) is a common autoimmune bleeding disorder characterized by a reduction in peripheral blood platelet counts. In this disease, autoantibodies (Auto‐Abs) are produced against platelet GPIIb/GPIIIa by B cells, which require interaction with T cells. In this review, the importance of B and T lymphocytes in ITP prognosis has been studied. Relevant literature was identified by a PubMed search (1990–2016) of English‐language papers using the terms B and T lymphocyte, platelet, CD markers and immune thrombocytopenic purpura. T and B lymphocytes are the main immune cells in the body. Defective function causes disrupted balance of different subgroups of lymphocytes, and abnormal expression of surface markers of these cells results in self‐tolerance dysfunction, as well as induction of Auto‐Abs against platelet glycoproteins (PG). Given the role of B and T cells in production of autoantibodies against PG, it can be stated that the detection of changes in CD markers' expression in these cells can be a good approach for assessing prognosis in ITP patients.     

Intravenous immunoglobulin does not increase FcγRIIB expression levels on monocytes in children with immune thrombocytopenia

Intravenous immunoglobulin (IVIG) produces a rapid and prolonged increase in the platelet counts of children with immune thrombocytopenia (ITP). The mechanism of IVIG efficacy in a murine model of ITP has been reported to operate through an IVIG-mediated increase in the expression of the inhibitory Fc receptor FcγRIIB(CD32B) on splenic macrophages. This investigation examined whether IVIG administration results in a similar increase in FcγRIIB expression on peripheral blood CD14(+) monocytes in 20 children with ITP. FcγRIIB expression on peripheral blood monocytes was measured by flow cytometry in ITP patients, before and after IVIG therapy, as well as in control subjects. Peripheral blood monocytes were labelled with fluorescent-specific antibodies. There were no significant differences in the percentages or numbers of CD14(+) CD32B(+) monocytes, or in the percentage of CD14(+) CD32B(+) monocytes present in children with ITP before and after IVIG therapy. We suggest that IVIG does not increase FcγRIIB expression in peripheral blood monocytes in children with ITP.     

Simultaneous Occurrence of Immune-Mediated Thrombocytopenia and Myocarditis After mRNA-1273 COVID-19 Vaccination: A Case Report

With the global spread of severe acute respiratory syndrome coronavirus 2, several vaccines were developed; messenger RNA (mRNA) vaccines have recently been widely used worldwide. However, the incidence of myocarditis following mRNA vaccination is increasing; although the cause of myocarditis has not yet been clearly identified, it is presumed to be caused by a problem in the innate immune system. Immune-mediated thrombocytopenia (ITP) after vaccination is rare but has been reported and is also assumed to occur by the same mechanism. We report the first case of simultaneous myocarditis and ITP after mRNA vaccination. A 38-year-old woman presented with chest pain, mild dyspnea, and sweating after vaccination with mRNA-1273 vaccine (Moderna) 4 days prior to admission. Upon admission to the emergency department, cardiac enzymes were elevated; blood test performed 5 months ago showed normal platelet count, but severe thrombocytopenia was observed upon admission. After administration of intravenous immunoglobulin, the platelet count improved; subsequently, myocarditis was observed on endomyocardial biopsy. Thus, myocarditis and ITP were judged to have occurred simultaneously due to the expression of the innate immune system markers after mRNA vaccination. The patient was discharged on day 6 of admission.     

High-Dose Dexamethasone Inhibits BAFF Expression in Patients with Immune Thrombocytopenia

Introduction  B-cell activating factor belonging to the TNF family (BAFF) is elevated in several autoimmune diseases including immune thrombocytopenia (ITP). High-dose dexamethasone (HD-DXM) has shown its clinical efficacy in ITP patients. Materials and Methods  The plasma BAFF concentration and BAFF mRNA were measured in ITP patients before and after oral administration of 40 mg/day DXM for four consecutive days by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR. Moreover, we evaluated the effects of DXM on BAFF expression and proliferation of lymphocytes by ELISA, real-time quantitative PCR and cell proliferation respectively in in vitro experiment. Results  Both plasma BAFF concentration and BAFF mRNA were significantly increased in active ITP patients at pretherapy when compared with controls (P < 0.001). After 4-day treatment with HD-DXM, the BAFF and BAFF mRNA were decreased, and lower than that for controls. In in vitro assays, we found DXM-inhibited BAFF, IFN-γ expression, and the proliferation of lymphocytes in a dose-dependent manner. Conclusion  These results suggest that BAFF expression is increased in ITP patients with active disease, and DXM is an effective inhibitor of BAFF production. As immunosuppressant, DXM may play its role in ITP treatment partly through regulating BAFF expression. Xiao-juan Zhu, Yan Shi, and Jian-zhi Sun contributed equally to this work.     

Increased CD200 expression in post-transplant lymphoproliferative disorders correlates with an increased frequency of FoxP3(+) regulatory T cells

CD200 is a membrane protein with immunosuppressive function and is expressed in many hematopoietic neoplasms, including acute myeloid leukemia (AML), plasma cell myeloma (PCM), and B-cell lymphoproliferative disorders, but is mostly negative in diffuse large cell lymphoma (DLBCL). CD200 has been shown to be a poor prognostic marker in AML and PCM; in AML, its immunomodulatory effect was linked to its ability to induce FoxP3(+) regulatory T cells (Tregs). Post-transplant lymphoproliferative disorders (PTLDs) arise in the setting of immune dysregulation, and tumor-infiltrating T cells, including Tregs, have been shown to correlate with outcome in these disorders. Because there is no literature data and CD200 is a potentially useful diagnostic and prognostic marker, we studied the expression of CD200 in a series of 38 PTLDs by immunohistochemistry (ICH), and found that 23.7% PTLDs were CD200(+) and showed strong membrane and cytoplasmic positivity in the neoplastic cells. All CD200(+) monomorphic PTLDs were DLBCLs and the median FoxP3(+) Treg count/hpf was higher in CD200(+) than in CD200(−) PTLDs: 22.6 vs. 0.30 (p < 0.001). These results indicated that almost a quarter of PTLDs in our series are CD200(+) by IHC, and CD200 expression correlates with the frequency of immunosuppressive Tregs. This is novel data and supports a pathophysiologic link between CD200 activity and Tregs. In our series, the 5-year overall survival was shorter in CD200(+) PTLDs, compared to CD200(−) patients, although this difference did not reach statistical significance. In addition, we find a higher proportion of CD200(+) monomorphic PTLD-DLBCLs (31.0%), as compared to de novo DLBCLs (7–8%, as found here and in other studies). This may indicate differential expression of CD200 in B-cell lymphomas arising in the setting of immune dysregulation, and raises the possibility of anti-CD200 immunotherapy for these cases.     

Predictive value of immunologic and virologic markers after long or short duration of HIV-1 infection

Laboratory markers that predict HIV-1 disease progression include plasma viral burden, CD4+ T-cell count, and CD38 expression on CD8 T cells. To better understand whether the predictive value of these markers is dependent on how long an individual has been infected, we analyzed data from the Multicenter AIDS Cohort Study early (median = 2.8 years) and late (median = 8.7 years) in the course of infection. Overall, we found that HIV RNA and CD38 levels were similarly predictive of AIDS early on compared with a relatively weaker CD4 cell count signal. Later in the course of infection, CD38 level remained the strongest predictive marker and CD4 cell count registered a marked increase in prognostic power. Among untreated individuals, there was little difference in prognosis (median time to AIDS) associated with given marker values regardless of infection duration. The prognosis given a specific viral load level tended to deteriorate late in the course of infection among those undergoing treatment with monotherapy or combination therapy, however. These data provide a unique historical look at the predictive value and prognostic significance of HIV-1 disease markers at different stages of infection in a large cohort, with direct relevance to current patients who are untreated or for whom treatment is ineffective.     

Hyperglycemia and dyslipidemia: Reduced HLA-DR expression in monocyte subpopulations from diabetes patients

Immune dysfunction contributes to the higher risk of communicable and non-communicable diseases among diabetics. HLA-DR expression is a robust marker of immune competence in mononuclear cells, including antigen presentation to CD4 lymphocytes. Given the high prevalence of obesity among diabetics, we evaluated the independent association between hyperglycemia and dyslipidemias with respect to HLA-DR expression in blood monocytes from type 2 diabetes patients. The monocytes from individuals with (n = 16) or without diabetes (n = 25) were phenotyped by flow cytometry to assess the differential expression of HLA-DR on their three subpopulations (classical, intermediate and non-classical monocytes). Diabetes was independently associated with lower HLA-DR expression across all monocyte subpopulations (p < 0.05). Blood triglycerides were associated with further HLA-DR depression (interaction p < 0.002). Cholesterols counterbalanced the reductive effect, with CD36, a receptor for oxidized cholesterol, correlating with HLA-DR (rho = 0.373; p = 0.016). Future studies are warranted to elucidate the complex interactions between hyperglycemia and dyslipidemias on antigen presentation in diabetic monocytes.     

Prognostic significance of E-cadherin and Cox 2 expression in Tunisian patients with colorectal mucinous adenocarcinoma

IntroductionMucinous colorectal carcinoma (MC) is a rare subtype of colorectal adenocarcinoma known to be associated with bad prognosis. Lately, research has turned to identify new prognostic markers allowing the use of targeted therapy. The aim of our study is to evaluate the prognostic impact of E-cadherin and Cox-2expression in MC.Materials and methodA total of 40 formalin-fixed, paraffin-embedded MC specimens were collected within a period of 13 years and were studied for the expression of the two proteins. We used SPSS 22 software to study associations with clinicopathological parameters and overall survival (OS).ResultsA reduced or absent E-cadherin expression was noted in 52.5% of cases. It was associated with distant metastases (p = 0.049) and venous invasion (p = 0.049). Cox-2 was overexpressed in 17.5% of cases. It was associated with negative lymph node status (p = 0.020) and with early stage tumor (p = 0.020). A significant association between the two proteins was also noted (p = 0.04). No significant association with OS was found; However, there was an improvement in the survival of patients overexpressing Cox-2 (p = 0.16).ConclusionOur findings link the loss of E-cadherin expression with spread and aggressiveness in MC and Cox-2 overexpression with better prognosis and survival. Because MC has a distinct genetic pathway we encourage the analysis of MSI and Cox-2 expression in all MC. Cox-2 inhibitors may not be effective chemopreventative agents in the setting of defective DNA mismatch repair. More molecular studies are needed to better understand the role of these markers and their prognostic significance in MC.     

Decreased TLR4 expression on monocytes may cause regulatory T cells abnormality in patients with primary immune thrombocytopenia

Primary immune thrombocytopenia (ITP) is an autoimmune disease with many immune dysfunctions including T helper type 1 cell (Th1) polarization and regulatory T cells (Tregs) deficiency. This study aimed to determine the effects of TLR4 on Treg differentiation and the cytokine production of peripheral blood mononuclear cells (PBMCs) from patients with ITP. We found that expression of TLR4 on monocytes was significantly decreased in patients with active ITP than that in healthy controls and it had positive correlation with platelet count. However, there was no expression of TLR4 on CD4⁺ T cells. The result of further experiments in vitro showed that lipopolysaccharide (LPS) stimulation could enhance TLR4 expression on monocytes. Additionally, activation of TLR4 with LPS could promote differentiation of Treg cells and anti-TLR4 attenuated this effect. There was no significant difference about Th17 cells among three subgroups. However, the Th17/Treg cell ratio was decreased after stimulation with LPS and increased with anti-TLR4. Moreover, activation of TLR4 with LPS could significantly promote the secretion of interleukin-10 (IL-10) and transforming growth factor-β1 (TGFB1), while anti-TLR4 significantly suppressed the secretion of them. Nevertheless, the secretion of IL-17A did not reach the statistical difference among three subgroups. In summary, decreased TLR4 appears to cause Tregs abnormality in ITP by modulating Tregs differentiation and immunoregulatory cytokines.     

CCR6 defines a subset of activated memory T cells of Th17 potential in immune thrombocytopenia

Current researches have determined the significance of C-C chemokine receptor (CCR)6 expression as either a marker of T helper cells (Th) or an effector and regulator of T cell function. However, the roles of CCR6 in the pathogenesis of immune thrombocytopenia (ITP) are unclear. In this study, we aimed to investigate the phenotype and functional characteristics of circulating CCR6⁺ T cells in blood from chronic ITP patients and healthy controls. We found that the frequency of CCR6⁺CD4⁺ cells was higher in ITP patients than in healthy controls. Anti-CD3/anti-CD28 stimulation induced rapid expansion of CCR6⁺CD4⁺ cells in ITP patients. CCR6⁺CD4⁺ cells had a phenotype of activated cells and predominantly expressed CD45RO. Forkhead box protein P3 (FoxP3) and CD25-positive cells were exclusively detected within the CCR6⁺CD4⁺ cells. In ITP patients, CCR6⁺ regulatory T cells (T_reg) were decreased and positively correlated with platelet counts and transforming growth factor (TGF)-β plasma levels. In contrast to CCR6^– counterparts, CCR6⁺CD4⁺ cells produced higher levels of interleukin (IL)-17A. The frequency of CCR6⁺ Th17 was higher in ITP patients and positively correlated with IL-17A levels in supernatant. Most importantly, CCR6⁺CD4⁺ cell subpopulations, but not CCR6⁻CD4⁺, were closely correlated to treatment response of ITP patients. These findings suggest that circulating CCR6⁺CD4⁺ cells in ITP patients have characteristics of activated memory Th17 phenotype and could be used to monitor disease activity and treatment response.     

The experience of Flebogammadif® in primary immune thrombocytopenia

Primary immune thrombocytopenia (ITP) is a common autoimmune disease characterized by autoantibody-induced platelet destruction, suboptimal megakaryocytic production of platelets and consequent bleeding. Numerous controlled trials have proved that the administration of high-dose intravenous immunoglobulins (IVIG) results in rapid increases in the platelet numbers. Therefore, they are indicated in emergency settings or in patients needing surgical procedures. Here, the efficacy and safety of Flebogammadif?, a new high-purity IVIG, was assessed by an open, multi-centre, non-controlled, prospective study in 20 adult patients diagnosed with ITP for at least 6 months before recruitment and with a platelet count ≤ 20,000/μl before treatment. Patients received 0·4 g/kg/body weight of Flebogammadif? for 5 consecutive days and were followed-up for 3 months. There were three efficacy end-points: proportion of patients who reached a platelet count ≥ 50 000/μl; time for the platelet count to reach that level; and duration of response. Safety parameters [adverse events (AE), laboratory determinations and vital signs] and viral markers were monitored regularly. A total of 14 patients achieved a platelet count of ≥ 50,000/μl. The median time to platelet response was ≤ 2·5 days and the median number of days in which the platelet count remained ≥ 50,000/μl was ≥ 7·0 days. A regression of haemorrhages was reported for 17 patients on day 14. Eight patients presented 20 AEs (mainly mild) related potentially to the study drug. Neither abnormalities in laboratory values nor in viral markers were registered during the follow-up period. In conclusion, Flebogammadif? was well tolerated and succeeded in providing a haemostatic platelet count in ITP patients.     

The role of ALDH1A1 in contributing to breast tumour aggressiveness: A study conducted in an African population

Aldehyde dehydrogenase 1 member A1 (ALDH1A1) is one of the most well studied breast cancer stem cells. Its expression has been associated with poor clinicopathological features and clinical outcomes in several studies. This paper studies the expression of ALDH1A1 and its combination with CD44⁺/CD24^−/low breast cancer stem cell and their association with clinicopathological parameters and molecular subtypes.MethodTissue Microarray was constructed from 222 Formalin Fixed Paraffin Embedded (FFPE) breast cancer tissues. The expression of ALDH1A1, CD44 and CD24 were assessed by Immunohistochemistry (IHC). The association of ALDH1A1 and its association with clinicopathological parameters, molecular subtypes, CD44 and CD24 were studied in an African population. The association between CD44⁺/CD24^−/low/ALDH1⁺ and the clinicopathological phenotypes were also studied.ResultsA high ALDH1A1 expression of 90% was recorded in this study. No association was found between ALDH1A1 and clinicopathological parameters. ALDH1A1 was positively associated with CD24 (r = 0.228, OR-4.599 95% CI- 1.751–12.076, p = 0.001) and CD44 (r = 0.228, OR-5.538 95%CI- 1.841–16.662, p = 0.001) but not associated with CD44⁺/CD24^−/low (r = 0.134, OR- 2.720 95%CI- 0.959–7.710, p = 0.052). CD44⁺/CD24⁻/ALDH1⁺ however had significant associations with Age (p- 0.020, r = 0.161, OR- 2.771, 95%CI 1.147–6.697), Gender (p = 0.004, OR- 15.333 95%CI 1.339–175.54), Tumour grade (p = 0.005, r = 0.197, OR-3.913 95%CI 1.421–10.776) and clinical prognostic staging (p = 0.014, r = 0.182, OR-3.028 95%CI- 1.217–7.536). There was no association between CD44⁺/CD24⁻/ALDH1⁺ and the molecular subtypes.ConclusionThe high expression of ALDH1A1 in breast cancer makes it an important target for targeted therapy. This study further confirms the increased tumourigenicity of CD44⁺/CD24⁻/ALDH1⁺ combination phenotype and its association with increased tumour grade and clinical prognostic stage. Survival studies of ALDH1A1 and other breast cancer stem cells in African populations are strongly recommended to help further understand their effect on tumour aggressiveness.     

Aberrant deleted in liver cancer‐1 expression is associated with tumor metastasis and poor prognosis in urothelial carcinoma

This study explored the potential role of deleted in liver cancer‐1 (DLC‐1) as a prognostic indicator of cancer metastasis and survival in urothelial carcinoma (UC). Tissue microarrays were constructed from paraffin‐embedded specimens from 88 UC patients, and immunohistochemical staining was performed to investigate the association of DLC‐1 with clinicopathologic characteristics and clinical outcome. The DLC‐1 expression showed a significant positive correlation with tumor location (p = 0.041) and a significant negative correlation with advanced histological grade (p = 0.013). In tumors with low DLC‐1 expression, Bcl‐2 positivity was observed in 24.4% of cases. The DLC‐1 expression had significant negative associations with Bcl‐2 expression (p = 0.032) and with highly metastatic UC (p = 0.032). Kaplan–Meier analysis showed that DLC‐1 protein expression was negatively associated with both overall survival (OS) (p = 0.035) and with distant metastasis‐free survival (DMFS) (p = 0.041), but not with disease‐free survival. Multivariate analyses indicated that tumor size was the significant independent predictors of OS (p = 0.048); however, only DLC‐1 expression was a significant independent predictor of DMFS (p = 0.019). In conclusion, reduced DLC‐1 protein expression may be an important factor in tumor progression and a useful prognostic molecular marker in UC.     

Pierwotna małopłytkowość immunologiczna u dzieci w świetle współczesnych definicji

BackgroundPrimary immune thrombocytopenia (ITP) is one of the most common hematologic disorders in pediatric population. In 2009 the new unified terminology regarding: definition, clinical classification of the disease and response to treatment was proposed. The main study objective was the comparative analysis of clinical aspects of primary ITP in children regarding the contemporary definitions and historical criteria.MethodsData were collected through medical chart review of subjects identified from hospitalization records (Pediatrics, Hematology and Oncology Department) from the period of 2002–2011.ResultsData of 209 subjects were analyzed. According to recent definitions 206/209 patients (98.6%) could be defined. Using the historical criteria 86.12% were classified as acute and 13.88% as chronic ITP. Newly diagnosed primary immune thrombocytopenia was confirmed in 166/206 cases, persistent ITP in 20/206, and chronic ITP in 20/206 of subjects. Depending on applied criteria we noticed significant differences in acute ITP patient number. Regardless of adjusted definitions, the response rates were higher among treated patients (p < 0.0001). Historical criteria allowed to recognize lower response rate in patients treated with intravenous immunoglobulins (p = 0.009) or steroids (p = 0.033).ConclusionsContemporary definitions allow for more adequate categorization on most of the patients with primary immune thrombocytopenia considering the specific clinical aspects and different natural history of primary ITP in children.     

Assessment of changes in immune status linked to COVID-19 convalescent and its clinical severity in patients and uninfected exposed relatives

IntroductionThe immune response during and after SARS-CoV-2 infection can be complex and heterogeneous, and it can be affected by the severity of the disease. It can also contribute to an unfavorable evolution and bring about short and long term effects. The aim of this study was to characterize the lymphocyte composition according to the severity of COVID-19, as well as its degree of relationship to the specific humoral response to SARS-CoV-2 in convalescents up to 106 days after the infection and in their exposed relatives.MethodsAn applied research was carried out with a cross-section analytical design, from March 11 to June 11, 2020 in Cuba. The sample consisted of 251 convalescents from COVID-19 over 18 years of age and 88 exposed controls who did not become ill. The B and T cell subpopulations, including memory T cells, as well as the relationship with the humoral immune response against SARS-CoV-2, were identified by flow cytometry and enzyme immunoassay.ResultsConvalescent patients, who evolved with severe forms, showed a decrease in frequency and a greater proportion of individuals with values ??lower than the minimum normal range of B cells, CD3 + CD4 + cells and the CD4 + / CD8 + ratio, as well as a higher frequency and a greater proportion of individuals with values ??above the normal maximum range of CD3 + CD8 + and NK cells. Convalescent patients with severe forms of COVID-19 that exhibited IgG / RBD titers ≥ 1/200 had a lower frequency of TEMRA CD8 + cells (p = 0.0128) and TEMRA CD4 + (p = 0.0068). IgG / RBD titers were positively correlated with the relative frequency of CD4 + CM T memory cells (r = 0.4352, p = 0.0018).ConclusionsThe identified alterations of B and T lymphocytes suggest that convalescent patients with the severe disease could be vulnerable to infectious, autoimmune or autotinflammatory processes; therefore, these individuals need medical follow-up after recovering from the acute disease. Furthermore, the role of T cells CD4 + CM in the production of antibodies against SARS-CoV-2 is confirmed, and it is noted that the defect of memory T cells CD8 + TEMRA could contribute to the development of severe forms of COVID-19.     

Clinical features of acute human immunodeficiency virus infection in Taiwan: A multicenter study

Background/purposeAcute HIV infection is characterized by a high concentration of HIV RNA in the plasma and rapid depletion of the CD4 cell count. This multicenter, retrospective observational study aimed to characterize the manifestations of acuteHIV infection in Taiwan.MethodsBetween 1 January 2012 and 31 December 2016, all patients aged 20 years or greater who presented with acute HIV infection were included. Demographic and clinical characteristics of the patients at diagnosis were collected. Baseline laboratory assessment included hemogram, CD4 count, plasma HIV RNA load (PVL), serologic markers of syphilis and hepatitis A, B, and C viruses, and serum biochemistry.ResultsThe proportion of acute HIV infection was 6.9% among the patients with newly diagnosed HIV infection during the study period. The most common presenting symptoms of acute HIV infection were fever, fatigue, and myalgia. The median PVL at diagnosis was 5.9 log₁₀ copies/ml, and median CD4 count was 307 cells/mm³. A total of 68 patients (27%) had baseline CD4 count less than 200 cells/mm³. Multiple logistic regression analysis, showed that the baseline CD4 count (OR, 4.02; p = 0.013) and aspartate aminotransaminase levels (OR, 3.49; p = 0.002) were associated with high PVL (>5 log₁₀ copies/ml); and high baseline PVL (OR, 2.64; p = 0.002) was associated with symptomatic acute HIV infection.ConclusionsManifestations of acute HIV infection are nonspecific and of wide spectrum ranging from fever to severe illness. A higher proportion of patients with initial CD4 counts of 200 cells/mm³ or less during acute HIV infection warrants early, timely diagnosis and treatment to prevent rapid disease progression.