Absalom Lima Filgueira

HLA markers in familial Lichen Sclerosus

Background: Lichen sclerosus (LS) has been identified with increased frequency in families,often associated with HLA markers, mainly DQ7. A genetic co‐etiology seems likely in this setting. Moreover, there is an association of LS with autoimmune disorders, such as the presence of anti‐thyroid peroxidase autoantibodies (anti‐TPO), a hallmark of autoimmune thyroid diseases.

Psoriasis vulgaris and human leukocyte antigens.

Background  Psoriasis vulgaris is a skin disease with a complex immunological and genetic background, triggered by environmental factors. The association of human leukocyte antigens (HLA) and psoriasis has long been reported on population and familial studies.

A Morphological and Cytochemical Study of the Interaction between Paracoccidiodes brasiliensis and Neutrophils

Paracoccidioidomycosis is a systemic granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis. It is the most prevalent systemic mycosis of Latin America and 80% of the reported cases are from Brazil. Because of the great number of neutrophils found in the P. brasiliensis granuloma, studies have been done to evaluate the role of these cells during the development of the infection. Scanning and transmission electron microscopy of thin sections showed that the neutrophils ingest yeast cells through a typical phagocytic process with the formation of pseudopodes. The pseudopodes even disrupt the connection established between the mother and the bud cells. Neutrophils also associate to each other, forming a kind of extracellular vacuole where large yeast cells are encapsulated. Cytochemical studies showed that once P. brasiliensis attaches to the neutrophil surface, it triggers a respiratory burst with release of oxygen-derived products. Attachment also triggers neutrophils degranulation, with release of endogenous peroxidase localized in cytoplasmic granules. Together, these processes lead to killing of both ingested and extracellular P. brasiliensis.

Viability of yeast form cells of Paracoccidioides brasiliensis after sonication

To perform in-vitro studies with Paracoccidioides brasiliensis yeast cells it is necessary to avoid the presence of clumps of cells while maintaining their integrity. Because of the multiple budding type of growth, the bud cells are always attached to the mother cell and the yeast cells keep growing, resulting in the formation of large clumps. In order to obtain free cells, the cultures are usually sonicated. The present study shows that sonication induces lesions in a significant number of cells, as evaluated by labelling of the cells with acridine orange and Janus green vital dyes. In some cases labelling was initially observed in only one cell of the clump; however, the other cells also became labelled after a few minutes. These observations were confirmed by scanning and transmission electron microscopy of treated cells. Colony forming units (c.f.u.) on BHI plates also confirmed the decrease in cell viability following sonication.

Manifestações tegumentares da doença enxerto contra hospedeiro em pacientes transplantados de medula óssea

A doenca enxerto contra hospedeiro (DECH) e uma sindrome sistemica que ocorre em pacientes que recebem linfocitos imunocompetentes. A fisiopatologia envolve uma reacao imunologica entre linfocitos transplantados e tecidos do hospedeiro, e ocorre por ataque imune das celulas T do doador as celulas do hospedeiro, as quais diferem daquelas pelos antigenos de histocompatibilidade. E, assim, uma complicacao primaria do transplante de medula ossea (TMO) alogenico. O envolvimento cutâneo e frequente na DECH e contribui para a morbidade e mortalidade do TMO. O dermatologista tem papel importante na avaliacao dos pacientes auxiliando no reconhecimento precoce da DECH e suas complicacoes e no acompanhamento clinico desses pacientes. Nesta revisao os autores enfatizam as manifestacoes cutâneas da DECH, tendo como base sua experiencia pessoal no acompanhamento de pacientes portadores de DECH transplantados de medula ossea no Centro Nacional de Transplante de Medula Ossea/Inca/MS, no Rio de Janeiro, nos ultimos 14 anos.

Correlation between HLA and pityriasis rosea susceptibility in Brazilian blacks.

Objectives  The human leucocyte antigen (HLA) has been related to susceptibility factors in several diseases. This study aimed to determine the potential genetic susceptibility of patients with pityriasis rosea (PR) through HLA molecular typing analysis.

Reduction of skin-homing cytotoxic T cells (CD8+–CLA+) in patients with vitiligo

Background: Vitiligo is a frequently acquired, hereditary disease, characterized by achromic macules due to the absence of melanocytes. In contrast with earlier studies, in which the main pathogenic role was attributed to anti‐melanocyte antibodies, recent papers have emphasized a role for CD8+ cytotoxic T lymphocytes in melanocyte destruction. Fifteen percent of peripheral T cell express cutaneous lymphocyte‐associated antigen (CLA), responsible for skin‐homing T cell. Phototherapy is used to treat patients with generalized vitiligo and it has been shown to interfere with CLA+ T cells in other skin diseases.

Redução dos linfócitos T-CD8+ citotóxicos observada com a terapia Puva em paciente com vitiligo

The role of cytotoxic T cells (CD8+) has been emphasized in the pathogenesis of vitiligo. This cell population, identified by a skin homing molecule (cutaneous lymphocyte associated antigen Â- CLA), has been described in patients with other dermatoses and can be reduced with phototherapy. The authors present the case of a patient with generalized vitiligo and clinical recovery after PUVA parallel to a 25% reduction in CD8+-CLA+ T cells in the peripheral blood.

HLA-Marker bei familiärem Lichen sclerosus

Background: Lichen sclerosus (LS) has been identified with increased frequency in families, often associated with HLA markers, mainly DQ7. A genetic co-etiology seems likely in this setting. Moreover, there is an association of LS with autoimmune disorders, such as the presence of anti-thyroid peroxidase autoantibodies (anti-TPO), a hallmark of autoimmune thyroid diseases. Patients and Methods: In 3 families affected by LS, we verified their HLA markers, and identified previously undiagnosed cases of LS and autoimmune disorders. 30 individuals were examined with history, skin biopsy, HLA class I and II typing by PCR-SSP, and measurement of anti-TPO, free thyroxine and thyroid-stimulating hormones (TSH) levels. Results: There were 8 cases of LS, 50 % of them anti-TPO+. Autoimmune disorders were found in 40 % (total) and in 87.5 % of those affected. Most common HLA markers were B*15, B*57, CW*03, CW*07, CW*18, DRB1*04, DRB1*07, DRB4*.The three latter have been previously associated with LS. Conclusion: New cases of LS and autoimmune disorders can be detected in first degree relatives of patients with LS.The presence of anti-TPO antibodies strongly suggests autoimmune thyroiditis. There is intra-familial association between the haplotype HLA-B*15 -DRB1*04 -DRB4* and anti-TPO, emphasizing their link with thyroiditis. New familial approaches might help to make clear the pathogenesis of LS and its association with autoimmune diseases.

Primary cutaneous T cell lymphomas: photochemotherapy immunomodulation with analysis of the inflammatory‐expansive cellular dynamic

Primary cutaneous T cell lymphomas (CTCLs) are characterized by hyperproliferation of malignant CD4+ T cells with primary localization on the skin. The common characteristics are the migration of the malignant mature T‐lymphocytes into the epidermis, with hyperproliferation of malignant CD4+ T cells and epidermotropism. Sézary syndrome (SS) is the leukemic variant. It was established that CTCLs arise from a clonal expansion of CD4+ T cells with an identical rearrangement of the T cell receptor. The purpose of this study was to evaluate the immunomodulation effect of photochemotherapy‐A (psoralen plus ultraviolet A (PUVA)). Pre‐ and post‐PUVA punch skin biopsies of nine patients were stained immunohistochemically for CD34+, CD8+, CD7+, CD16+, CD56+, CD1a+, Bcl2+, p53+, CD45RA+, and CD45RO+ cells. The results showed a pre‐PUVA cells/mm2 without significant difference among expansive or reactive cells. Post‐PUVA analysis showed a significant decrease in the mean of expansive‐reactive cells. PUVA immunomodulated decreasing cellular infiltrate. These findings could contribute to the comprehension of how PUVA acts. We achieved ectoscopic clearance of the lesions, although post‐PUVA, there still was a mononuclear pathological infiltrate. This result demonstrates that the PUVA treatment should only be withheld when the histological analysis is normal.