Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection

ABSTRACT Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)

Abstract Introduction The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. Patients and methods This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. Results Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. Conclusion The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

Chronic mucocutaneous candidiasis associated with paracoccidioidomycosis in a patient with mannose receptor deficiency: First case reported in the literature

Abstract We describe the first report of a patient with chronic mucocutaneous candidiasis associated with disseminated and recurrent paracoccidioidomycosis. The investigation demonstrated that the patient had a mannose receptor deficiency, which would explain the patient's susceptibility to chronic infection by Candida spp. and systemic infection by paracoccidioidomycosis. Mannose receptors are responsible for an important link between macrophages and fungal cells during phagocytosis. Deficiency of this receptor could explain the susceptibility to both fungal species, suggesting the impediment of the phagocytosis of these fungi in our patient.

Cellular immunodeficiency related to chronic dermatophytosis in a patient with Schistosoma mansoni infection: can schistosomiasis induce immunodeficiency?

Abstract: Here, we describe a case of hepatosplenic schistosomiasis that progressed to widespread persistent dermatophytosis. Significant T and B lymphocytopenia was confirmed. T-cell deficit is associated with increased susceptibility to fungal infections of skin and mucous membranes. The accumulation of a large amount of blood cells in the spleen could have played a crucial role in the development of lymphocytopenia in the present case. Alternatively, the schistosomiasis-induced increase in prostaglandin E2 levels could have inhibited the production of interferon-γ, a cytokine fundamental to fungal resistance. This case shows the potential of hepatosplenic schistosomiasis to impair the immune response.

Caracterização das células produtoras de citocinas envolvidas na resposta imunológica celular em pacientes portadores de candidíase mucocutânea crônica / Characterization of the cytokines producing cells involved in the cellular imune response of chronic mucocutaneous candidiasis patients

Candidíase Mucocutânea crônica é uma imunodeficiência primária que tem como característica a suscetibilidade a infecções em mucosas, no tecido cutâneo e em seus anexos por Candida, na maioria das vezes por Candida albicans. Um defeito na resposta a Candida, mediada por células tem sido documentada em portadores de CMC. Alguns poucos trabalhos sugerem que os pacientes com CMC apresentem uma alteração na produção de citocinas em resposta a Candida. Nós estudamos a produção de citocinas pelas células T de quinze pacientes com CMC. Avaliamos a produção de IL-2,IL-4,IL-10 e IFN-y em ensaios de linfoproliferação estimulados com antígenos de Candida, Toxóide tetânico(TT) e também avaliamos a produção de citocinas destas células,nestas mesmas condições,quando imunomoduladas com IL-2,IL-12 e anticorpo anti-IL-10. Para obter esta analise, utilizamos ensaios de citocina intracelular e avaliação por citometria de fluxo / Chronic Mucocutaneous Candidiasis (CMC) is a primary immune deficiency presenting as an inability to clear fungal infections and consequently as persistent and recurrent infections of the skin and mucous membranes with yeasts, mostly Candida albicans. Some works suggested that CMC patients may exhibit altered cytokine production in response to Candida. We studied the citokines prodution of fifteen CMC patients. We evaluated the T cell prodution of IL-2, IL-4,IL-10 and IFN-y by trials of linfoproliferation by Candida antigen , Tetanus Toxin (TT) and immunemodulation with IL-2, IL-12 and anti IL-10 ( antibody mononuclear), marking of intracellular cytokine essay and flow cytometric evaluation...