Jorge Botero

A preliminary study of the prevalence of intestinal parasites in immunocompromised patients with and without gastrointestinal manifestations

The objective of the present study was to determine the prevalence of the intestinal parasites most commonly found in immunocompromised patients. A group of 111 individuals with acute lymphoid leukaemia (ALL), chronic myeloid leukaemia (CML), human immunodeficiency virus (HIV) and other immunocompromised conditions (principally haematological disorders) was selected. A battery of tests was performed on each individual to identify the presence of parasites (three stool specimens with saline solution and Lugol both directly and by concentration, culture and special staining). No significant differences were found among the frequencies of the different parasites with the several types of immunocompromised conditions. The overall frequencies of potentially pathogenic and opportunistic parasites were 32.4% (36/111) and 9% (10/111) respectively, the most frequently encountered among the latter being Cryptosporidium sp., Microsporidia spp. and Strongyloides stercoralis.

Molecular analysis of chronic granulomatous disease caused by defects in gp91-phox

Chronic granulomatous disease (CGD) is an uncommon inherited disorder of phagocytic cells in which a defective respiratory burst leads to severe recurrent bacterial and fungal infections. The disease is a consequence of mutations in one of the four molecules that constitute the NADPH oxidase system of electron transport, whose most critical component is an unusual flavocytochrome b localized in the plasma and specific granule membranes. Mutations in the CYBB gene (localized in the short arm of the X chromosome) encoding the β‐subunit of this flavocytochrome (gp91‐phox), which is are responsible for 60‐65% of all cases of CGD. In this paper, we report the molecular characterization of seven unrelated kindreds native from Colombia and Brazil with CGD caused by gp91‐phox deficiency. The exons with the possible mutation were identified by single‐strand conformational polymorphism (SSCP) of genomic DNA and then confirmed by DNA sequencing. In one patient we found a substitution of A to G in the penultimate nucleotide of intron 12 (IVS12‐2A→G). In four other cases, four different nonsense mutations were detected: R91X, W106X, R157X, and R290X and the other two patients showed missense substitutions: E225V and C244Y. In six of these kindreds, all mothers were carriers but one that did not present any change in the gp91‐phox gene, which indicates a de novo mutation in this kindred. Then, these family‐specific mutations in gp91‐phox produce different structural defects that alter the expression or function of an essential component of phagocyte oxidase. Hum Mutat 13:29–37, 1999.

Broad histopathologic patterns of non-glabrous skin and glabrous skin from patients with a new variant of endemic pemphigus foliaceus-part 1

A prospective, controlled epidemiologic survey performed in El Bagre, Colombia revealed a new variant of endemic pemphigus disease, occurring in a gold mining region. The disease resembled Senear‐Usher syndrome, and occurred in an endemic fashion. The aim of this study is to describe the most frequent histopathologic patterns in non‐glabrous skin and in glabrous skin observed in these patients, and their clinical correlation. The study was performed on non‐glabrous skin biopsies of 30 patients from the dominantly clinical affected areas (either on the chest, arms or face). Simultaneously, biopsies from the palms were obtained in 10 randomly chosen patients of the 30 total patients. The specimens were examined following hematoxylin and eosin (H&E) staining. The most common blisters observed were subcorneal, although in some cases intraspinous and subepidermal blisters were visualized. Our results showed a very heterogeneous pattern of histopathologic patterns in non‐glabrous skin, which seemed to correlate with the clinical features. The most common pattern was typical pemphigus foliaceus‐like, with some lupus erythematosus‐like features. A non‐specific, chronic dermatitis pattern prevailed in the clinically controlled patients taking daily corticosteroids. In the patients who have had the most severe and relapsing pemphigus, early sclerodermatous changes and scleredermoid alterations prevailed in their reticular dermis. In addition to the scleredermoid alterations, the reticular dermis showed a paucity of appendageal structures. On the contrary, in the palms, a similar pattern was seen in all cases, including thickening of the stratum corneum, hypergranulosis, edema in the papillary and reticular dermis and a dermal perivascular lymphocytic infiltrate. The direct immunofluorescence of the glabrous vs. the non‐glabrous skin also showed some differences. We conclude that the histopathologic features of this new variant of endemic pemphigus are complex, therefore, classical histopathologic features previously described for superficial, endemic pemphigus cannot be used alone to diagnose this disease.

Heparin plus aspirin as a "single" therapy for recurrent spontaneous abortion associated with both allo- and autoimmunity.

PROBLEM: The aim of this study was to contribute to the study of the pathogenesis and the treatment of recurrent spontaneous abortion (RSA) associated with immune alterations.

The production of MLR-blocking factors after lymphocyte immunotherapy for RSA does not predict the outcome of pregnancy.

PROBLEM: The questions of whether production of mixed lymphocyte reaction‐blocking factors (MLR‐BFs) after immunotherapy with lymphocytes for recurrent spontaneous abortion (RSA) has prognostic value and whether cytotoxic antibodies are also involved were tested.

Encephalitozoon intestinalis Inhibits Dendritic Cell Differentiation through an IL-6-Dependent Mechanism

Microsporidia are a group of intracellular pathogens causing self-limited and severe diseases in immunocompetent and immunocompromised individuals, respectively. A cellular type 1 adaptive response, mediated by IL-12, IFNγ, CD4+, and CD8+ T cells has been shown to be essential for host resistance, and dendritic cells (DC) play a key role at eliciting anti-microsporidial immunity. We investigated the in vitro response of DC and DC precursors/progenitors to infection with Encephalitozoon intestinalis (Ei), a common agent of human microsporidosis. Ei-exposed DC cultures up-regulated the surface expression of MHC class II and the costimulatory molecules CD86 and CD40, only when high loads of spores were used. A vigorous secretion of IL-6 but not of IL-1β or IL-12p70 was also observed in these cultures. Ei-exposed DC cultures consisted of immature infected and mature bystander DC, as assessed by MHC class II and costimulatory molecules expression, suggesting that intracellular Ei spores deliver inhibitory signals in DC. Moreover, Ei selectively inhibited the secretion of IL-12p70 in LPS-stimulated DC. Whereas Ei-exposed DC promoted allogeneic naïve T cell proliferation and IL-2 and IFNγ secretion in DC-CD4+ T cell co-cultures, separated co-cultures with bystander or infected DCs showed stimulation or inhibition of IFNγ secretion, respectively. When DC precursors/progenitors were exposed to Ei spores, a significant inhibition of DC differentiation was observed without shifting the development toward cells phenotypically or functionally compatible with myeloid-derived suppressor cells. Neutralization experiments demonstrated that this inhibitory effect is IL-6-dependent. Altogether this investigation reveals a novel potential mechanism of immune escape of microsporidian parasites through the modulation of DC differentiation and maturation.