Actualización en marcadores inmunológicos en el estudio de la infección por HIV: aportes desde el laboratorio clínico / Immunological markers in the study of HIV infection: contributions from the clinical laboratory. An update / Atualização em marcadores imunológicos no estudo da infecção pelo HIV: contribuições do laboratório clínico

Resumen Si bien la buena adherencia al tratamiento antirretroviral en la infección por el virus de la inmunodeficiencia humana (HIV por Human Immunodeficiency virus en inglés o VIH, por su sigla en español) demostró una sustancial mejoría clínica en las personas que viven con él, lograr el acceso al tratamiento continúa siendo un desafío en los tiempos que corren. Los estudios de laboratorio para diagnóstico y seguimiento de la infección por HIV se centran en estudios virológicos y recuento de linfocitos CD4+ y CD8+. Sin embargo, no se evalúa de forma detallada el perfil inmunológico de las personas que viven con HIV, ni la reconstitución inmune luego de recibido el tratamiento. Es por ello que el objetivo de esta revisión fue describir, por un lado, los diversos estudios realizados desde el laboratorio para el diagnóstico y seguimiento de la infección por HIV. Por otro lado, describir los aportes del laboratorio bioquímico en el estudio del perfil inmunológico de las personas que viven con HIV, el cual incluye desde determinaciones actualmente en uso, hasta nuevos biomarcadores inflamatorios solubles o de membrana celular, como así también las subpoblaciones linfocitarias. Dichos biomarcadores podrían ser herramientas valiosas como descriptores del estado inmunológico de las personas e, incluso, predictores de patologías asociadas a la infección por HIV.

Abstract Although a correct adherence rate to antiretroviral treatment in human immunodeficiency virus (HIV) infection reveals a substantial clinical improvement in people living with HIV, achieving access to treatment is still challenging. Laboratory studies for diagnosis and follow-up are mainly focused on virological status, CD4+ and CD8+ T cells counts. However, the immunological profile of people living with HIV is not evaluated in detail, neither is the immune reconstitution after treatment. Consequently, the aim of this review was is to describe, on the one hand, the studies carried out in the laboratory for the diagnosis and monitoring of HIV infection, and on the other hand, is to describe the contributions of the biochemical laboratory in the study of the immunological profile of people living with HIV. This study includes determinations currently in use, and the determination of new soluble or cell membrane inflammatory biomarkers, as well as T cell subsets. These biomarkers could be valuable tools as descriptors of the impervious state of people, and even predictors of pathologies associated with HIV infection.

Resumo Embora a boa adesão ao tratamento antirretroviral na infecção pelo vírus da imunodeficiência humana (HIV) tenha demonstrado melhora clínica substancial em pessoas que vivem com HIV, conseguir o acesso ao tratamento continua sendo um desafio nos momentos em que correm. Os estudos laboratoriais para diagnóstico e monitoramento da infecção pelo HIV concentram-se em estudos virológicos e contagem de linfócitos CD4+ e CD8+. No entanto, o perfil imunológico das pessoas que vivem com HIV não é avaliado detalhadamente, nem a reconstituição imunológica após o tratamento. É por isso que o objetivo desta revisão foi descrever, por um lado, os vários estudos realizados em laboratório para o diagnóstico e monitoramento da infecção pelo HIV. Por outro lado, descrever as contribuições do laboratório bioquímico no estudo do perfil imunológico de pessoas que vivem com HIV, que inclui desde determinações atualmente em uso, até novos biomarcadores inflamatórios solúveis ou de membrana celular, bem como subpopulações de linfócitos. Esses biomarcadores podem ser ferramentas valiosas como descritores do estado imunológico das pessoas e até mesmo como preditores de patologias associadas à infecção pelo HIV.

Incidence and risk factors of renal injury in human immunodeficiency virus infection/acquired immunodeficiency syndrome patients with poor immune reconstitution / 中华传染病杂志

Objective:To investigate the incidence and risk factors of renal injury in human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients with poor immune reconstitution.Methods:The HIV infection/AIDS patients with poor immune reconstitution who were visited Second Department of Infection of Hangzhou Xixi Hospital from January to December 2021 were enrolled. The clinical data and laboratory examinations of the patients were collected, and the relevant risk factors were analyzed by logistic regression.Results:Among 303 HIV infection/AIDS patients with poor immune reconstitution, 59(19.5%) patients had renal injury. Logistic regression analysis showed that hypertension (odds ratio ( OR)=0.200, 95% confidence interval (95% CI) 0.065 to 0.618, P=0.005), taking tenofovir ( OR=0.275, 95% CI 0.130 to 0.580, P=0.001), hypoproteinemia ( OR=1.045, 95% CI 1.006 to 1.086, P=0.022), and low CD4 + T lymphocytes level ( OR=1.009, 95% CI 1.003 to 1.014, P=0.001) were risk factors for renal injury. Conclusions:The incidence of renal injury in HIV infection/AIDS patients with poor immune reconstitution is high. Hypertension, taking tenofovir, hypoproteinemia, and low CD4 + T lymphocytes level are risk factors for renal injury in patients.

Investigation on the incidence of IRIS in HIV patients with TB infection and its relationship with Th17/Treg, CD4 + T lymphocyte levels / 中国医师杂志

Objective:To investigate the incidence of immune reconstitution inflammatory syndrome (IRIS) in patients with HIV (HIV) and tuberculosis (TB) infection, and analyze the relationship between Th17/Treg cytokines, CD4 + T lymphocytes and IRIS. Methods:HIV patients with TB infection admitted to Public Health Clinical Center of Chengdu from June 2020 to June 2022 were divided into IRIS group (31 cases) and non IRIS group (93 cases) according to whether IRIS occurred after highly active antiretroviral therapy (HAART). The Demography data, clinical data and laboratory indicators of the two groups were compared. Multivariate logistic regression analysis was conducted to investigate the influencing factors of IRIS in HIV patients with TB infection.Results:There was no significant difference in Demography data between the two groups ( P>0.05). There was a statistically significant difference in the history of opportunistic infection between the IRIS group and the non IRIS group (χ 2=5.194, P<0.05). The levels of HIV RNA, interleukin (IL)-17, and IL-23 in the IRIS group were higher than those in the non IRIS group (all P<0.05). The levels of the γ interferon (IFN- γ), the transforming growth factor-β (TGF- β) and baseline CD4 + T lymphocyte count were lower than those in the non IRIS group (all P<0.05). The results of multivariate logistic regression analysis showed that IL-17 ( OR: 1.266, 95% CI: 1.095-1.464), IL-23( OR: 1.384, 95% CI: 1.120-1.710), and TGF- β( OR: 0.589, 95% CI: 0.436-0.797) were influencing factors for the occurrence of IRIS in HIV patients with TB infection (all P<0.05). Conclusions:For patients with high IL-17 levels, high IL-23 levels, and low TGF- β level of HIV complicated with TB infection, clinical prevention and control should be carried out as soon as possible to prevent the occurrence of IRIS.

The Characteristics of T Lymphocyte Reconstitution after Haploid Hematopoietic Stem Cell Transplantation in SAA and Its Relationship with aGVHD / 中国实验血液学杂志

OBJECTIVE@#To investigate the recovery characteristics of T cell subsets in patients with severe aplastic anemia (SAA) who received haploid hematopoietic stem cell transplantation(HSCT) and its relationship with acute graft-versus-host disease(aGVHD).@*METHODS@#The clinical data of 29 SAA patients who received haploid hematopoietic stem cell transplantation in the department of hematology, Shanxi Bethune Hospital from June 2018 to January 2022 were retrospectively analyzed. The absolute counts of CD3+T, CD4+T, CD8+T lymphocytes and the ratio of CD4+T/CD8+T lymphocytes in all patients before transplantation, 14, 21, 30, 60, 90 and 120 days after transplantation were analyzed. The proportion of T lymphocytes was compared in the non-aGVHD group, the grade Ⅰ-Ⅱ aGVHD group and the grade III-IV aGVHD group.@*RESULTS@#The counts of all T cells in 27 patients were far below the normal level at 14 and 21 days after transplantation, but there was obvious heterogeneity. There was a certain relationship between T cell immune reconstitution and conditioning regimen, age, and immunosuppressive treatment before transplantation. CD3+T cells showed a steady upward trend at 30, 60, 90, and 120 days after transplantation, and returned to the normal levels at 120 days after transplantation; faster recovery of CD4+T cells was closely related to aGVHD, which was at 30, 60, 90, 120 days after transplantation showed a slow upward trend, and which was still far below the normal level of 120 days after transplantation. CD8+T cell counts began to recover at 14 and 21 days after transplantation, and the recovery was earlier than the CD4+T cells, and its recovery speed was rapid 30 and 60 days after transptantation, which showed an upward trend and exceeded the normal levels 90 days after transplantation. Since CD8+ T cells reconstituted quickly, while the CD4+ T cells reconstitution was slowly, which made the long-term CD4+T/CD8+T cell ratio after transplantation was inverted . Compared with the non-aGVHD group, the absolute counts of CD3+T, CD4+T, and CD8+T cells in the aGVHD group were significantly higher than those in the non-aGVHD group at each time period after transplantation. In the aGVHD group, grade Ⅲ-Ⅳ aGVHD occurred more frequently in the early post-transplantation period (within 14-21 days), the grade Ⅰ-Ⅱ aGVHD group mostly occurred within 30-90 days after transplantation, and CD3+T, CD4+T, CD8+T cell counts in the grade Ⅲ-Ⅳ aGVHD group were significantly higher than those in the grade Ⅰ-Ⅱ aGVHD group; and the greater the proportion of CD4+T, the more severe the degree of aGVHD.@*CONCLUSION@#The speed of T cell immune reconstitution after SAA haploid transplantation is different, which is related to the conditioning regimen, age, and immunosuppressive therapy before transplantation. The rapid recovery of CD4+ T cells is closely related to the occurrence of aGVHD.

Immune reconstitution after allogenic stem cell transplantation: An observational study in pediatric patients

Abstract Introduction The immune reconstitution (IR) after the allogenic hematopoietic stem cell transplantation (allo-HSCT) is a progressive process intrinsically correlated to the therapeutic success. It is essential to understand the interfering factors in IR to prevent the HSCT-related mortality. Methods We retrospectively evaluated the clinical outcomes, absolute lymphocyte counts (ALCs) and lymphocyte subtypes at different time-points of 111 pediatric patients with allogeneic HSCT for malignant and non-malignant diseases from 2013 to 2018. Results The ALCs gradually increased on D+30, D+100, and D+180 (medians 634/μL, 1022/μL and 1541/μL, respectively). On D+100, the CD3+CD8+ achieved the highest recovery rate (68%), followed by the CD16+CD56+ (47%), CD3+CD4+ (39%) and CD19+ (8%). The adequate ALC recovery was associated with age < 8 years, bone marrow grafts, myeloablative conditioning, non-use of serotherapy and non-haploidentical donors. The ALC and CD3+CD8+ on D+100 counts were higher in patients with the cytomegalovirus infection. The CD3+CD4+ recovery was associated with an age < 8 years, a non-malignant disease and a lower incidence of acute graft-versus-host disease ≥ grade 2. Furthermore, the ALC recovery on D+100 resulted in a higher overall survival, regardless of the disease type (HR 3.65, 1.05 - 12.71, p= 0.04). Conclusion Several factors influenced the IR after the allo-HSCT. The ALC ≥ 500/μL on D+100 was a simple IR predictor of survival, easily available to resource-limited centers.

Acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome: prevalence, main characteristics, and outcomes in a Brazilian center / Síndrome inflamatória de reconstituição imune da leucoencefalopatia multifocal progressiva associada à síndrome da imunodeficiência adquirida: prevalência, principais características e desfecho em um hospital brasileiro

Abstract Background Progressive multifocal leukoencephalopathy (PML) - immune reconstitution inflammatory syndrome (IRIS) in people living with HIV/AIDS (PLWHA) has been rarely described in low- and middle-income countries. Objective To describe the prevalence of PML-IRIS among PLWHA with PML and its main features in a tertiary hospital in Brazil. Methods We performed a retrospective cohort study. We included PLWHA with PML-IRIS patients admitted at Instituto de Infectologia Emílio Ribas, São Paulo, Brazil, between 2011 and 2021. We retrieved information on neurological manifestations, neuroimaging findings, treatments, and outcomes. Results We identified 11 (11.8%) PML-IRIS cases among 93 patients with definite PML. Eight (73%) cases were men and had a median (IQR) age of 41 (27-50) years. Seven (63.6%) patients developed unmasking PML-IRIS and 4 (36.4%) had paradoxical PML-IRIS. The median (IQR) time from initiation of combined antiretroviral therapy (cART) to IRIS diagnosis was 49 (30-70) days. Ten (90.9%) patients received corticosteroids. There were 4 (36%) in-hospital deaths and 3 were associated with hospital-acquired pneumonia. Among the 7 (64%) patients who survived, 5 (71.5%) had sequelae at discharge. One year after the PML-IRIS diagnosis, 6 (54.5%) patients were alive. Conclusion The prevalence of PML-IRIS was 11.8%. Most patients had unmasking PML-IRIS. In-hospital mortality and morbidity were high. One-year survival was similar to that described in some high-income countries.

Resumo Antecedentes A síndrome inflamatória de reconstituição imune (SIRI) da leucoencefalopatia multifocal progressiva (LEMP) em pessoas vivendo com HIV/Aids (PVHA) foi raramente descrita em países de baixa e média renda. Objetivo Descrever a prevalência da SIRI-LEMP- em PVHA com LEMP e suas principais características em um hospital no Brasil. Métodos Foi realizado um estudo de coorte retrospectivo. Incluímos PVHA com SIRI-LEMP admitidos no Instituto de Infectologia Emílio Ribas, São Paulo, Brasil, entre 2011 e 2021. Recuperamos informações sobre manifestações neurológicas, neuroimagem, tratamento e desfecho. Resultados Identificamos 11 (11,8%) casos de SIRI-LEMP entre 93 pacientes com LEMP definitiva. Oito (73%) casos eram homens e a mediana de idade (amplitude interquartile - AIQ) foi de 41 (27-50) anos. Sete (63,6%) pacientes desenvolveram SIRI-LEMP "desmascarada" e 4 (36,4%) casos apresentaram SIRI-LEMP "paradoxal". A mediana de tempo (AIQ) desde o início da terapia antirretroviral combinada (cART) até o diagnóstico de SIRI foi de 49 (30-70) dias. Dez (90,9%) pacientes receberam corticoide. Houve 4 (36%) óbitos intra-hospitalares e 3 foram associados à pneumonia hospitalar. Dos 7 (64%) pacientes que sobreviveram, 5 (71,5%) ficaram com sequelas na alta. Um ano após o diagnóstico de SIRI-LEMP, 6 (54,5%) pacientes estavam vivos. Conclusão A prevalência de SIRI-LEMP foi de 11,8%. A maioria dos pacientes apresentava SIRI-LEMP "desmascarada". A mortalidade e morbidade hospitalar foram altas. A sobrevida em 1 ano foi semelhante à descrita em alguns países de alta renda.

Strongyloides stercoralis en la médula ósea de una persona que vive con VIH: reporte de caso

Strongyloides stercoralis es un nemátodo que se caracteriza por causar infección intestinal, usualmente asintomática, en pacientes inmunocompetentes. Sin embargo, en aquellos que viven con VIH, y de acuerdo con su estado inmune, puede generar un síndrome de hiperinfección con complicaciones diversas por diseminación a diferentes órganos. Se presenta el caso de un paciente de 30 años con diagnóstico de novo de infección por el virus de la inmunodeficiencia humana, con documentación de enfermedad linfoproliferativa. En los estudios complementarios se documenta la presencia de Strongyloides stercoralis de manera inusual en la médula ósea. A pesar de contar con un recuento de linfocitos T CD4+ mayor a 400 células/ µL y de haberse iniciado el manejo para esta condición con ivermectina, el paciente fallece por un estado séptico asociado al síndrome de hiperinfección, por lo cual se considera que este es un caso inusitado que obliga al clínico a tener en cuenta la presencia del nemátodo en pacientes que viven con VIH.

Summary Strongyloides stercoralis is a nematode that is characterized by causing a usually asymptomatic intestinal infection in immunocompetent individuals. However, in patients living with HIV and depending on their immune status, it can generate a hyperinfection syndrome with various complications due to dissemination to different organs. We present the case of a 30-year-old patient with a de novo diagnosis of human immunodeficiency virus infection and lymphoproliferative disease. Within the laboratory workup, the presence of Strongyloides stercoralis was documented in the bone marrow. Despite having a CD4+ T lymphocyte count greater than 400 cells/microliter and having started treatment for this condition with ivermectin, the patient died due to a septic state associated with hyperinfection syndrome, which is why this is considered an unusual case that alerts the clinician to take into account the presence of the nematode in patients living with HIV.

Correlation between human immunodeficiency virus reservoir and poor immune reconstitution of human immunodeficiency virus/acquired immunodeficiency syndrome patients / 中华传染病杂志

Objective:To analyze the correlation between human immunodeficiency virus (HIV)-1 reservoir and poor immune reconstitution of HIV/acquired immunodeficiency syndrome (AIDS) patients, and to investigate the influence of HIV-1 reservoir on the immune reconstitution.Methods:Cross-sectional survey was conducted to measure HIV-1 RNA and T lymphocyte subsets from 219 patients with HIV/AIDS who had been treated with anti-retroviral therapy (ART) for more than two years with HIV RNA lower than the limit of detection. Among them, there are 195 patients from the Sixth People′s Hospital of Zhengzhou, 12 patients from Shangqiu Municipal Hospital and 12 patients from Zhoukou Infectious Diseases Hospital. Peripheral blood mononuclear cells (PBMC) were collected and HIV-1 DNA was detected. The measurement data of normal distribution were analyzed by two independent sample t-test. The measurement data of skewness distribution were analyzed by rank sum test. Spearman′s rank correlation was used for correlation analysis. Receiver operating characteristic curve (ROC) was used to predict the predictive value of occurrence of poor immune reconstitution AIDS patients. Results:There were 121 patients with poor immune reconstitution and 98 patients with healthy immune reconstitution. HIV-1 DNA was (2.50±0.52) copies/1×10 6 PBMC in the group with poor immune reconstitution, which was significantly higher than the healthy immune reconstitution group ((2.11±0.66) copies/1×10 6 PBMC, t=4.78, P<0.001). The CD4 + T lymphocyte counts in the group with poor immune reconstitution was 192(139, 227)/μL, which was lower than that in the healthy immune reconstitution group (573(457, 730)/μL). The difference was statistically significant ( Z=12.68, P<0.001). HIV-1 DNA was reversely correlated with CD4 + T lymphocyte counts and CD4 + /CD8 + T lymphocyte ratio (after adjusting the influence of age and ART time, r=-0.277 and -0.316, respectively, both P<0.001). The area of ROC curve for HIV-1 DNA to predict poor immune reconstitution was 0.679(95% confidence interval ( CI) 0.604 to 0.750). The HIV-1 DNA threshold value was 100 copies/1×10 6 PBMC with the sensitivity of 90.13% and specificity of 42.91%. The area of ROC curve of CD4 + /CD8 + T lymphocyte ratio to predict poor immune reconstitution was 0.905 (95% CI 0.863 to 0.942). The threshold value of CD4 + /CD8 + T lymphocyte ratio was 0.536 with the sensitivity of 77.68% and specificity of 89.84%. Conclusions:There is correlation between HIV-1 DNA and poor immune reconstitution in HIV/AIDS patients. The value of HIV-1 DNA higher than 100 copies/1×10 6 PBMC and CD4 + /CD8 + T lymphocyte ratio lower than 0.536 could be used as predictor of poor immune reconstitution.

Immune reconstitution in patients with allogeneic hematopoietic stem cell transplantation after CAR-T immunotherapy / 中华检验医学杂志

Objective:To study the performance of immune reconstitution in patients with chimeric antigen receptor (CAR)-T cell immunotherapy bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 61 patients with acute B lymphocytic leukemia (B-ALL) who received CAR-T cell bridging allo-HSCT in Beijing Lu Daopei Hospital from August 2018 to December 2021 were enrolled, and the clinical medical records of the above patients were retrospectively analyzed. The average age was 14 (7, 30) years old, including 39 males and 22 females. 32 patients were treated with CAR-T cell immunotherapy(CAR-T Group) and 29 didn't with CAR-T cell immunotherapy(non-CAR-T group). The follow-up period was 561 (235,784) days. Multicolor flow cytometry was used to detect the peripheral blood lymphocyte subsets, i.e. total lymphocytes, T lymphocytes, helper T cells, cytotoxic T cells, B lymphocytes, NK cells, and Treg cell counts before transplantation and 1, 2, 3, 6, 8, 10, and 12 months after transplantation, to evaluate the immune reconstitution performance post allo-HSCT.Results:Serum globulin before transplantation: The IgA level in the CAR-T group was 0.18 (0.06, 0.49) g/L, which was lower than that of 1.03 (0.63, 1.56) g/L in the non-CAR-T group ( U=103.5, P<0.001). The IgG level in the CAR-T group was 5.54 (4.04, 7.09) g/L, lower than that of 6.78 (5.27, 9.26) g/L in the non-CAR-T group, ( U=1 298.5, P=0.017), and the IgM level in the CAR-T group was 0.18 (0.05, 0.30) g/L, lower than that of 0.40 (0.26, 0.71) g/L in the non-CAR-T group ( U=166.0, P<0.001). In the CAR-T group before transplantation, the absolute count of total lymphocyte in peripheral blood was 833.00 (335.00, 1 727.50) /μl, lower than that of 1 052.00 (545.75, 1 812.50) /μl in the non-CAR-T group ( U=404.0, P<0.001). The absolute count of T lymphocyte in the CAR-T group before transplantation was 686.00 (233.00, 1 307.00)/μl, lower than that of 860.00 (391.00, 1 419.75) /μl in the non-CAR-T group ( U=406.0, P<0.001). The absolute count of helper T lymphocytes in the CAR-T group was 146.00 (40.50, 327.50) /μl, lower than that of 162.50 (66.00, 384.75) /μl in the non-CAR-T group ( U=494.0, P=0.002). The absolute count of cytotoxic T lymphocytes in the CAR-T group was 343.00 (56.50, 924.00) /μl, lower than that of 478.00 (143.50, 992.25) /μl in the non-CAR-T group ( U=483.5, P=0.001). The absolute count of B lymphocytes in CAR-T group was 22.00 (6.00, 186.00) /μl, lower than that of 33.00 (8.00, 220.00) /μl in the non-CAR-T group ( U=498.0, P=0.002). And when two groups of patients were monitored after transplantation, there was no statistical difference in absolute cell counts of each immune cell subpopulation( P>0.05). Comparing the clinical features of the two groups, the pre-transplant history of the CAR-T group was 981.00 (368.50, 1 514.75) d, longer than that of 323.00 (167.50, 450.50) d in the non-CAR-T group ( U=263.0, P=0.004). The dose of rabbit anti-human thymic immunoglobulin (ATG) in the pretreatment protocol of patients in the CAR-T group was 5.00 (5.00, 7.50) mg/Kg, lower than that of 7.00 (5.00, 7.50) mg/kg in the non-CAR-T group ( U=288.5, P=0.018). The infusion dose of CD34 +cells in the CAR-T group was 5.91 (4.23, 6.02) ×10 6/kg, higher than that of 4.51 (4.00, 5.93)×10 6/kg in the non-CAR-T group ( U=291.0, P=0.012). The duration of the application of cyclosporine after transplantation in the CAR-T group was 167.00 (119.25, 299.50) d, which was shorter than that of 197.00 (102.50, 450.50) d in the non-CAR-T group ( U=421.0, P=0.001). Conclusions:For patients in CAR-T group with low immune function before transplantation, it may be possible to make them comparable to non-CAR-T group in immune reconstitution state by reducing the dose of pretreatment ATG, increasing the counts of CD34 + cells infusion in the graft, and discontinuing cyclosporine as soon as possible after transplantation.

Guillain-Barré syndrome spectrum as manifestation of HIV-related immune reconstitution inflammatory syndrome: case report and literature review

ABSTRACT A 34-year-old man presented with a history of 21-days of gait unsteadiness and diplopia. Ten days before presentation, he developed limb weakness and in the last three days reduced consciousness. HIV infection was diagnosed three months ago (CD4+ = 160 cells/ mm3; viral load HIV-1 = 144.000 copies/mL), and antiretroviral therapy was initiated. Impaired consciousness, ophthalmoplegia, limb weakness, ataxia, areflexia, and Babinskys sign were noted. At that moment, CD4+ count was 372 cells/mm 3 and viral load HIV-1 < 50 copies/mL. The clinical, laboratory and neurophysiological findings suggest overlapping Guillain-Barré syndrome (GBS) and Bickerstaff brainstem encephalitis as manifestation of HIV-related immune reconstitution inflammatory syndrome (IRIS). Here, we review and discuss 7 cases (including the present report) of GBS spectrum as manifestation of HIV-related IRIS.

Progress of immune cell reconstitution after allogeneic hematopoietic stem cell transplantation / 国际儿科学杂志

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective cure for many hematologic and non-hematologic diseases.However, infection morbidity and mortality remain high after allo-HSCT, which is closely related to the recovery of immune cell subsets.The detailed information on the recovery of natural killer(NK), T and B cell subsets can better predict and regulate the occurrence of adverse events.This article will review the current rules, influencing factors and the relationship between the outcome and the immune reconstitution of NK cells, T cells and B cells after hematopoietic stem cell transplantation.

Postinfectious inflammatory response syndrome in patients with cryptococcal meningitis / 中华神经科杂志

Cryptococcal meningitis is a common fungal meningitis that may present with an abnormal immune response during effective antifungal therapy and is called immune reconstitution inflammatory syndrome in human immunodeficiency virus (HIV)-infected patients. Similar phenomenon can also be seen in non-HIV patients with normal immune function in the past. Paradoxical clinical and/or imaging deterioration occurs due to strong immune response during treatment, which is called post-infectious inflammatory response syndrome. At present, it has not attracted attention. This complication is an important cause of poor prognosis in non-HIV patients. Early identification and treatment of post-infectious inflammatory response syndrome is of great significance. This article will review its possible pathogenesis, clinical manifestations, imaging characteristics, risk prediction, diagnosis, treatment and prognosis.

The therapeutics and management of cryptococcus-related immune reconstitution inflammatory syndrome in AIDS patients / 中华临床感染病杂志

Acquired immune deficiency syndrome (AIDS) can cause various opportunistic infections clinically due to severe defects in the body’s cellular immune function. Cryptococcosis is a common serious opportunistic infection in AIDS patients. With the promotion and popularization of high activity antiretroviral therapy (HAART) programs worldwide, the mortality rate of AIDS-related cryptococcosis has been significantly decreased. After initiating antiviral therapy, some patients experienced recurrence and aggravation of clinical symptoms during anti-cryptococcal treatment. The body has an inflammatory response to the excessive immune regulation of cryptococcal antigens, which is called cryptococcus-related immune reconstitution inflammatory syndrome (C-IRIS). C-IRIS seriously affects the quality of life and prognosis of patients. This article reviews the clinical features, pathogenesis and the latest treatment and management strategies of C-IRIS in AIDS patients.

Clinical manifestation and treatment of ocular immune reconstitution inflammatory response syndrome in acquired immunodeficiency syndrome patients with cytomegalovirus retinitis / 中华实验眼科杂志

Objective:To investigate the ocular characteristics and treatment prognosis of ocular immune reconstruction inflammatory syndrome (IRIS) in patients with cytomegalovirus retinitis (CMVR) complicated with acquired immunodeficiency syndrome (AIDS).Methods:A serial case-observational study was conducted.Seventeen eyes from 15 male 21-to 43-year-old AIDS patients combined with CMVR, who were diagnosed with IRIS at Beijing You'an Hospital, Capital Medical University from February 2016 to December 2018 were included.The best corrected visual acuity (BCVA) of patients was recorded, and the intraocular pressure and anterior segment was measured with a non-contact tonometer and a slit-lamp microscope, respectively.The ocular fundus was observed by fundus photography and optical coherence tomography (OCT). Reverse transcription polymerase chain reaction was used to measure the cytomegalovirus deoxyribonucleic acid (CMV-DNA) content in the aqueous humor during the occurrence of IRIS.The flow cytometry was employed to determine the peripheral blood CD4 + T lymphocyte count before highly active antiretroviral therapy (HAART) and during the occurrence of IRIS.All patients were followed for 3 to 25 months, with an average of 15 months.The HAART time of patients was 17 to 104 days, with an average of (66.1±27.4) days.Patients with anterior segment inflammatory reactions were given the anti-inflammatory and mydriatic treatment.Patients with severe vitreous opacity were intravitreally injected with 4 mg of triamcinolone.Patients with macular edema were given 0.5 mg intravitreal injection of conbercept.The study adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Beijing You'an Hospital, Capital Medical University (No.[2017]11). Written informed consent was obtained from each patient prior to any examination. Results:Anterior segment inflammation (Tyndall effect, KP, post-iris adhesion) was found in 9 eyes, vitreous opacities to varying degrees in 11 eyes, and macular edema in 2 eyes.The CMV-DNA content was negative (<500 copies/ml) in 15 eyes.The CD4 + T lymphocyte count in peripheral blood during IRIS was 67 (51, 99) cells/μl, which was significantly higher than 17(6, 20) cells/μl before HAART treatment ( Z=-4.48, P<0.01). Two of the 15 AIDS patients had tuberculosis.The BCVA of the patients was improved from 0.30 (0.10, 0.55) before treatment to 0.50 (0.35, 0.60) after treatment, and the difference was statistically significant ( Z=-2.34, P=0.019). Conclusions:The anterior and posterior segment may be involved in IRIS patients with AIDS and CMVR, and the corresponding ocular treatment is effective.

Histoplasmosis diseminada asociada a síndrome de reconstitución inmune en un paciente con virus de la inmunodeficiencia humana / Disseminated histoplasmosis associated to immune reconstitution syndrome in a patient with human immunodeficiency virus

Introducción: La histoplasmosis es una micosis profunda o sistémica causada por un hongo dimórfico que se puede diseminar principalmente en pacientes con inmunosupresión, como los que tienen diagnóstico de virus de la inmunodeficiencia humana. El síndrome de reconstitución inmune consiste en un empeoramiento paradójico de una condición conocida o de nueva aparición después del inicio de la terapia antirretroviral. Objetivo: Describir un caso de histoplasmosis diseminada asociada a síndrome de reconstitución inmune en un paciente con infección por virus de la inmunodeficiencia humana. Caso clínico: Paciente masculino de 32 años con diagnóstico de infección por virus de la inmunodeficiencia humana, con cuadro clínico de tres semanas de evolución. Este cuadro inició posterior al comienzo de la terapia antirretroviral, que consistió en pápulo-nódulos umbilicados diseminados, con compromiso pulmonar; además, tenía histopatología y cultivo positivos para Histoplasma capsulatum sl. y prueba de antigenuria para histoplasma también positiva. Se consideró un diagnóstico de histoplasmosis diseminada con presentación cutánea, fue la expresión de un síndrome de reconstitución inmune por desenmascaramiento. Se inició manejo con anfotericina B liposomal y se mantuvo la terapia antirretroviral; posteriormente se continuó el tratamiento con itraconazol durante 12 meses con mejoría de las lesiones. Conclusiones: El diagnóstico clínico, histopatológico y microbiológico fue oportuno; el paciente presentó una adecuada respuesta al tratamiento. Esta es una micosis curable e incluso prevenible, si se diagnostica a tiempo, se inicia tratamiento precoz y se mantiene la terapia retroviral(AU)

Introduction: Histoplasmosis is a deep or systemic mycosis caused by a dimorphic fungus which may disseminate mainly in immunocompromised patients, such as those diagnosed with human immunodeficiency virus. Immune reconstitution syndrome is a paradoxical worsening of a known condition or a condition appearing after the start of antiretroviral therapy. Objective: Describe a case of disseminated histoplasmosis associated to immune reconstitution syndrome in a patient with human immunodeficiency virus infection. Case report: A case is presented of a male 32-year-old patient diagnosed with human immunodeficiency virus with a clinical status of three weeks' evolution. The current status developed after the start of antiretroviral therapy. It consisted in disseminated umbilicated papular nodules with pulmonary involvement, as well as positive Histoplasma capsulatum sl. histopathology and culture, and a positive histoplasma antigen test. A diagnosis of disseminated histoplasmosis with a cutaneous presentation was considered. It was the expression of immune reconstitution syndrome by unmasking. Treatment was started with liposomal amphotericin B, maintaining the antiretroviral therapy. Management was then continued with itraconazole for 12 months with improvement of the lesions. Conclusions: Timely clinical, histopathological and microbiological diagnosis was performed. The patient displayed an adequate response to treatment. This mycosis is curable and even preventable when a diagnosis is made in time, treatment is started early and the retroviral therapy is maintained(AU)

Immune reconstitution inflammatory syndrome in non human immunodeficiency viruses children on anti tubercular treatment

The term IRIS is almost solely used in human immunodeficiency virus seropositive patients who initiated anti-retroviral therapy (ART), the term paradoxical reaction is generally used to describe a clinical worsening of tuberculosis disease after the initiation of antituberculosis treatment. Distinguishing this paradoxical reaction (PR) from disease progression or treatment failure is an important issue in CNS tuberculosis management. Thus, one must keep a watch for neurological deterioration in a child with Central nervous system tuberculosis (CNS TB). We are presenting a case of a non-Human immunodeficiency virus (HIV) child who developed TB-IRIS while on anti-tubercular drugs, who subsequently responded to steroids along with continuation of antitubercular treatment (ATT).

Tuberculosis y síndrome inflamatorio de reconstitución inmunológica. Caso pediátrico / Tuberculosis and immune reconstitution inflammatory syndrome. Pediatric case

La tuberculosis es una enfermedad muy frecuente en nuestro medio. A pesar de que la detección precoz y el tratamiento adecuado logran la curación en la mayoría de los pacientes, la dificultad en el diagnóstico, el abandono del tratamiento y la aparición de resistencia a los fármacos tradicionales generan que, en la actualidad, continúe siendo un importante problema de salud pública. En la Argentina, la tasa de morbilidad es de 25/100 000 habitantes, con un leve aumento en la mortalidad.Se presenta el caso de una paciente pediátrica con tuberculosis, que tuvo múltiples complicaciones asociadas a la enfermedad y a su tratamiento, entre las cuales se incluye el síndrome in-flamatorio de reconstitución inmunológica, también conocido como reacción paradojal al tratamiento antituberculoso. Este representa una consecuencia clínica adversa al restablecimien-to de la inmunidad en el paciente que padece una infección sistémica grave, como la tuberculosis miliar.

Tuberculosis is a very frequent disease in our environment. Although early detection and adequate treatment achieve cure in most patients, the difficulty in diagnosis, the abandonment of treatment and the appearance of resistance to traditional drugs generate that at present it continues to represent an im-portant public health problem. In Argentina, the morbidity rate is 25/100,000 inhabitants, with a slight increase in mortality.We present the case of a pediatric patient with tuberculosis and multiple complications associated with the disease and its treatment. One of these complications was the immune re-constitution inflammatory syndrome or paradoxical reaction to antituberculosis treatment. It represents an adverse clinical con-sequence of the restoration of immunity in the patient suffering from a serious systemic infection such as miliary tuberculosis.

Altered T cell and monocyte subsets in prolonged immune reconstitution inflammatory syndrome related with DRESS (drug reaction with eosinophilia and systemic symptoms)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction involving various internal organs. Flare-ups after recovery from the initial presentation of DRESS are caused by relapse of drug-induced T-cell-mediated reactions. However, the specific underlying mechanism is unclear. Here, we report a case of a 60-year-old man with allopurinol-induced DRESS who suffered recurrent episodes of generalized rash with eosinophilia, which mimicked immune reconstitution inflammatory syndrome. Analysis of immunological profiles revealed that the percentages of T lymphocytes and regulatory T cells in the patient with DRESS were higher than those in healthy controls. In addition, there was a notable change in the subtype of monocytes in the patient with DRESS; the percentage of nonclassical monocytes increased, whereas that of classical monocytes decreased. Upon viral infection, nonclassical monocytes exhibited strong pro-inflammatory properties that skewed the immune response toward a Th2 profile, which was associated with persistent flare-ups of DRESS. Taken together, the results increase our understanding of the pathogenesis of DRESS as they suggest that expansion of nonclassical monocytes and Th2 cells drives disease pathogenesis.

Prevalence, Clinical Manifestations and Predictors of Immune Reconstitution Inflammatory Syndrome among HIV-Infected Patients in Malaysia Infectious Disease Centre: A Retrospective Study

@#Introduction: Immune reconstitution inflammatory syndrome (IRIS) is paradoxical clinical deterioration experienced by some HIV-infected patients in response to antiretroviral therapy (ART). There is still limited published data on IRIS from this region including Malaysia. This study aimed to determine IRIS prevalence, clinical manifestations and possible predictors among HIV-infected patients in an infectious disease centre in Peninsular Malaysia. Method: This retrospective study was conducted in Hospital Sungai Buloh involving secondary data of 256 HIV-infected patients who were initiated on ART in the year 2017. Medical record of each patient was reviewed for up to 12 months following ART initiation to identify IRIS diagnosis which was made by the treating physician. Relevant clinical and laboratory information were retrieved from hospital electronic database. Results: IRIS has occurred in 17.6% of patients. Infections by Mycobacterium tuberculosis (53.3%), Pneumocystis jirovecii (11.1%) and Talaromyces marneffei (6.6%) were the commonest three aetiologies of IRIS. Subacute lupus erythematosus was the only non-infectious IRIS identified. Baseline HIV viral load, CD4+ T-cell count and haemoglobin level between IRIS and non-IRIS patients were significantly different. Risk of developing IRIS was increased seven times in patients with CD4+ T-cell count < 100 cells/µL and four times in patients with HIV RNA viral load > 5.5 log10 copies/ml prior to ART initiation. Conclusion: Mycobacterium tuberculosis infections were the highest IRIS manifestation. Although rare, non-infectious IRIS does occur and should be part of the differential diagnosis. Patients with positive predictors should be appropriately monitored for possible IRIS development once initiated on ART.

Predictive value of baseline CD4+ Cell Counts and CD4/CD8 ratio in immune reconstitution in HIV/AIDS patients receiving highly effective antiretroviral therapy / 公共卫生与预防医学

Objective To explore the predictive value of baseline CD4+ cell counts and CD4/CD8 ratio in immune reconstitution among HIV/AIDS patients receiving highly effective antiretroviral therapy (HAART). Methods A total of 90 HIV/AIDS patients who had received over 24 months of HAART regimen and had viral road s) (s) (200~500 cells/μl) and immunological responders (IRs) (>500 cells/μl) according to the CD4 cell counts after two-year HAART regimen. The characteristics and dynamic CD4+ cell counts among the three groups were compared, and the factors of immune reconstitution were analyzed. Results The CD4+ cell counts in the immunological responders (IRs) were significantly higher than those in the immunological non-responders (INRs) and immunological inadequate responders (IIRs) (P+ cells reached the highest predictive value at 1 year of HAART. Conclusion Our findings suggested that early initiation of HAART could reduce the failure of immune reconstitution. The combination of baseline CD4+ cell counts and baseline CD4/CD8 ratio may serve as a valid predictor of immune reconstitution prognosis after HAART.