According to current evidence, human immunodeficiency virus (HIV)-infected patients who have undergone treatment with antiretroviral therapy are at greater risk of developing herpes zoster, not when they are severely immunocompromised, but, paradoxically, when their immune system is recovering. This is a manifestation of the immune reconstitution inflammatory syndrome (IRIS). Here we report on a case of IRIS, presented as herpes zoster in a HIV-infected patient after undergoing highly active antiretroviral therapy (HAART).
Antiretroviral Therapy, Highly Active ; Herpes Zoster ; HIV ; Humans ; Immune Reconstitution Inflammatory Syndrome ; Immune System ; Iris

Opportunistic infections (OIs) are the major cause of morbidity and mortality in HIV-infected patients. The incidences of many OIs are decreasing because of advances in HIV-related therapy. These decreases have been attributed to successful OI prophylaxis and the use of potent antiretroviral therapy (ART). ART has reduced the incidence of OIs and has extended the patients' life expectancy substantially. ART is the most effective approach to prevent OIs. However, HIV-infected patients continue to develop OIs. This occurs because many patients unaware of their HIV status until they present with an OI, and also because certain patients seek medical attention at a later stage during the course of disease. OIs also still occur after the patient has started ART, in the setting of treatment failure or immune reconstitution syndrome. Therefore, OIs will continue to cause substantial morbidity and mortality in patients with HIV infection, even among persons who are receiving ART. In this review, we focus on primary and secondary prophylaxis as well as the treatment of the most frequent OIs in HIV-infected patients.
HIV ; HIV Infections ; Humans ; Immune Reconstitution Inflammatory Syndrome ; Incidence ; Life Expectancy ; Mortality ; Opportunistic Infections* ; Treatment Failure

Tuberculosis is one of the most common opportunistic diseases in human immunodeficiency virus (HIV)-infected patients in Korea, and extra-pulmonary infections are frequent in these patients. Cutaneous miliary tuberculosis is a rare form of tuberculosis that presents as a papulopustular eruption and hematogenous dissemination of Mycobacterium tuberculosis to multiple organs. This has been reported in patients with progressive HIV infection. We report the first case of cutaneous miliary tuberculosis that developed as a manifestation of immune reconstitution inflammatory syndrome (IRIS) after initiating antiretroviral therapy (ART).
HIV ; HIV Infections ; Humans ; Immune Reconstitution Inflammatory Syndrome* ; Korea ; Mycobacterium tuberculosis ; Skin ; Tuberculosis ; Tuberculosis, Miliary*

Immune reconstitution syndrome (IRS) in HIV-infected patients is an adverse consequence of the restoration of pathogen-specific immune responses during the initial months of highly active antiretroviral treatment(HAART). Previously subclinical infections are unmasked or pre-existing opportunistic infections clinically deteriorate as host immunopathological inflammatory responses are switched on. While the eye is the area where Cytomegalovirus(CMV)-associated IRS occurs most often in patients with AIDS, it also can present with intestinal or pulmonary involvement. We present a case report of an HIV-infected patient in whom CMV enterocolitis and jejunal perforation developed after HAART.
Antiretroviral Therapy, Highly Active ; Asymptomatic Infections ; Cytomegalovirus* ; Enterocolitis* ; Humans ; Immune Reconstitution Inflammatory Syndrome ; Opportunistic Infections

Immune reconstitution syndrome (IRS) in HIV-infected patients is an adverse consequence of the restoration of pathogen-specific immune responses during the initial months of highly active antiretroviral treatment(HAART). Previously subclinical infections are unmasked or pre-existing opportunistic infections clinically deteriorate as host immunopathological inflammatory responses are switched on. While the eye is the area where Cytomegalovirus(CMV)-associated IRS occurs most often in patients with AIDS, it also can present with intestinal or pulmonary involvement. We present a case report of an HIV-infected patient in whom CMV enterocolitis and jejunal perforation developed after HAART.
Antiretroviral Therapy, Highly Active ; Asymptomatic Infections ; Cytomegalovirus* ; Enterocolitis* ; Humans ; Immune Reconstitution Inflammatory Syndrome ; Opportunistic Infections

Severe combined immunodeficiency disease (SCID) is a group of rare congenital diseases characterized by severe deficiencies in T lymphocyte counts and/or function. The recurrent, persistent and severe infections are its clinical manifestations. Neonatal screening and immune system reconstruction would improve the prognosis of SCID children. Newborn screening programs based on T-cell receptor excision circles (TRECs) quantitative detection have been carried out in clinical practice, however, the methods still have some limitations. Other new methods such as mass spectrometry and T lymphocyte-specific biomarker assays are still under investigation. Hematopoietic stem cell transplantation and gene therapy are the two main methods for reconstructing immune function in SCID children. Through improving the success rate of transplantation and the long-term safety and stability of viral vectors, some achievements have been made by many centers already. However, large-scale prospective studies are needed for evaluation of the long-term efficacy. In this article, the recent progress in newborn screening and immune reconstitution of SCID is reviewed.
Humans ; Immune Reconstitution ; Infant, Newborn ; Neonatal Screening ; trends ; Prospective Studies ; Severe Combined Immunodeficiency ; therapy ; T-Lymphocytes

Highly active antiretroviral therapy (HAART), which restores specific immune responses, may paradoxically cause an inflammatory reaction known as immune reconstitution inflammatory syndrome (IRIS). We report a patient with acquired immune deficiency syndrome, who presented Molluscum contagiosum as IRIS after HAART, the first case in Korea.
Acquired Immunodeficiency Syndrome ; Antiretroviral Therapy, Highly Active ; HIV ; Humans ; Immune Reconstitution Inflammatory Syndrome ; Iris ; Korea ; Molluscum Contagiosum ; Skin ; Skin Manifestations

OBJECTIVE: To investigate the effects of cytomegalovirus (CMV) DNA load on immune reconstitution and clinical outcomes of patients after unrelated cord blood transplantation (UCBT). METHODS: Eight-color flow cytometry was used to dynamically monitor the changes of peripheral blood lymphocyte subsets of 41 patients at one year after UCBT, and 10 healthy volunteers were enroled as controls. Patients were divided into two groups according to the DNA load of CMV (DNA copies <1000/ml and DNA copies ≥1000/ml). Comparative analyse of the effect of CMV DNA load on lymphocyte subsets and transplantation outcomes were carried out after transplantation. RESULTS: The high CMV DNA load group showed a faster and expanded T cell reconstitution, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.38×10 /L vs 0.25×10 /L, P=0.015 and 2.53×10 /L vs 1.36×10 /L, P=0.006, respectively). Further analysis of T cell subsets suggested that CD8 T cells presented a higher and faster recovery in the high DNA load group, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.20×10 /L vs 0.10×10 /L, P=0.038 and 1.62×10 /L vs 0.68×10 /L, P=0.003, respectively). In addition, there were no significant differences in levels of B cells, regulatory B cells and NK cells between the two groups. Outcomes after one- and a-half-year transplantation showed that there were no significant difference in relapse, non-relapse mortality and overall survival between the high and the low DNA load groups (7.7% vs 7.5%) (P=0.900) (15.4% vs 21.4%) (P=0.686) and (76.9% vs 78.6%) (P=0.889) respectively. CONCLUSION The high CMV DNA load induces a faster and long-lasting expansion of T cells, mainly as the expansion of CD8 T cells after UCBT. Besides, under the current pre-emptive treatment of CMV, the high CMV DNA load does not affect the early survival of patients with acute myeloid leukemia after UCBT.
CD8-Positive T-Lymphocytes ; Cord Blood Stem Cell Transplantation ; Cytomegalovirus ; DNA ; Hematopoietic Stem Cell Transplantation ; Humans ; Immune Reconstitution

OBJECTIVE: To investigate whether interleukin-12 (IL-12) over-expression in malignant melanoma B16 cells affects the expression level of programmed death-1 (PD-1) on T cells in mice during immune microenvironment reconstruction. METHODS: B16 cells were transfected with an IL-12 expression lentiviral vector, and IL-12 over-expression in the cells was verified qPCR and ELISA. Plate cloning assay was used to compare the cell proliferation activity between B16 cells and B16/IL-12 cells. The expression of IL-12 protein in B16/IL-12 cells-derived tumor tissue were detected by ELISA. C57BL/6 mice were inoculated with B16 cells or B16/IL-12 cells, and 14 days later the proportion of T cells with high expression of PD-1 in the tumor-draining lymph nodes was detected by flow cytometry. Mouse models of immune reconstitution established by 650 cGy X-ray radiation were inoculated with B16 (B16+RT group) or B16/IL-12 (B16/IL-12+RT group) cells, with the mice without X-ray radiation prior to B16 cell inoculation as controls. Tumor growth in the mice was recorded at different time points, and on day 14, flow cytometry was performed to detect the proportion of T cells with high PD-1 expression in the tumor-draining lymph nodes and in the tumor tissue. RESULTS: B16 cells infected with the IL-12-overexpressing lentiviral vector showed significantly increased mRNA and protein levels of IL-12 ( < 0.001) without obvious changes in cell viability (>0.05). B16/IL-12 cells expressed higher levels of IL-12 than B16 cells ( < 0.01). In the tumor-bearing mouse models, the proportion of CD4 PD-1 T cells was significantly lower in B16/IL-12 group than in B16 group ( < 0.01). In the mice with X-ray radiation-induced immune reconstitution, PD-1 expressions on CD4 T cells ( < 0.05) and CD8+ T cells ( < 0.01) were significantly higher in B16+ RT group than in the control mice and in B16/IL-12+RT group ( < 0.01 or 0.001); the tumors grew more slowly in B16/IL-12+RT group than in B16 + RT group ( < 0.001). CONCLUSIONS During immune microenvironment reconstruction, overexpression IL-12 in the tumor microenvironment can reduce the percentage of PD-1 T cells and suppress the growth of malignant melanoma in mice.
Animals ; CD8-Positive T-Lymphocytes ; Cell Line, Tumor ; Immune Reconstitution ; Interleukin-12 ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Tumor Microenvironment

Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q₁, Q₃) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3⁺T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4⁺T/CD8⁺T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8⁺T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8⁺T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.
Male ; Humans ; Child ; Female ; Immune Reconstitution ; Retrospective Studies ; Cytomegalovirus Infections ; Hematopoietic Stem Cell Transplantation/adverse effects* ; CD8-Positive T-Lymphocytes