HIV-2 infection is associated with preserved GALT homeostasis and epithelial integrity despite ongoing mucosal viral replication.

The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per µl) despite their undetectable viremia, accompanied by interferon-γ-producing CD8 T-cell expansion, irrespective of antiretroviral treatment. Nevertheless, there was no CD4 T-cell depletion, and Foxp3+ and IL-17- or IL-22-producing CD4 T-cell numbers were unaffected. Moreover, IL-22-producing innate lymphoid cells and IL-22-induced antimicrobial peptides and mucins were maintained. In agreement, the epithelium histology was preserved, including tight junction protein zonula occludens (ZO-1) levels. Furthermore, in vitro infection of colon epithelia with primary isolates revealed no HIV-2 impact on ZO-1 expression. Notably, sigmoid transcriptional levels of CCL20 and CCL28 were significantly increased, in direct correlation with GM-CSF, indicating a local response able to enhance CD4 T-cell recruitment. In conclusion, maintenance of mucosal integrity in HIV-2 infection was associated with T-cell recruitment responses, potentially counteracting CD4 T-cell depletion due to HIV-2 replication. These data have unique implications for the design of therapies targeting gut homeostasis in HIV-1 infection and other chronic inflammatory settings.

[Immune reconstitution inflammatory syndrome related with infliximab interruption in patient with Crohn's disease and active tuberculosis]. / Síndrome de reconstituição imune associado à interrupção do infliximab em doente com doença de Crohn e tuberculose activa.

Tumor necrosis factor alpha inhibitors are associated with an increased risk of active tuberculosis. However, its interruption in this setting may trigger a paradoxical response to tuberculosis treatment, as an immune reconstitution inflammatory syndrome. We present the case of a 36-year-old patient, with Crohn's disease, treated with infliximab for the last 8 years, who was admitted with miliary tuberculosis. A pan-susceptible Mycobacterium tuberculosis strain was isolated. Infliximab was interrupted and standard antituberculous therapy was started, as well as systemic corticotherapy, without any clinical or radiological improvement. After exclusion of other opportunistic infections and primary or acquired immunodeficiency, we considered the possibility of an immune reconstitution inflammatory syndrome triggered by infliximab interruption. Thus, infliximab was reintroduced after 2 months of antituberculous therapy and clinical and radiological improvement was observed.

[Vasculitis associated with ANCA]. / Vasculites associadas ao ANCA.

The authors present a case report of a 62-year old woman, with hypertension for many years. She suffered from weakness, anorexia and weight loss in the last 6 months. On admission, anemia, elevated ESR, haematuria, proteinuria and renal failure were present. Renal biopsy was compatible with chronic glomerulonephritis. The clinical picture and positivity for P-ANCA suggested systemic vasculitis. Later evidence of maxillary sinusitis and nasal mucosae ulcers as well as pneumonitis, although biopsy did not reveal granulomas, suggested the diagnosis of Wegener Vasculitis. Medicated with Cyclophosphamide and Prednisolone, for a year, with improvement. The authors make a brief discussion of the clinical criteria for classification of ANCA-associated systemic vasculitis.