Esophageal mucosa in HIV infection: A"deeper" look at this little spoken organ.

BACKGROUND AND AIM: Although the esophagus is a common site of opportunistic infection in AIDS patients, little is known about the impact of HIV as well as opportunistic infection in the esophageal mucosa. Our aim is to analyze the esophageal immune profile in HIV+ patients with different immunological status with and without the opportunistic Candida infection. METHODS: Immunohistochemistry to CD4+ and CD8+ T-cells, γ-interferon, transforming growth factor-ß, interleukin (IL)-4, IL-6, IL-13, and IL-17 was performed in esophageal samples of 40 chronically HIV+ patients under highly active antiretroviral therapy (16 with Candida esophagitis, 12 virologically non-supressed with blood CD4 count < 500, and 12 virologically suppressed with blood CD4 count > 500; the latter two groups without esophageal candidiasis). The controls were 12 HIV-negative healthy individuals. RESULTS: Esophageal CD4+ T-cell expression in HIV+ patients did not differ from the control group (P = 0.50). Mucosal CD8+ T-cell expression was significantly increased in HIV+ patients (P = 0.0018). Candida esophagitis and virologically non-supressed HIV+ patients with CD4 < 500 showed an increased expression of IL-17 and IL-6 with fewer expressions of γ-interferon, more attenuated in the latter group. Transforming growth factor-ß was increased only in virologically suppressed HIV+ patients with CD4 > 500. IL-4 and IL-13 were similar to the control group. CONCLUSION: In contrast to CD8+ T-cell expression, esophageal CD4+ T-cell expression does not reflect the HIV+ patient's immunological status. T-helper 17 (Th17) response seems to play a role in the esophageal mucosa of virologically non-supressed HIV+ patients with blood CD4 < 500. Candida esophagitis showed a Th1/Th17 response but seems to be dominantly regulated by the Th17 pathway.

Pruritic papular eruption associated with HIV-etiopathogenesis evaluated by clinical, immunohistochemical, and ultrastructural analysis.

Pruritic Papular Eruption with Human Immunodeficiency Virus infection (PPE-HIV) is characterized by symmetrically distributed papules with pruritus in the skin of patients suffering advanced HIV infection. Although known since 1985, the etiology of this symptomatic dermatitis is unclear. We set out to characterize the phenotype of the infiltrating cells and the cytokine profile in the lesions, as an attempt to contribute to determining its etiopathogenesis. Clinical data and histological, immunohistochemical, and ultrastructural features of skin biopsies from 20 HIV patients with PPE were studied. The histopathological aspects, cell immunophenotypes, and cytokine expressions in the lesions where quantified and compared to perilesional skin, and to those in the clinically normal skin of HIV patients without PPE-HIV (n=11) and those in normal skin samples from HIV negative individuals (n=10). PPE-HIV occurred mainly in HIV patients with mean CD4+ counts of 124.6 +/- 104 lymphocytes/mm3. Furthermore, their eosinophil counts were significantly increased. The skin lesions were characterized by a predominantly perivascular dermal lymphohistiocytic inflammatory infiltrate. Langerhans cells were normally distributed in the epidermis and seen among the cellular components of dermal infiltrates. The density of CD8+ lymphocytes was elevated and the density of CD4+ cells was reduced in dermal infiltrates. Interleukin 5 was the predominant cytokine in the lesions. Electron microscopic analysis didn't disclose HIV or other infectious agents in the lesions. These results refute the hypothesis of an infectious etiology of PPE-HIV. CD8+ lymphocytes and Langerhans cells seem to have roles in the pathogenesis of PPE-HIV. The increased frequency of IL5 was associated with abundant eosinophils in the lesions, suggesting a type Th2 response in this dermatitis.

Ultrastructural study of the pancreas in AIDS.

INTRODUCTION: Frequent histologic changes (90%) in the pancreas suggesting protein-energy malnutrition were found in a previous necropsy study of pancreas morphology in patients with AIDS. However, additional studies were required to clarify subcellular changes. AIM: To ultrastructurally analyze pancreas changes in AIDS patients through transmission electron microscopy. METHODOLOGY AND RESULTS: Pancreas specimens for necropsy were obtained from nine consecutive AIDS patients and four normal controls. A semiquantitative histologic and ultrastructural analysis of exocrine pancreas was carried out with the following findings: preserved pancreas structure with little autolysis, marked decrease in zymogen granules (100%), increased lipofuscin pigment (80%), augmented and dilated rough endoplasmic reticulum (100%), and increased number and size of mitochondria. The Golgi complex could be identified only in two cases. In all cases, acinar nuclei were decreased in size, with peripherally condensed chromatin and undulated membrane suggesting early apoptosis. In addition, immunohistochemical evaluation of the pancreas was carried out to detect opportunistic agents. CONCLUSION: Decreased zymogen granules, acinar atrophy, increased lipofuscin pigment, and rarefying Golgi complex represent the morphologic substrate of protein-energy malnutrition in AIDS patients. The combination of rough endoplasmic reticulum and mitochondria changes could be due to the need for supplying vital plasma proteins rather than exportation protein synthesis associated, or not, with the deleterious effects of inflammatory cytokines and/or therapy for disease.