This is a single center Phase I clinical trial of FT538 administered intravenously (IV) once every 14 days for 4 consecutive doses for the reduction of the HIV reservoir in lymphoid tissue of HIV-infected individuals receiving standard of care (SOC) antiretroviral therapy (ART). As this is an early 1st in human study and the 1st for HIV-infected individual, the safety of FT538 is confirmed prior to the addition of oral vorinostat to explore the concept of "Kick and Kill".

开始日期2024-07-15

申办/合作机构

University of Minnesota Masonic Cancer Center

NCT06044792

/ Not yet recruitingN/AIIT

The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in Patients Treated With Antiretroviral Drugs - an Observational Cohort Study.

Since the reasons for differential immune reconstitution in HIV-infected patients are still not fully understood, we considered it reasonable to investigate whether the presence of primary HIV drug resistance mutations could be one of the factors of inadequate immune reconstitution.
Evaluation of unfavorable factors of immune reconstitution can help identify patients at risk of persistently low CD4 cell counts and CD4:CD8 ratios and requiring careful monitoring for progression to AIDS.

开始日期2023-09-30

申办/合作机构

Warszawski Uniwersytet Medyczny

NCT02659800

/ Terminated临床1期IIT

A Phase I and Pilot Study of the Effect of rhIL-7-hyFc (NT-I7) on CD4 Counts in Patients With High Grade Gliomas and Severe Treatment-related CD4 Lymphopenia After Concurrent Radiation and Temozolomide

The purpose of this study is to determine the maximum tolerated dose (MTD) and select optimal biological doses (OBD) of the study drug NT-I7 in High Grade Glioma patients with severe lymphopenia, as well as to test the effect of NT-I7 on the CD4 counts of patients in comparison to control participants. This study has both a Phase I and Pilot component.

开始日期2018-10-30

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

[+2]

100 项与 Cd4+淋巴细胞缺乏相关的临床结果

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100 项与 Cd4+淋巴细胞缺乏相关的转化医学

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0 项与 Cd4+淋巴细胞缺乏相关的专利（医药）

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156

项与 Cd4+淋巴细胞缺乏相关的文献（医药）

2025-12-01·Journal of Clinical Immunology

Abnormal Immune Profile in Individuals with Kabuki Syndrome

Article

作者: Sil, Debapratim ; Comel, Margot ; Andrau, Jean-Christophe ; Willems, Marjolaine ; Lozano, Claire ; Saad, Norma ; Djouad, Farida ; Apparailly, Florence ; Genevieve, David

OBJECTIVETo analyze the lymphocyte subsets in individuals with Kabuki syndrome for better characterizing the immunological phenotype of this rare congenital disorder.METHODSWe characterized the immunological profile including B-, T- and natural killer-cell subsets in a series (N = 18) of individuals with Kabuki syndrome.RESULTSAll 18 individuals underwent genetic analysis: 15 had a variant in KMT2D and 3 a variant in KDM6A. Eleven of the 18 individuals (61%) had recurrent infections and 9 (50%) respiratory infections. Three (17%) had autoimmune diseases. On immunological analysis, 6 (33%) had CD4 T-cell lymphopenia, which was preferentially associated with the KMT2D truncating variant (5/9 individuals). Eight of 18 individuals (44%) had a humoral deficiency and eight (44%) had B lymphopenia. We found abnormal distributions of T-cell subsets, especially a frequent decrease in recent thymic emigrant CD4 + naive T-cell count in 13/16 individuals (81%).CONCLUSIONThe immunological features of Kabuki syndrome showed variable immune disorders with CD4 + T-cell deficiency in one third of cases, which had not been previously reported. In particular, we found a reduction in recent thymic emigrant naïve CD4 + T-cell count in 13 of 16 individuals, representing a novel finding that had not previously been reported.

2025-04-01·Microbiology Spectrum

Effects of human immunoglobulin A on Cryptococcus neoformans morphology and gene expression

Article

作者: Zaragoza, Óscar ; Malacatus-Bravo, Claudia ; Cuesta, Isabel ; de Oliveira, Haroldo C. ; Pirofski, Liise-anne ; Sarai, Varona ; Rodrigues, Marcio L. ; Trevijano-Contador, Nuria

ABSTRACT Human IgM was previously shown to inhibit Titan-like cell formation of Cryptococcus neoformans , whereas IgG did not. Here, we conducted an in-depth analysis of the effect of normal human IgA on C. neoformans biology (strain H99) and compared it to that of IgG and IgM. We found that like IgM, IgA affected H99 cell size and morphology. The total size of cells cultured with IgA was significantly smaller at 24 h than cells cultured with IgM and IgG and comparable to IgM but smaller than IgG at 72 h. We also examined extracellular vesicle (EV) production and found that it was significantly reduced in cells cultured with IgA than the control, but the EVs were larger. To further probe the effect of IgA on H99, we performed expression profiling by RNAseq of H99 cells cultured with each immunoglobulin isotype and compared the results with IgA to those with IgM, IgG, and a control (PBS). These comparisons showed that cells cultured with IgA overexpressed genes related to cell rescue, defense, virulence, energy conservation, adapation to stress with CNAG_00735 (aldehyde dehydrogenase family seven member A1) being the most overexpressed, and repressed some genes related to vesicular transport, including CNAG_04306 (vesicle transporter SFT2B) and CNG_00063 (histone H3). Collectively, our findings suggest that the effects of IgA on cryptococcal biology deserve further investigation, as they reveal new insights into human host– C. neoformans interaction, which suggest that antibody responses may affect gene expression in C. neoformans . IMPORTANCE Profound CD4 T cell deficiency is associated with the development of cryptococcosis in HIV-infected individuals. However, perturbations in antibody immunity, including reduced levels of plasma IgA and IgM, have also been associated with cryptococcal disease status. While IgM has been studied in some detail, IgA has not. Here, we evaluated the effect of normal human IgA on Cryptococcus neoformans biology and morphology to expand knowledge of the role that it may play in cryptococcal pathogenesis.

2025-02-18·Infection and Immunity

The importance of Fcγ and C-type lectin receptors in host immune responses during Pneumocystis pneumonia

Article

作者: Bindzus, Marc ; Pellegrino, Madeline R. ; Limper, Andrew H. ; Schaefbauer, Kyle ; Kottom, Theodore J. ; Carmona, Eva M. ; Stelzig, Kimberly E.

ABSTRACTPneumocystis jirovecii pneumonia (PJP) remains a significant cause of morbidity and mortality during AIDS. In AIDS, the absence of CD4 immunity results in exuberant and often fatal PJP. In addition, organism clearance requires a balanced macrophage response since excessive inflammation promotes lung injury and respiratory failure. Corticosteroids given in addition to antibiotics significantly improve outcomes during PJP. However, concerns exist that corticosteroids further suppress immunity and increase co-infections. New strategies to promote killing and clearance of Pneumocystis while balancing lung inflammation are required. Prior studies have shown that innate immunity to Pneumocystis is mediated by C-type lectin receptors (CLRs) on macrophages and involves downstream CARD9 activation. CARD9 can be targeted by a novel specific small molecule inhibitor (BRD5529) that significantly reduces inflammatory signaling by macrophages. CARD9 serves as the central intracellular molecule through which Dectin-1, Dectin-2, Mincle, and other CLRs signal. Dectin-1 CLR is activated through its own intracytoplasmic domain, whereas other innate CLRs (e.g., Dectin-2 and Mincle) require interactions with a common Fc-gamma receptor (FcγR) accessory chain to mediate responses. We now observe that mice double deficient in both Dectin-1 and Fcer1g (which lack the FcγR gamma chain) exhibit markedly reduced organism clearance compared with Card9−/− infected animals. These mice also possess deficiencies in immunoglobulin (Ig) Fc receptors directly mediating antibody responses, further implicating altered humoral responses in Pneumocystis killing. We further demonstrate in the Pneumocystis pneumonia (PCP) mouse model that BRD5529 administration successfully suppresses inflammatory cytokines. Our data support that innate immune responses through the CLR-CARD9 axis and humoral response act together to mediate effective responses resulting in optimal organism killing and generation of host inflammatory responses. Furthermore, host lung inflammation during PCP may be successfully reduced with a novel CARD9 small molecule inhibitor. IMPORTANCEPneumocystis pneumonia (PCP) causes severe respiratory impairment in hosts with suppressed immunity, particularly those with CD4 deficiencies, such as HIV. In addition to lymphocytic immunity, both innate and humoral immunities also participate in host defense against Pneumocystis . In the current studies, we defined the relative roles of CLR receptor-mediated inflammation, as well as FcgR-related inflammation and clearance of Pneumocystis organisms. Our studies reveal important roles for CLR activities for inducing lung inflammation, which can be ameliorated with a novel small molecule inhibitor of the CARD9 adaptor protein that is necessary for CLR signaling. In contrast, FcgR has a dominant role in organism clearance, underscoring an integral role of humoral responses for the elimination of this infection.

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